GeneBe

ASH2L

protein-coding

ASH2 like, histone lysine methyltransferase complex subunit, the group of PHD finger proteins|WRAD complex

Gene summary

Enables beta-catenin binding activity and transcription cis-regulatory region binding activity. Involved in positive regulation of cell population proliferation; response to estrogen; and transcription initiation-coupled chromatin remodeling. Acts upstream of or within DNA damage response. Located in nucleoplasm and plasma membrane. Part of MLL3/4 complex and Set1C/COMPASS complex. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:
  • ASH2L1

MANE transcript

NM_004674.5

Inheritance

—

ClinVar variants

P:1U:74B:2

Top phenotype

Global developmental delay

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr8:38,105,493-38,144,076

External References & Databases

Ensembl (ENSG00000129691)NCBI Gene (9070)OMIM (604782)HGNC:744GenCCUniProt (Q9UBL3)AlphaFoldClinVar (ASH2L)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~38.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ASH2L variants in ClinVar

4 Conditions Cataloged
not specifiedTotal: 63
not providedTotal: 3
Global developmental delayTotal: 1
Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004674.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
 2
missense
1
clinvar
65
clinvar
2
clinvar
 68
nonsense
1
clinvar
 1
start loss
0
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
4
clinvar
 4
Total01742077

Highest pathogenic variant AF is 6.841368e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 79 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_004674.5RefSeqNP_004665.216MANE Select
ENST00000343823.11EnsemblENSP00000340896.516MANE Select
NM_001105214.2RefSeqNP_001098684.114Standard
NM_001261832.1RefSeqNP_001248761.113Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Cushing,s syndrome - Homo sapiens (human)
  • miR-targeted genes in lymphocytes - TarBase
  • miR-targeted genes in muscle cell - TarBase
  • Signaling by WNT
  • Signal Transduction

Biological Process

  • transcription, DNA-templated
  • regulation of transcription, DNA-templated
  • cellular response to DNA damage stimulus
  • positive regulation of cell population proliferation
  • hemopoiesis

Molecular Function

  • protein binding
  • beta-catenin binding
  • histone-lysine N-methyltransferase activity
  • histone methyltransferase activity (H3-K4 specific)
  • transcription regulatory region DNA binding

Cellular Component

  • nucleus
  • nucleoplasm
  • nuclear euchromatin
  • histone methyltransferase complex
  • MLL3/4 complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000343823
Coding exons
16
Length
38835
Individuals with no LoFs
125739
Homozygous LoFs
0
Heterozygous LoFs
8
Defined
125747
p
0.0000318
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.781993440.5790.00001804090
Missense (PolyPhen)3498.6230.344751116
Synonymous1.091121280.8770.000007201172
Loss of Function5.12336.30.08260.00000195436

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.0000910.000087rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000350.000035rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Component of the Set1/Ash2 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3, but not if the neighboring 'Lys-9' residue is already methylated. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. May function as a transcriptional regulator. May play a role in hematopoiesis. {ECO:0000269|PubMed:12670868, ECO:0000269|PubMed:19556245}.;

Recessive Scores

pRec
0.117

Intolerance Scores

LoFtool
0.296
RVIS EVS
-0.27
RVIS percentile EVS
34.6

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
S
Essential (gene trap)
H
Indispensability pred.
E
Indispensability score
0.891

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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