H1-4

Chr 6

H1.4 linker histone, cluster member

Also known as: H1.4, H1E, H1F4, H1s-4, HIST1H1E, RMNS, dJ221C16.5

NCBI Gene: 3008ENSG00000168298UniProt: P10412

Histones are basic nuclear proteins responsible for 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 H1 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]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtRahman syndrome

Clinical highlights

Gene-disease validity (ClinGen)
syndromic intellectual disability · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
5
Active trials
6
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
1.59
LOEUF
LOF
Mechanism· G2P
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GeneReview available — H1-4
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
1.59LOEUF
pLI 0.186
Z-score 0.91
OE 0.39 (0.13–1.59)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-6.72Z-score
OE missense 2.68 (1.94–2.00)
340 obs / 127.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.39 (0.13–1.59)
0≤0.351.4
Missense OE?2.68 (1.94–2.00)
0≤0.61.4
Synonymous OE?3.83
0≤1.21.6
LoF obs/exp: 1 / 2.6Missense obs/exp: 340 / 127.0Syn Z: -16.76

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

H1-4 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients