H1-1

protein-coding

H1.1 linker histone, cluster member, the group of H1 histones

Gene summary

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]

Previous symbols:

H1F1
HIST1H1A

MANE transcript

NM_005325.4

Inheritance

—

ClinVar variants

U:72B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 2.72

Max pathogenic AF

—

Genomic locus

chr6:26,017,032-26,017,787

External References & Databases

Ensembl (ENSG00000124610)

Transcript & Mutation Effects

hg38 • Region Span ~0.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to H1-1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 79

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005325.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense			72 clinvar	7 clinvar		79
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	72	9	0	81

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005325.4	RefSeq	NP_005316.1	1	MANE Select
ENST00000244573.5	Ensembl	ENSP00000244573.4	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Formation of Senescence-Associated Heterochromatin Foci (SAHF)
DNA Damage/Telomere Stress Induced Senescence
Cellular Senescence
Cellular responses to stress
Activation of DNA fragmentation factor

Biological Process

nucleosome assembly
regulation of transcription, DNA-templated
spermatogenesis
nucleosome positioning
chromosome condensation

Molecular Function

double-stranded DNA binding
protein binding
heparin binding
chromatin DNA binding
nucleosomal DNA binding

Cellular Component

nucleosome
nuclear chromatin
nucleus
nuclear euchromatin
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000244573
Coding exons: 1
Length: 781
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-3.99	249	124	2.01	0.00000720	1354
Missense (PolyPhen)		54	33.837	1.5959		359
Synonymous	-6.87	121	55.7	2.17	0.00000393	475
Loss of Function	-2.74	8	2.94	2.72	1.24e-7	66

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Acts also as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.213

Intolerance Scores

LoFtool: 0.893
RVIS EVS: -0.09
RVIS percentile EVS: 47.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.977

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium