H1-4

Chr 6AD

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]

Primary Disease Associations & Inheritance

Rahman syndromeMIM #617537
AD
255
ClinVar variants
42
Pathogenic / LP
0.19
pLI score
6
Active trials
Clinical Summary— H1-4
🧬
Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.19) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
42 Pathogenic / Likely Pathogenic· 115 VUS of 255 total submissions
💊
Clinical Trials
6 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.
1.59LOEUF
pLI 0.186
Z-score 0.91
OE 0.39 (0.13–1.59)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?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.
-6.72Z-score
OE missense 2.68 (1.94–2.00)
340 obs / 127.0 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.0.39 (0.13–1.59)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.2.68 (1.94–2.00)
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.3.83
0≤1.21.6
LoF obs/exp: 1 / 2.6Missense obs/exp: 340 / 127.0Syn Z: -16.76

ClinVar Variant Classifications

255 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic14
VUS115
Likely Benign92
Benign3
Conflicting3
28
Pathogenic
14
Likely Pathogenic
115
VUS
92
Likely Benign
3
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
22
0
6
0
28
Likely Pathogenic
11
2
1
0
14
VUS
13
85
17
0
115
Likely Benign
0
54
2
36
92
Benign
0
0
0
3
3
Conflicting
—3
Total461412639255

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

View in 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.

Gene2Phenotype Curations

H1-4-related Rahman syndrome

strong
ADLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Rahman syndrome

MIM #617537

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — H1-4
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
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
CYP1B1 promotes PARPi-resistance via histone H1.4 interaction and increased chromatin accessibility in ovarian cancer.
Xue Y et al.·Drug Resist Updat
2024
Mutations in Epigenetic Regulation Genes Are a Major Cause of Overgrowth with Intellectual Disability.
Tatton-Brown K et al.·Am J Hum Genet
2017
Ubiquitin-conjugating enzyme E2C: a potential cancer biomarker.
Xie C et al.·Int J Biochem Cell Biol
2014Review
Dynamics and dispensability of variant-specific histone H1 Lys-26/Ser-27 and Thr-165 post-translational modifications.
Terme JM et al.·FEBS Lett
2014
Coordinated changes in gene expression, H1 variant distribution and genome 3D conformation in response to H1 depletion.
Serna-Pujol N et al.·Nucleic Acids Res
2022
Antimicrobial and antibiofilm activity of human recombinant H1 histones against bacterial infections.
Arévalo-Jaimes BV et al.·mSystems
2024
Proteomic analysis of tears in dry eye disease: A prospective, double-blind multicenter study.
Jung GT et al.·Ocul Surf
2023
Site-specific regulation of histone H1 phosphorylation in pluripotent cell differentiation.
Liao R et al.·Epigenetics Chromatin
2017
Site-Specific Phosphorylation of Histone H1.4 Is Associated with Transcription Activation.
Saha A et al.·Int J Mol Sci
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
RetreatmentAsymptomatic Apical Periodontitis

Effects of Irrigation Activation Systems on Postoperative Pain and Lesion Healing in Single-Visit Retreatment

ACTIVE NOT RECRUITING
NCT07150585Phase NAEge UniversityStarted 2024-08-01
Ultrasonic Activation GroupSonic Activation GroupLaser Activation 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
HypersensitivityHypersensitivity, ImmediateHypersensitivity Response

Assessment of Er:YAG Laser for the Control of Hypersensitivity During Tooth Whitening With Hydrogen Peroxide

NOT YET RECRUITING
NCT06538129Phase NAUniversity of Nove de JulhoStarted 2024-11-01
Hypersensitivity prevention protocol with Er:YAG laserHypersensitivity prevention protocol with neutral sodium fluoride gel

External Resources

Links to major genomics databases and tools