MACROH2A2

Chr 10

macroH2A.2 histone

Also known as: H2AFY2

NCBI Gene: 55506ENSG00000099284UniProt: Q9P0M6

Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene encodes a replication-independent histone that is a member of the histone H2A family. It replaces conventional H2A histones in a subset of nucleosomes where it represses transcription and may participate in stable X chromosome inactivation. [provided by RefSeq, Oct 2015]

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.
0
Active trials
3
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.30
LOEUF· LoF intol.
—
Mechanism
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.30LOEUF
pLI 0.976
Z-score 3.46
OE 0.06 (0.02–0.30)
Highly constrained

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

Missense Constraint?
2.92Z-score
OE missense 0.47 (0.40–0.55)
110 obs / 236.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.06 (0.02–0.30)
0≤0.351.4
Missense OE?0.47 (0.40–0.55)
0≤0.61.4
Synonymous OE?0.93
0≤1.21.6
LoF obs/exp: 1 / 15.9Missense obs/exp: 110 / 236.2Syn Z: 0.56

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

MACROH2A2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients