H1-3

Chr 6

H1.3 linker histone, cluster member

Also known as: H1.3, H1D, H1F3, H1s-2, HIST1H1D

NCBI Gene: 3007ENSG00000124575UniProt: P16402

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]

131
ClinVar variants
4
Pathogenic / LP
0.16
pLI score
7
Active trials
Clinical Summary— H1-3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.16) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
4 Pathogenic / Likely Pathogenic· 116 VUS of 131 total submissions
💊
Clinical Trials
7 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.71LOEUF
pLI 0.156
Z-score 0.73
OE 0.47 (0.16–1.71)
Tolerant

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.
-8.06Z-score
OE missense 3.07 (1.95–2.00)
368 obs / 119.7 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.0.47 (0.16–1.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.3.07 (1.95–2.00)
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.3.23
0≤1.21.6
LoF obs/exp: 1 / 2.1Missense obs/exp: 368 / 119.7Syn Z: -12.33

ClinVar Variant Classifications

131 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
VUS116
Likely Benign11
4
Pathogenic
116
VUS
11
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
107
9
0
116
Likely Benign
0
8
2
1
11
Benign
0
0
0
0
0
Total0115151131

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

View in ClinVar →

Protein Context — Lollipop Plot

H1-3 · 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
Histone profiling reveals the H1.3 histone variant as a prognostic biomarker for pancreatic ductal adenocarcinoma.
Bauden M et al.·BMC Cancer
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
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
Variant SNPs at the microRNA complementary site in the B7‑H1 3'‑untranslated region increase the risk of non‑small cell lung cancer.
Du W et al.·Mol Med Rep
2017
Huwe1 Sustains Normal Ovarian Epithelial Cell Transformation and Tumor Growth through the Histone H1.3-H19 Cascade.
Yang D et al.·Cancer Res
2017
Inhibition of gamma-thrombin-induced human platelet aggregation by histone H1subtypes and H1.3 fragments.
Soslau G et al.·Platelets
2009
MicroRNA-152 regulates immune response via targeting B7-H1 in gastric carcinoma.
Wang Y et al.·Oncotarget
2017
Quantitative Mass Spectrometry Reveals that Intact Histone H1 Phosphorylations are Variant Specific and Exhibit Single Molecule Hierarchical Dependence.
Chen Y et al.·Mol Cell Proteomics
2016
Genomic analysis of fluoroquinolone-susceptible phylogenetic group B2 extraintestinal pathogenic Escherichia coli causing infections in cats.
Kidsley AK et al.·Vet Microbiol
2020
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
PainSatisfaction

Effects of Shotblocker and Manual Pressure on Pain and Satisfaction

NOT YET RECRUITING
NCT06947525Phase NANecmettin Erbakan UniversityStarted 2025-04-28
Manual pressureShotblocker
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
Infertility

The Enchanting Symphony of Haptonomy's Impact on Attachment and Spousal Harmony for Women Conceiving Through Infertility Treatment

ENROLLING BY INVITATION
NCT06274138Phase NABaskent UniversityStarted 2024-09-15
haptonomy
Risky BabyMotor DevelopmentSensory Profiles

Are Developmentally At Risky Babies Environmentally Disadvantaged?

NOT YET RECRUITING
NCT07063966Abant Izzet Baysal UniversityStarted 2025-07-03
Motivational InterviewingHealth Care Seeking BehaviorMigrants

The Effect of Motivational Interviewing-Based Health Behavior Training in Chronically Ill Migrant Women

NOT YET RECRUITING
NCT06505707Phase NAKahramanmaraş İstiklal UniversityStarted 2024-07-15
Health Seeking Behavior Training Based on Motivational Interviewing Techniques

External Resources

Links to major genomics databases and tools