ASH2L

Chr 8

ASH2 like, histone lysine methyltransferase complex subunit

Also known as: ASH2, ASH2L1, ASH2L2, Bre2

NCBI Gene: 9070 ENSG00000129691 UniProt: Q9UBL3 OMIM: 604782

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.21

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.21LOEUF

pLI 1.000

Z-score 5.12

OE 0.08 (0.04–0.21)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.78Z-score

OE missense 0.58 (0.52–0.65)

199 obs / 343.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.08 (0.04–0.21)

0≤0.351.4

Missense OE?0.58 (0.52–0.65)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 3 / 36.3Missense obs/exp: 199 / 343.8Syn Z: 1.09

Background carrier burden — how many people carry a rare variant somewhere in ASH2L?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

659 rare PASS variants

Rare truncating (LoF)

1 in 3,100

80 rare PASS variants

Rare synonymous (reference)

1 in 230

320 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ASH2L. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 250	1 in 4,800
South Asian	~43k	1 in 82	≈ 1 in 10,000
Remaining (unassigned)	~30k	1 in 140	≈ 1 in 7,400
European (Finnish)	~27k	1 in 270	≈ 1 in 17,000
Admixed American	~22k	1 in 120	1 in 4,000
African / African American	~21k	1 in 140	1 in 1,200
East Asian	~20k	1 in 150	none seen
Ashkenazi Jewish	~13k	1 in 450	none seen
Middle Eastern	~2,884	1 in 92	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 15 of 16 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: 15 of 16 (exon 10 below).? see exons ↓