MEAF6

Chr 1

MYST/Esa1 associated factor 6

Also known as: C1orf149, CENP-28, EAF6, NY-SAR-91

NCBI Gene: 64769 ENSG00000163875 UniProt: Q9HAF1 OMIM: 611001

The protein functions as a component of multiple histone acetyltransferase complexes (NuA4, HBO1, and MOZ/MORF) that regulate gene transcription by acetylating histones H2A, H3, and H4. Mutations in this gene cause autosomal recessive intellectual disability with seizures and hypotonia, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants, consistent with its role in fundamental transcriptional regulation processes.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a nuclear protein involved in transcriptional activation. The encoded protein may form a component of several different histone acetyltransferase complexes. There is a pseudogene for this gene on chromosome 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.65

Clinical Summary— MEAF6

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

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ClinVar Variants

16 VUS of 33 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.128

Z-score 2.49

OE 0.28 (0.14–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.23Z-score

OE missense 0.40 (0.31–0.52)

44 obs / 109.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.28 (0.14–0.65)

0≤0.351.4

Missense OE?0.40 (0.31–0.52)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 4 / 14.1Missense obs/exp: 44 / 109.9Syn Z: 0.38

This gene — mechanism propensity

0.75top 25%

GOF

0.3789th %ile

LOF

0.50top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

33 submitted variants in ClinVar

ClinVar

Classification Summary

VUS16

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	16	16
Likely Benign	0	0
Benign	0	0
Total	16	16

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

View in ClinVar →

5 pathogenic / likely-pathogenic (of 10) ClinVar copy-number / structural variants overlap MEAF6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →