H2AC6

Chr 6

H2A clustered histone 6

Also known as: H2A/l, H2AFL, HIST1H2AC, dJ221C16.4

NCBI Gene: 8334ENSG00000180573UniProt: Q93077

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 is intronless and encodes a replication-dependent histone that is a member of the histone H2A family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6. [provided by RefSeq, Aug 2015]

31
ClinVar variants
6
Pathogenic / LP
0.60
pLI score
0
Active trials
Clinical Summary— H2AC6
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.60) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 23 VUS of 31 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
1.03LOEUF
pLI 0.596
Z-score 1.56
OE 0.00 (0.00–1.03)
Moderately constrained

Highly tolerant — LoF variants common in population

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.
0.53Z-score
OE missense 0.83 (0.68–1.02)
66 obs / 79.4 exp
Tolerant

Mild missense constraint

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.0.00 (0.00–1.03)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.68–1.02)
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.2.56
0≤1.21.6
LoF obs/exp: 0 / 2.8Missense obs/exp: 66 / 79.4Syn Z: -7.32

ClinVar Variant Classifications

31 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic1
VUS23
Likely Benign1
Benign1
5
Pathogenic
1
Likely Pathogenic
23
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
1
0
1
VUS
0
12
11
0
23
Likely Benign
0
0
1
0
1
Benign
1
0
0
0
1
Total11218031

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

View in ClinVar →

Protein Context — Lollipop Plot

H2AC6 · protein map & ClinVar variants

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

Gene2Phenotype Curations

H2AC6-related developmental disorder

limited
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

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
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