H2AZ2

Chr 7

H2A.Z variant histone 2

Also known as: H2A.Z-2, H2AFV, H2AV

NCBI Gene: 94239ENSG00000105968UniProt: Q71UI9

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. Several transcript variants encoding different isoforms, have been identified for this gene. [provided by RefSeq, Oct 2015]

30
ClinVar variants
24
Pathogenic / LP
0.47
pLI score
0
Active trials
Clinical Summary— H2AZ2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.17) despite low pLI — interpret in context.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 5 VUS of 30 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.82LOEUF
pLI 0.471
Z-score 1.84
OE 0.17 (0.06–0.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.24Z-score
OE missense 0.28 (0.20–0.41)
22 obs / 77.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.17 (0.06–0.82)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.28 (0.20–0.41)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.72
0≤1.21.6
LoF obs/exp: 1 / 5.8Missense obs/exp: 22 / 77.3Syn Z: 1.15

ClinVar Variant Classifications

30 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic1
VUS5
Likely Benign1
23
Pathogenic
1
Likely Pathogenic
5
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————23
Likely Pathogenic
————1
VUS
————5
Likely Benign
————1
Benign
————0
Total—30

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

H2AZ2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

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