H2AC21

Chr 1

H2A clustered histone 21

Also known as: H2AB, HIST2H2AB

NCBI Gene: 317772 ENSG00000184270 UniProt: Q8IUE6 OMIM: 615014

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 is intronless and encodes a replication-dependent histone that is a member of the histone H2A family. Transcripts from this gene contain a palindromic termination element. [provided by RefSeq, Aug 2015]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.98

Clinical Summary— H2AC21

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.61) — some intolerance to loss-of-function variants.

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ClinVar Variants

19 VUS of 25 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.98LOEUF

pLI 0.615

Z-score 1.61

OE 0.00 (0.00–0.98)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

0.87Z-score

OE missense 0.73 (0.59–0.91)

59 obs / 80.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.98)

0≤0.351.4

Missense OE?0.73 (0.59–0.91)

0≤0.61.4

Synonymous OE?1.57

0≤1.21.6

LoF obs/exp: 0 / 3.0Missense obs/exp: 59 / 80.9Syn Z: -2.74

This gene — mechanism propensity

0.82top 10%

GOF

0.4184th %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

25 submitted variants in ClinVar

ClinVar

Classification Summary

VUS19

Likely Benign6

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	19	0	19
Likely Benign	0	6	6
Benign	0	0	0
Total	19	6	25

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

View in ClinVar →

12 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap H2AC21 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →