H1-6

protein-coding

H1.6 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:

H1FT
HIST1H1T

MANE transcript

NM_005323.4

Inheritance

—

ClinVar variants

U:87B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e —

Max pathogenic AF

—

Genomic locus

chr6:26,107,412-26,108,135

External References & Databases

Ensembl (ENSG00000187475)

Transcript & Mutation Effects

hg38 • Region Span ~0.7 kb

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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 H1-6 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 96

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005323.4. 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						0
missense			87 clinvar	9 clinvar		96
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	87	9	0	96

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_005323.4	RefSeq	NP_005314.2	1	MANE Select
ENST00000338379.6	Ensembl	ENSP00000341214.5	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

nucleosome assembly
regulation of transcription, DNA-templated
multicellular organism development
spermatogenesis
binding of sperm to zona pellucida

Molecular Function

double-stranded DNA binding
protein binding
nucleosomal DNA binding

Cellular Component

nucleosome
condensed nuclear chromosome
nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000338379
Coding exons: 1
Length: 725

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-6.10	293	112	2.62	0.00000638	1311
Missense (PolyPhen)		72	33.79	2.1308		392
Synonymous	-9.08	128	48.0	2.67	0.00000324	444
Loss of Function

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: Testis-specific histone H1 that forms less compacted chromatin compared to other H1 histone subtypes (PubMed:26757249). Formation of more relaxed chromatin may be required to promote chromatin architecture required for proper chromosome regulation during meiosis, such as homologous recombination (PubMed:26757249). Histones H1 act as linkers that bind to nucleosomes and compact polynucleosomes into a higher-order chromatin configuration (Probable). {ECO:0000269|PubMed:26757249, ECO:0000305}.;

Recessive Scores

pRec: 0.162

Intolerance Scores

LoFtool: 0.826
RVIS EVS: 0.6
RVIS percentile EVS: 82.87

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.676

Gene Damage Prediction

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