H4C9

protein-coding

H4 clustered histone 9, the group of H4 histones

Gene summary

Histones are basic nuclear proteins that are responsible for the 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 H4 family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the histone microcluster on chromosome 6p21.33. [provided by RefSeq, Aug 2015]

Previous symbols:

H4FM
HIST1H4I

MANE transcript

NM_003495.3

Inheritance

ClinVar variants

P:2U:30B:3

Top phenotype

Tessadori-Bicknell-van Haaften neurodevelopmental syndrome 4

Max pathogenic AF

—

Genomic locus

chr6:27,139,282-27,140,640

External References & Databases

Ensembl (ENSG00000276180)

Transcript & Mutation Effects

hg38 • Region Span ~1.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

Tessadori-Van Haaften neurodevelopmental syndrome 4LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0031000

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Tessadori-Bicknell-van Haaften neurodevelopmental syndrome 4AD

Manifestation: Audiologic/Otolaryngologic; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal

Intervention: Genitourinary

Rationale: Among other features, the condition can involve genitourinary anomalies, including vesicoureteral reflux, and awareness may allow prompt diagnosis and management, which may help ameliorate renal sequelae

Refs: 35202563

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to H4C9 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 24

not providedTotal: 5

Tessadori-Van Haaften neurodevelopmental syndrome 4Total: 5

Craniosynostosis 7Total: 1

H4C9-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003495.3. 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 clinvar	2
missense	2 clinvar		30 clinvar	1 clinvar		33
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	2	0	30	2	1	35

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003495.3	RefSeq	NP_003486.1	1	MANE Select
ENST00000615353.2	Ensembl	ENSP00000481486.1	1	MANE Select
ENST00000715894.1	Ensembl	ENSP00000520530.1	1	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)
HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
B-WICH complex positively regulates rRNA expression

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.;
Disease: DISEASE: Note=Chromosomal aberrations involving HISTONE H4 is a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;6)(q27;p21), with BCL6. {ECO:0000269|PubMed:12414651}.;

Intolerance Scores

LoFtool: 0.439
RVIS EVS: -0.1
RVIS percentile EVS: 46.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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