H2BC18

protein-coding

H2B clustered histone 18, the group of H2B histones

Gene summary

Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. This structure consists of approximately 146 bp of DNA wrapped around a nucleosome, an octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene encodes a replication-dependent histone that is a member of the histone H2B family and is found in a histone cluster on chromosome 1. [provided by RefSeq, Aug 2015]

Previous symbols:

HIST2H2BF

MANE transcript

NM_001024599.5

Inheritance

—

ClinVar variants

U:11B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.21

Max pathogenic AF

—

Genomic locus

chr1:149,782,689-149,812,373

External References & Databases

Ensembl (ENSG00000203814)

Transcript & Mutation Effects

hg38 • Region Span ~29.7 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 H2BC18 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 11

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001024599.5. 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				1 clinvar		1
missense			11 clinvar			11
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	11	1	0	12

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001024599.5	RefSeq	NP_001019770.1	1	MANE Select
ENST00000369167.3	Ensembl	ENSP00000358164.1	1	MANE Select
NM_001161334.2	RefSeq	NP_001154806.1	2	Standard
ENST00000545683.1	Ensembl	ENSP00000445831.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Systemic lupus erythematosus - Homo sapiens (human)
Viral carcinogenesis - Homo sapiens (human)
Alcoholism - Homo sapiens (human)
Post-translational protein modification
HDACs deacetylate histones

Biological Process

nucleosome assembly

Molecular Function

molecular_function
DNA binding
protein heterodimerization activity

Cellular Component

nucleosome
nucleus
nucleoplasm
cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000545683
Coding exons: 2
Length: 29684
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125747
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.693	62	79.4	0.781	0.00000459	856
Missense (PolyPhen)		16	26.704	0.59917		335
Synonymous	-5.21	75	35.5	2.11	0.00000227	275
Loss of Function	-0.303	3	2.49	1.21	1.06e-7	47

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.783
RVIS EVS: 0.17
RVIS percentile EVS: 65.33

Essentials

Essential (CRISPR): E
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.485

Gene Damage Prediction

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