H1-10

Chr 3

H1.10 linker histone

Also known as: H1.10, H1FX, H1X

NCBI Gene: 8971 ENSG00000184897 UniProt: Q92522 OMIM: 602785

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 H1 family. [provided by RefSeq, Oct 2015]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.35

LOEUF

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.35LOEUF

pLI 0.088

Z-score 1.11

OE 0.44 (0.18–1.35)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.46Z-score

OE missense 0.88 (0.75–1.04)

101 obs / 114.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.18–1.35)

0≤0.351.4

Missense OE?0.88 (0.75–1.04)

0≤0.61.4

Synonymous OE?1.23

0≤1.21.6

LoF obs/exp: 2 / 4.5Missense obs/exp: 101 / 114.8Syn Z: -1.29

Background carrier burden — how many people carry a rare variant somewhere in H1-10?

gnomAD v4 · ~727k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

327 rare PASS variants

Rare truncating (LoF)

1 in 9,000

24 rare PASS variants

Rare synonymous (reference)

1 in 160

202 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for H1-10. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~554k	1 in 220	1 in 14,000
South Asian	~42k	1 in 240	1 in 3,400
Remaining (unassigned)	~30k	1 in 170	none seen
European (Finnish)	~26k	1 in 430	≈ 1 in 6,900
Admixed American	~22k	1 in 260	≈ 1 in 8,800
African / African American	~21k	1 in 460	≈ 1 in 10,000
East Asian	~20k	1 in 270	≈ 1 in 5,700
Ashkenazi Jewish	~13k	1 in 2,400	none seen
Middle Eastern	~2,883	1 in 440	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 ↓