H1-8

Chr 3

H1.8 linker histone

Also known as: H1.8, H1FOO, H1oo, osH1

NCBI Gene: 132243 ENSG00000178804 UniProt: Q8IZA3 OMIM: 142712

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. The protein encoded is a replication-independent histone that is a member of the histone H1 family. This gene contains introns, unlike most histone genes. The related mouse gene is expressed only in oocytes. [provided by RefSeq, Oct 2015]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.97

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.97LOEUF

pLI 0.070

Z-score 1.64

OE 0.37 (0.17–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.37Z-score

OE missense 0.93 (0.82–1.05)

191 obs / 205.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.37 (0.17–0.97)

0≤0.351.4

Missense OE?0.93 (0.82–1.05)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 3 / 8.0Missense obs/exp: 191 / 205.8Syn Z: -0.59

Background carrier burden — how many people carry a rare variant somewhere in H1-8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

456 rare PASS variants

Rare truncating (LoF)

1 in 2,700

68 rare PASS variants

Rare synonymous (reference)

1 in 180

200 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for H1-8. 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)	~556k	1 in 130	1 in 2,800
South Asian	~43k	1 in 96	1 in 6,900
Remaining (unassigned)	~30k	1 in 120	1 in 2,800
European (Finnish)	~27k	1 in 1,100	1 in 4,200
Admixed American	~22k	1 in 120	1 in 1,000
African / African American	~21k	1 in 110	1 in 1,300
East Asian	~20k	1 in 110	≈ 1 in 6,200
Ashkenazi Jewish	~13k	1 in 570	1 in 1,900
Middle Eastern	~2,884	1 in 120	≈ 1 in 780

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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓