YEATS2

Chr 3AD

YEATS domain containing 2

Also known as: FAME4

NCBI Gene: 55689 ENSG00000163872 UniProt: Q9ULM3 OMIM: 613373

YEATS2 encodes a chromatin reader component of the ATAC complex that recognizes crotonylated histone H3 and facilitates histone acetyltransferase activity at active promoters and enhancers. Mutations cause familial adult myoclonic epilepsy with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.28), indicating intolerance to haploinsufficiency in the general population.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Summary: The protein encoded by this gene is a scaffolding subunit of the ATAC complex, which is a complex with acetyltransferase activity on histones H3 and H4. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2017]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.281 OMIM phenotype

Clinical Summary— YEATS2

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 188 VUS of 248 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.28LOEUF

pLI 0.996

Z-score 6.56

OE 0.18 (0.11–0.28)

Highly constrained

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

Missense Constraint?

0.97Z-score

OE missense 0.90 (0.85–0.96)

695 obs / 770.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.18 (0.11–0.28)

0≤0.351.4

Missense OE?0.90 (0.85–0.96)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 13 / 73.9Missense obs/exp: 695 / 770.9Syn Z: 1.04

This gene — mechanism propensity

0.2897th %ile

GOF

0.12100th %ile

LOF

0.79top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.28

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

248 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS188

Likely Benign17

Benign7

Conflicting2

Pathogenic

188

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	1	0	1
Likely Pathogenic	0	0	0	0	0
VUS	1	187	0	0	188
Likely Benign	1	9	4	3	17
Benign	0	3	3	1	7
Conflicting	—				2
Total	2	199	8	4	215

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

38 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap YEATS2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →