H1-5

Chr 6

H1.5 linker histone, cluster member

Also known as: H1, H1.5, H1B, H1F5, H1s-3, HIST1H1B

NCBI Gene: 3009ENSG00000184357UniProt: P16401

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 small histone gene cluster on chromosome 6p22-p21.3. [provided by RefSeq, Aug 2015]

65
ClinVar variants
4
Pathogenic / LP
0.57
pLI score
4
Active trials
Clinical Summary— H1-5
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.57) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
4 Pathogenic / Likely Pathogenic· 60 VUS of 65 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

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.
1.10LOEUF
pLI 0.575
Z-score 1.50
OE 0.00 (0.00–1.10)
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.
-3.54Z-score
OE missense 1.90 (1.69–1.98)
232 obs / 122.0 exp
Tolerant

Tolerant to missense variation

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 (0.00–1.10)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.90 (1.69–1.98)
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.2.25
0≤1.21.6
LoF obs/exp: 0 / 2.6Missense obs/exp: 232 / 122.0Syn Z: -7.13

ClinVar Variant Classifications

65 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
VUS60
Likely Benign1
4
Pathogenic
60
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
0
0
0
VUS
0
57
3
0
60
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total0578065

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

View in ClinVar →

Protein Context — Lollipop Plot

H1-5 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Histone H1 loss drives lymphoma by disrupting 3D chromatin architecture.
Yusufova N et al.·Nature
2021
Nuclear and nucleolar activity of linker histone variant H1.0.
Kowalski A·Cell Mol Biol Lett
2016Review
Linker histone H1.5 contributes to centromere integrity.
Saha A et al.·Nucleic Acids Res
2026
Site-specific regulation of histone H1 phosphorylation in pluripotent cell differentiation.
Liao R et al.·Epigenetics Chromatin
2017
Histone H1 variants are differentially expressed and incorporated into chromatin during differentiation and reprogramming to pluripotency.
Terme JM et al.·J Biol Chem
2011
Proteasome-dependent degradation of histone H1 subtypes is mediated by its C-terminal domain.
García-Gomis D et al.·Protein Sci
2024
Imaging analysis of six human histone H1 variants reveals universal enrichment of H1.2, H1.3, and H1.5 at the nuclear periphery and nucleolar H1X presence.
Salinas-Pena M et al.·Elife
2024
Native and tagged CENP-A histones are functionally inequivalent.
Bui M et al.·Epigenetics Chromatin
2024Functional
Promyelocytic leukemia zinc finger and histone H1.5 differentially stain low- and high-grade pulmonary neuroendocrine tumors: a pilot immunohistochemical study.
Hechtman JF et al.·Hum Pathol
2013
Functional analysis of tumor-derived immunoglobulin lambda and its interacting proteins in cervical cancer.
Wang J et al.·BMC Cancer
2023Functional
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
Acute Coronary SyndromeNursing

Acute Coronary Syndrome and Acupressure

RECRUITING
NCT06300294Phase NAAbant Izzet Baysal UniversityStarted 2024-10-01
acupressure
Aromatherapy

EFFECTS OF CİTRUS AND CLOVE OİL AROMATHERAPY İN OLDER ADULTS

NOT YET RECRUITING
NCT07368374Phase NAMersin UniversityStarted 2026-02-01
Intervention Group 1Intervention Group 2Placebo Control Group
Cerebral Palsy (CP)SpasticityMotor Learning

Predictors of Motor İmagery Performance in Cerebral Palsy

NOT YET RECRUITING
NCT07002567Abant Izzet Baysal UniversityStarted 2025-07-04
Implicit motor imageryExplicit motor imagery
Ventricular Arrhythmias

Evaluation of Electrocardiographic Measurements by High Density Electrode ECG

RECRUITING
NCT04921501Phase NAUniversity Hospital, BordeauxStarted 2021-04-06
HD ECGConventional 12-lead ECG

External Resources

Links to major genomics databases and tools