H2AX

Chr 11

H2A.X variant histone

Also known as: H2A.X, H2A/X, H2AFX

NCBI Gene: 3014 ENSG00000188486 UniProt: P16104 OMIM: 601772

Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene encodes a replication-independent histone that is a member of the histone H2A family, and generates two transcripts through the use of the conserved stem-loop termination motif, and the polyA addition motif. [provided by RefSeq, Oct 2015]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Active trials

748

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.63

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — H2AX

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.63LOEUF

pLI 0.177

Z-score 0.86

OE 0.41 (0.14–1.63)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

2.03Z-score

OE missense 0.38 (0.28–0.51)

32 obs / 84.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.41 (0.14–1.63)

0≤0.351.4

Missense OE?0.38 (0.28–0.51)

0≤0.61.4

Synonymous OE?1.33

0≤1.21.6

LoF obs/exp: 1 / 2.4Missense obs/exp: 32 / 84.7Syn Z: -1.74

Background carrier burden — how many people carry a rare variant somewhere in H2AX?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 1,800

116 rare PASS variants

Rare truncating (LoF)

1 in 19,000

10 rare PASS variants

Rare synonymous (reference)

1 in 540

116 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for H2AX. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 8 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 1,900	1 in 69,000
South Asian	~43k	1 in 880	1 in 2,400
Remaining (unassigned)	~30k	1 in 1,900	none seen
European (Finnish)	~27k	≈ 1 in 8,800	≈ 1 in 24,000
Admixed American	~22k	1 in 2,100	none seen
African / African American	~21k	1 in 1,600	≈ 1 in 10,000
East Asian	~20k	1 in 1,900	none seen
Middle Eastern	~2,884	≈ 1 in 2,900	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓