{
  "title": "ASH1L Tissue Biology Data",
  "gene": {
    "symbol": "ASH1L",
    "ensemblGeneId": "ENSG00000116539",
    "ncbiGeneId": "55870"
  },
  "sourceCheckedOn": "2026-07-22",
  "interpretationNote": "Normal-reference RNA abundance is not protein activity, altered variant dosage, tissue vulnerability, phenotype prevalence, or treatment evidence. Bulk tissue, single-cell RNA, immune-cell RNA, tissue-cell enrichment, and deep visual proteomics remain distinct modalities.",
  "source": {
    "name": "Human Protein Atlas ASH1L gene page with HPA/GTEx consensus RNA display",
    "sourceNote": "Source page checked 2026-07-22.",
    "sourceSnapshot": {
      "hpaRelease": "25.1",
      "ensemblRelease": "109",
      "accessedOn": "2026-07-22",
      "releaseHistoryUrl": "https://www.proteinatlas.org/about/releases"
    },
    "urls": [
      "https://www.proteinatlas.org/ENSG00000116539-ASH1L",
      "https://gtexportal.org/home/gene/ENSG00000116539"
    ],
    "upstreamConsensusTissueCount": 51,
    "expressionRowCount": 51,
    "coverageNote": "This dataset includes all 51 tissues in the cited HPA/GTEx consensus RNA file. Other HPA modalities and tissue labels are separate datasets and are not treated as missing consensus values."
  },
  "cellClasses": [
    {
      "label": "Neural & glial",
      "cells": "Brain-region single-cell types and separate deep-visual-proteomics categories",
      "reading": "The brain-region atlas includes neurons, astrocytes, Bergmann glia, oligodendroglial lineages, microglia, and vascular cells. Separate DVP categories include neurons, astrocytes/neuropil, and microglia/neuropil; those modalities are not one cell-level measurement.",
      "modality": "HPA brain-region single-cell atlas plus separately reported deep visual proteomics categories",
      "cellClassNumber": 1,
      "sources": [
        "Human Protein Atlas ASH1L page"
      ]
    },
    {
      "label": "Airway & epithelial",
      "cells": "Ciliated cells, alveolar type 1 and type 2 cells, keratinocytes, secretory cells, and pancreatic epithelial cells",
      "reading": "Detection identifies cell contexts for experiments; it does not establish epithelial disease in ASH1L haploinsufficiency.",
      "modality": "HPA single-cell and tissue-cell expression context",
      "cellClassNumber": 2,
      "sources": [
        "Human Protein Atlas ASH1L page"
      ]
    },
    {
      "label": "Metabolic & renal",
      "cells": "Hepatocytes, pancreatic islets, glomerular cells, proximal and distal tubules, and collecting ducts",
      "reading": "Human atlas detection is broad. Direct germline loss-of-function mechanisms in these lineages remain largely untested.",
      "modality": "HPA single-cell and tissue-cell expression context",
      "cellClassNumber": 3,
      "sources": [
        "Human Protein Atlas ASH1L page"
      ]
    },
    {
      "label": "Muscle & vascular",
      "cells": "Cardiomyocytes, skeletal myofibers, capillaries, smooth-muscle cells, and vascular support cells",
      "reading": "Human expression is supported; direct functional evidence is strongest for myoblast fusion in a mouse/cell model.",
      "modality": "HPA single-cell and tissue-cell expression context",
      "cellClassNumber": 4,
      "sources": [
        "Human Protein Atlas ASH1L page"
      ]
    },
    {
      "label": "Reproductive",
      "cells": "Granulosa cells, oocytes, spermatocytes, and reproductive-tract cell populations",
      "reading": "HPA predicts enrichment in spermatocytes and adrenal-cortex cells. A mouse fetal-ovary overexpression study is a dosage-perturbation model, not a germline loss-of-function result.",
      "modality": "HPA single-cell and tissue-cell expression context",
      "cellClassNumber": 5,
      "sources": [
        "Human Protein Atlas ASH1L page"
      ]
    },
    {
      "label": "Immune",
      "cells": "Neutrophils, macrophages, CD4 and CD8 T cells, B cells, dendritic cells, and other blood lineages",
      "reading": "Human immune-cell RNA has low specificity. Mouse macrophage and T-cell studies supply direct lineage mechanisms, but not a human ASH1L immune phenotype.",
      "modality": "HPA single-cell and immune-cell RNA context",
      "cellClassNumber": 6,
      "sources": [
        "Human Protein Atlas ASH1L page"
      ]
    }
  ],
  "stateTransitionEvidence": [
    {
      "level": "Neural progenitor",
      "direct": "Arrayed ASH1L knockout increased the proportion of Ki-67-positive progenitors.",
      "limit": "This supports altered proliferative state; it does not directly prove a universal failure of neuronal differentiation.",
      "hrefs": [
        [
          "Primary study",
          "https://www.nature.com/articles/s41593-026-02247-7"
        ]
      ],
      "transitionNumber": 1,
      "evidenceLibrarySourceNumbers": [
        1
      ]
    },
    {
      "level": "Hematopoietic stem cell",
      "direct": "Ash1l-deficient cells failed to establish the normal quiescent adult stem-cell pool.",
      "limit": "Fetal Sox17 and Lin28b programs were still extinguished, so the experiment does not show persistence of a global fetal state.",
      "hrefs": [
        [
          "Primary study",
          "https://www.jci.org/articles/view/78124"
        ]
      ],
      "transitionNumber": 2,
      "evidenceLibrarySourceNumbers": [
        43
      ]
    },
    {
      "level": "Epidermis",
      "direct": "Ash1l disruption altered the proliferation–differentiation balance, stratification, and wound re-epithelialization.",
      "limit": "A hypomorphic mouse-skin result is not proof of a shared human wound-healing mechanism.",
      "hrefs": [
        [
          "Primary study",
          "https://www.nature.com/articles/srep45401"
        ]
      ],
      "transitionNumber": 3,
      "evidenceLibrarySourceNumbers": [
        38
      ]
    },
    {
      "level": "Immune lineages",
      "direct": "Separate models show roles in macrophage inflammatory restraint and induced regulatory-T-cell polarization.",
      "limit": "They do not establish one human immune phenotype, occult inflammation, or immune-directed treatment.",
      "hrefs": [
        [
          "Macrophage model",
          "https://doi.org/10.1016/j.immuni.2013.08.016"
        ],
        [
          "Regulatory T-cell model",
          "https://www.nature.com/articles/ncomms15818"
        ]
      ],
      "transitionNumber": 4,
      "evidenceLibrarySourceNumbers": [
        45,
        39
      ]
    },
    {
      "level": "Muscle and bone",
      "direct": "Experimental studies connect Ash1l to myoblast fusion and osteoclast differentiation or resorption.",
      "limit": "These models do not establish that human weakness, hypermobility, fractures, or low bone density share one cause.",
      "hrefs": [
        [
          "Myoblast model",
          "https://www.nature.com/articles/s41467-018-07313-8"
        ],
        [
          "Osteoclast model",
          "https://pubmed.ncbi.nlm.nih.gov/38431690/"
        ]
      ],
      "transitionNumber": 5,
      "evidenceLibrarySourceNumbers": [
        37,
        15
      ]
    },
    {
      "level": "Memory circuit",
      "direct": "ASH1L was required for later stabilization of selected memories in one thalamocortical mouse task.",
      "limit": "This is maintenance in a defined circuit—not evidence of global human regression or neurodegeneration.",
      "hrefs": [
        [
          "Primary study",
          "https://www.nature.com/articles/s41586-025-09774-6"
        ]
      ],
      "transitionNumber": 6,
      "evidenceLibrarySourceNumbers": [
        2
      ]
    }
  ],
  "tissueSystems": [
    {
      "system": "Brain & eye",
      "note": "Central nervous system, choroid plexus, and retina",
      "systemNumber": 1,
      "tissues": [
        {
          "name": "Cerebral cortex",
          "ntpm": 26.4,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 1
        },
        {
          "name": "Cerebellum",
          "ntpm": 34.5,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 2
        },
        {
          "name": "Basal ganglia",
          "ntpm": 23.9,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 3
        },
        {
          "name": "Hypothalamus",
          "ntpm": 19,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 4
        },
        {
          "name": "Midbrain",
          "ntpm": 18.6,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 5
        },
        {
          "name": "Amygdala",
          "ntpm": 21,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 6
        },
        {
          "name": "Choroid plexus",
          "ntpm": 7.5,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 7
        },
        {
          "name": "Hippocampal formation",
          "ntpm": 21,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 8
        },
        {
          "name": "Spinal cord",
          "ntpm": 17.5,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 9
        },
        {
          "name": "Retina",
          "ntpm": 24.2,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 10
        }
      ]
    },
    {
      "system": "Endocrine",
      "note": "Hormone-producing organs",
      "systemNumber": 2,
      "tissues": [
        {
          "name": "Thyroid gland",
          "ntpm": 17.4,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 11
        },
        {
          "name": "Parathyroid gland",
          "ntpm": 17.1,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 12
        },
        {
          "name": "Adrenal gland",
          "ntpm": 16.2,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 13
        },
        {
          "name": "Pituitary gland",
          "ntpm": 17.6,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 14
        }
      ]
    },
    {
      "system": "Respiratory & upper digestive",
      "note": "Airway and proximal oral–digestive tissues",
      "systemNumber": 3,
      "tissues": [
        {
          "name": "Lung",
          "ntpm": 15.4,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 15
        },
        {
          "name": "Salivary gland",
          "ntpm": 17.7,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 16
        },
        {
          "name": "Esophagus",
          "ntpm": 16.5,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 17
        },
        {
          "name": "Tongue",
          "ntpm": 22.7,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 18
        }
      ]
    },
    {
      "system": "Gastrointestinal tract",
      "note": "Luminal digestive organs",
      "systemNumber": 4,
      "tissues": [
        {
          "name": "Stomach",
          "ntpm": 17.1,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 19
        },
        {
          "name": "Duodenum",
          "ntpm": 9.2,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 20
        },
        {
          "name": "Small intestine",
          "ntpm": 17.1,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 21
        },
        {
          "name": "Colon",
          "ntpm": 23.9,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 22
        },
        {
          "name": "Rectum",
          "ntpm": 10.8,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 23
        }
      ]
    },
    {
      "system": "Liver, gallbladder & pancreas",
      "note": "Metabolic, biliary, exocrine, and endocrine compartments",
      "systemNumber": 5,
      "tissues": [
        {
          "name": "Liver",
          "ntpm": 12.8,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 24
        },
        {
          "name": "Gallbladder",
          "ntpm": 8.5,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 25
        },
        {
          "name": "Pancreas",
          "ntpm": 16.5,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 26
        }
      ]
    },
    {
      "system": "Kidney & urinary tract",
      "note": "Renal and bladder tissue",
      "systemNumber": 6,
      "tissues": [
        {
          "name": "Kidney",
          "ntpm": 13.2,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 27
        },
        {
          "name": "Urinary bladder",
          "ntpm": 21.3,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 28
        }
      ]
    },
    {
      "system": "Male reproductive",
      "note": "Gonadal and reproductive tract tissues",
      "systemNumber": 7,
      "tissues": [
        {
          "name": "Testis",
          "ntpm": 11,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 29
        },
        {
          "name": "Epididymis",
          "ntpm": 19.6,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 30
        },
        {
          "name": "Seminal vesicle",
          "ntpm": 14.5,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 31
        },
        {
          "name": "Prostate",
          "ntpm": 17.4,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 32
        }
      ]
    },
    {
      "system": "Female reproductive & breast",
      "note": "Gonadal, reproductive, placental, and breast tissues",
      "systemNumber": 8,
      "tissues": [
        {
          "name": "Vagina",
          "ntpm": 18,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 33
        },
        {
          "name": "Ovary",
          "ntpm": 24.5,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 34
        },
        {
          "name": "Fallopian tube",
          "ntpm": 17.7,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 35
        },
        {
          "name": "Endometrium",
          "ntpm": 20.7,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 36
        },
        {
          "name": "Cervix",
          "ntpm": 19.2,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 37
        },
        {
          "name": "Placenta",
          "ntpm": 9.7,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 38
        },
        {
          "name": "Breast",
          "ntpm": 18.5,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 39
        }
      ]
    },
    {
      "system": "Muscle & vascular",
      "note": "Cardiac, skeletal, smooth-muscle, and vessel tissue",
      "systemNumber": 9,
      "tissues": [
        {
          "name": "Blood vessel",
          "ntpm": 27.4,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 40
        },
        {
          "name": "Heart muscle",
          "ntpm": 18.5,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 41
        },
        {
          "name": "Smooth muscle",
          "ntpm": 11.9,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 42
        },
        {
          "name": "Skeletal muscle",
          "ntpm": 33.7,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 43
        }
      ]
    },
    {
      "system": "Connective, adipose & skin",
      "note": "Barrier and soft-tissue compartments",
      "systemNumber": 10,
      "tissues": [
        {
          "name": "Adipose tissue",
          "ntpm": 19.3,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 44
        },
        {
          "name": "Skin",
          "ntpm": 20.9,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 45
        }
      ]
    },
    {
      "system": "Bone marrow & lymphoid",
      "note": "Hematopoietic and immune-organ tissues",
      "systemNumber": 11,
      "tissues": [
        {
          "name": "Appendix",
          "ntpm": 8,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 46
        },
        {
          "name": "Spleen",
          "ntpm": 13.9,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 47
        },
        {
          "name": "Lymph node",
          "ntpm": 10.2,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 48
        },
        {
          "name": "Tonsil",
          "ntpm": 9.1,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 49
        },
        {
          "name": "Bone marrow",
          "ntpm": 11.2,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 50
        },
        {
          "name": "Thymus",
          "ntpm": 11.3,
          "unit": "nTPM",
          "measurementScope": "normal reference tissue",
          "patientSpecific": false,
          "sourceStatus": "Shown on the cited ASH1L HPA/GTEx consensus RNA chart on 2026-07-22.",
          "tissueNumber": 51
        }
      ]
    }
  ],
  "functionalEvidence": [
    {
      "tissue": "Human neural cell states",
      "model": "hiPSC-derived neural progenitors; immature and mature glutamatergic neurons; mature GABAergic neurons",
      "result": "Pooled CRISPR knockout showed that ASH1L-associated transcriptional consequences depend on developmental stage and neuronal identity.",
      "href": "https://www.nature.com/articles/s41593-026-02247-7",
      "source": "Fernandez Garcia et al., 2026",
      "strength": "Human cell model",
      "doi": "10.1038/s41593-026-02247-7",
      "species": "human",
      "perturbationDirection": "complete knockout",
      "sourceLocator": "https://www.nature.com/articles/s41593-026-02247-7",
      "modelSourceNumber": 1,
      "evidenceLibrarySourceNumber": 1,
      "interpretationLimit": "Complete knockout in engineered cells does not measure residual function from an individual patient variant."
    },
    {
      "tissue": "Developing brain",
      "model": "Neural-progenitor deletion in mice",
      "result": "Ash1l loss altered cortical development, progenitor programs, myelination, growth, and later behavioral and memory measures in the tested model.",
      "href": "https://www.nature.com/articles/s42003-021-02282-z",
      "source": "Gao et al., 2021",
      "strength": "Direct in vivo",
      "doi": "10.1038/s42003-021-02282-z",
      "species": "mouse",
      "perturbationDirection": "lineage deletion",
      "sourceLocator": "https://www.nature.com/articles/s42003-021-02282-z",
      "modelSourceNumber": 2,
      "evidenceLibrarySourceNumber": 27,
      "interpretationLimit": "A neural-lineage mouse deletion does not establish cell autonomy in every brain lineage or reproduce the full human disorder."
    },
    {
      "tissue": "Prefrontal cortex",
      "model": "Region-specific Ash1l knockdown in mice",
      "result": "The perturbation altered promoter chromatin and synaptic-gene transcription, shifted excitation/inhibition balance, and produced seizure phenotypes.",
      "href": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8593046/",
      "source": "Qin et al., 2021",
      "strength": "Direct in vivo",
      "doi": "10.1038/s41467-021-26972-8",
      "species": "mouse",
      "perturbationDirection": "region-specific knockdown",
      "sourceLocator": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8593046/",
      "modelSourceNumber": 3,
      "evidenceLibrarySourceNumber": 28,
      "interpretationLimit": "A regional knockdown cannot define every cell type, variant architecture, or human seizure trajectory."
    },
    {
      "tissue": "Thalamocortical memory circuit",
      "model": "Targeted CRISPR perturbation in a mouse memory task",
      "result": "ASH1L was required later in the tested cascade to maintain memories over weeks, while initial memory formation was preserved.",
      "href": "https://www.nature.com/articles/s41586-025-09774-6",
      "source": "Terceros et al., 2026",
      "strength": "Direct in vivo",
      "doi": "10.1038/s41586-025-09774-6",
      "species": "mouse",
      "perturbationDirection": "targeted CRISPR perturbation",
      "sourceLocator": "https://www.nature.com/articles/s41586-025-09774-6",
      "modelSourceNumber": 4,
      "evidenceLibrarySourceNumber": 2,
      "interpretationLimit": "This is circuit- and task-specific evidence; it does not define a person’s memory profile or prove progressive decline."
    },
    {
      "tissue": "Macrophage / innate immune",
      "model": "Macrophage and inflammatory mouse models",
      "result": "Ash1l promoted A20/Tnfaip3 expression and restrained TLR-triggered NF-κB/MAPK signaling and IL-6/TNF production in the tested models.",
      "href": "https://doi.org/10.1016/j.immuni.2013.08.016",
      "source": "Xia et al., 2013",
      "strength": "Direct lineage model",
      "doi": "10.1016/j.immuni.2013.08.016",
      "species": "mouse",
      "perturbationDirection": "conditional loss",
      "sourceLocator": "https://doi.org/10.1016/j.immuni.2013.08.016",
      "modelSourceNumber": 5,
      "evidenceLibrarySourceNumber": 45,
      "interpretationLimit": "This does not establish immune deficiency, autoimmunity, or hidden inflammation in people with ASH1L-related disorder."
    },
    {
      "tissue": "CD4 T-cell differentiation",
      "model": "Mouse T-cell polarization with human rheumatoid-arthritis correlation",
      "result": "Ash1l and lnc-Smad3 oppositely regulated Smad3-locus accessibility and induced regulatory T-cell polarization.",
      "href": "https://www.nature.com/articles/ncomms15818",
      "source": "Xia et al., 2017",
      "strength": "Direct lineage model",
      "doi": "10.1038/ncomms15818",
      "species": "mouse with human correlation",
      "perturbationDirection": "lineage perturbation",
      "sourceLocator": "https://www.nature.com/articles/ncomms15818",
      "modelSourceNumber": 6,
      "evidenceLibrarySourceNumber": 39,
      "interpretationLimit": "The study concerns immune-lineage regulation and autoimmunity models, not ASH1L neurodevelopmental-disorder prevalence."
    },
    {
      "tissue": "Hematopoietic stem cells",
      "model": "Conditional Ash1l deletion in mouse hematopoietic stem and progenitor cells",
      "result": "Ash1l supported adult stem-cell quiescence, long-term trilineage hematopoiesis, and Hox-gene expression in the tested system.",
      "href": "https://www.jci.org/articles/view/78124",
      "source": "Jones et al., 2015",
      "strength": "Direct lineage model",
      "doi": "10.1172/jci78124",
      "species": "mouse",
      "perturbationDirection": "conditional deletion",
      "sourceLocator": "https://www.jci.org/articles/view/78124",
      "modelSourceNumber": 7,
      "evidenceLibrarySourceNumber": 43,
      "interpretationLimit": "Stem-cell lineage biology does not establish blood-count abnormalities, immune deficiency, or leukemia risk in ASH1L-related disorder."
    },
    {
      "tissue": "Epidermis / keratinocytes",
      "model": "Hypomorphic Ash1l mouse skin",
      "result": "Ash1l disruption altered keratinocyte proliferation–differentiation balance, epidermal stratification, and wound re-epithelialization.",
      "href": "https://www.nature.com/articles/srep45401",
      "source": "Li et al., 2017",
      "strength": "Direct tissue model",
      "doi": "10.1038/srep45401",
      "species": "mouse",
      "perturbationDirection": "hypomorphic disruption",
      "sourceLocator": "https://www.nature.com/articles/srep45401",
      "modelSourceNumber": 8,
      "evidenceLibrarySourceNumber": 38,
      "interpretationLimit": "This supports a skin-homeostasis mechanism in mice; it does not establish a universal human skin phenotype."
    },
    {
      "tissue": "Neuronal–cutaneous inflammatory axis",
      "model": "Ash1l perturbation in a mouse psoriasis model",
      "result": "Neuronal Ash1l altered activity-dependent let-7b release and downstream cutaneous inflammatory signaling in the tested disease model.",
      "href": "https://doi.org/10.1111/bph.16254",
      "source": "Du et al., 2024",
      "strength": "Cross-tissue model",
      "doi": "10.1111/bph.16254",
      "species": "mouse",
      "perturbationDirection": "neuronal perturbation",
      "sourceLocator": "https://doi.org/10.1111/bph.16254",
      "modelSourceNumber": 9,
      "evidenceLibrarySourceNumber": 16,
      "interpretationLimit": "A psoriasis model does not establish psoriasis, neuroinflammation, or one shared skin mechanism in germline ASH1L haploinsufficiency."
    },
    {
      "tissue": "Skeletal muscle / myoblasts",
      "model": "Mouse myoblasts, developing muscle, and regeneration models",
      "result": "Ash1l activated Cdon and supported myoblast fusion, a process required for muscle formation, growth, and repair.",
      "href": "https://www.nature.com/articles/s41467-018-07313-8",
      "source": "Castiglioni et al., 2018",
      "strength": "Direct tissue model",
      "doi": "10.1038/s41467-018-07313-8",
      "species": "mouse",
      "perturbationDirection": "loss or reduction",
      "sourceLocator": "https://www.nature.com/articles/s41467-018-07313-8",
      "modelSourceNumber": 10,
      "evidenceLibrarySourceNumber": 37,
      "interpretationLimit": "The result does not establish a primary myopathy or explain every motor, tone, fatigue, or recovery finding."
    },
    {
      "tissue": "Bone / osteoclast lineage",
      "model": "Mouse osteoclast differentiation and bone-loss models",
      "result": "ASH1L restrained osteoclastogenesis and bone resorption in the tested models.",
      "href": "https://pubmed.ncbi.nlm.nih.gov/38431690/",
      "source": "Zhao et al., 2024",
      "strength": "Direct tissue model",
      "doi": "10.1038/s41418-024-01274-w",
      "species": "mouse",
      "perturbationDirection": "loss or reduction",
      "sourceLocator": "https://pubmed.ncbi.nlm.nih.gov/38431690/",
      "modelSourceNumber": 11,
      "evidenceLibrarySourceNumber": 15,
      "interpretationLimit": "Human bone fragility or osteoporosis is not established as an ASH1L-related-disorder mechanism."
    },
    {
      "tissue": "Fetal ovary / oocytes",
      "model": "Ash1l overexpression in mouse fetal ovaries",
      "result": "Excess Ash1l was associated with impaired DNA double-strand-break repair signaling and oocyte apoptosis in that model.",
      "href": "https://pubmed.ncbi.nlm.nih.gov/36094439/",
      "source": "Zhang et al., 2022",
      "strength": "Dosage-context model",
      "doi": "10.1152/ajpcell.00196.2022",
      "species": "mouse",
      "perturbationDirection": "overexpression",
      "sourceLocator": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9576165/",
      "modelSourceNumber": 12,
      "evidenceLibrarySourceNumber": 23,
      "interpretationLimit": "The perturbation is overexpression—the opposite direction from haploinsufficiency—and cannot be used to infer fertility risk."
    },
    {
      "tissue": "Heart development",
      "model": "Drosophila cardiac tissue",
      "result": "Ash1 with Caf1-55 and MRG15 supported H3K36me2-dependent heart development in vivo.",
      "href": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10380788/",
      "source": "Zhu et al., 2023",
      "strength": "Distal in vivo model",
      "doi": "10.3390/jcdd10070307",
      "species": "Drosophila",
      "perturbationDirection": "loss or reduction",
      "sourceLocator": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10380788/",
      "modelSourceNumber": 13,
      "evidenceLibrarySourceNumber": 20,
      "interpretationLimit": "A fly developmental result does not establish a human cardiac phenotype or clinical risk."
    }
  ],
  "researchPriorities": [
    {
      "title": "Brain, glia & memory",
      "priorityNumber": 1,
      "description": "Measure allele-specific RNA/protein dosage in neurons and glia across differentiation; separate encoding, stabilization, retrieval, sleep state, and network excitability in human phenotyping.",
      "purpose": "measurement priority"
    },
    {
      "title": "Oral, enteric & GI",
      "priorityNumber": 2,
      "description": "Build oral epithelial, enteric-neuron, smooth-muscle, and intestinal models only alongside objective feeding, motility, growth, or mucosal phenotypes.",
      "purpose": "measurement priority"
    },
    {
      "title": "Immune, skin & barrier",
      "priorityNumber": 3,
      "description": "Pair defined clinical events with immune-cell, epithelial, and recovery assays. Systemic ESR/CRP and tissue-local function are different measurements.",
      "purpose": "measurement priority"
    },
    {
      "title": "Muscle & bone",
      "priorityNumber": 4,
      "description": "Use standardized strength, fatigue, gait, fracture, mineral, and DXA phenotyping where indicated; then connect selected alleles to myoblast and osteoclast assays.",
      "purpose": "measurement priority"
    },
    {
      "title": "Endocrine & reproductive",
      "priorityNumber": 5,
      "description": "Capture puberty, cycle, growth, and endocrine trajectories prospectively before selecting hormone-responsive cell models. Expression alone is not treatment evidence.",
      "purpose": "measurement priority"
    },
    {
      "title": "Cardiac, autonomic & renal",
      "priorityNumber": 6,
      "description": "Start with reproducible human physiology—ECG, vitals, imaging, laboratory, or functional anchors—before assigning tissue-autonomous ASH1L mechanism.",
      "purpose": "measurement priority"
    }
  ],
  "cellularEnergyLevels": [
    {
      "number": "01",
      "title": "Clinical energy context",
      "description": "Fatigue, feeding, illness recovery, exercise tolerance, temperature, or state-sensitive function can motivate ordinary clinical assessment. These observations are nonspecific.",
      "purpose": "measurement level"
    },
    {
      "number": "02",
      "title": "Defined clinical measurement",
      "description": "Blood, urine, nutrition, endocrine, or organ-function studies answer the clinical question and time window for which they were obtained.",
      "purpose": "measurement level"
    },
    {
      "number": "03",
      "title": "Specialized tissue assay",
      "description": "Respiration, membrane potential, enzyme activity, metabolites, or imaging remain attached to the named specimen, method, reference, and state.",
      "purpose": "measurement level"
    },
    {
      "number": "04",
      "title": "Replication",
      "description": "Repeat sampling, an independent laboratory, another relevant tissue, or a validated model asks whether the result is reproducible.",
      "purpose": "measurement level"
    },
    {
      "number": "05",
      "title": "Patient-allele and rescue test",
      "description": "An isogenic model asks whether a specific ASH1L allele produces the readout and whether correction or defined rescue reverses it.",
      "purpose": "measurement level"
    },
    {
      "number": "06",
      "title": "ASH1L-causal inference",
      "description": "Requires convergent evidence across allele, cell identity, state, time, mechanism, and rescue. This level is not currently established.",
      "purpose": "unresolved causal inference"
    }
  ]
}