MEAF6

Chr 1

MYST/Esa1 associated factor 6

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

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.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.65
Clinical SummaryMEAF6
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
5 unique Pathogenic / Likely Pathogenic· 19 VUS of 42 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.65LOEUF
pLI 0.128
Z-score 2.49
OE 0.28 (0.140.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.23Z-score
OE missense 0.40 (0.310.52)
44 obs / 109.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.28 (0.140.65)
00.351.4
Missense OE0.40 (0.310.52)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 4 / 14.1Missense obs/exp: 44 / 109.9Syn Z: 0.38
DN
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

42 submitted variants in ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS19
Likely Benign1
4
Pathogenic
1
Likely Pathogenic
19
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
1
0
1
VUS
0
16
3
0
19
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total0169025

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

View in ClinVar →

Protein Context — Lollipop Plot

MEAF6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC