H4C7

Summary

H4C7 (H4 clustered histone 7, HGNC:4792) is a protein-coding gene on chromosome 6p22.2, encoding Histone H4-like protein type G (Q99525). Core component of nucleosome.

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 large histone gene cluster on chromosome 6.

Source: NCBI Gene 8369 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_003547

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4792
Approved symbol	H4C7
Name	H4 clustered histone 7
Location	6p22.2
Locus type	gene with protein product
Status	Approved
Aliases	H4/l
Ensembl gene	ENSG00000275663
Ensembl biotype	protein_coding
OMIM	602832
Entrez	8369

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000611444

RefSeq mRNA: 1 — MANE Select: NM_003547 NM_003547

CCDS: CCDS4599

Canonical transcript exons

ENST00000611444 — 1 exons

Exon	Start	End
ENSE00003754862	26246611	26246996

Expression profiles

Bgee: expression breadth broad, 11 present calls, max score 59.37.

Top tissues by expression

254 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	59.37	silver quality
decidua	UBERON:0002450	56.55	gold quality
cranial nerve II	UBERON:0000941	55.99	gold quality
ileal mucosa	UBERON:0000331	54.26	silver quality
deltoid	UBERON:0001476	53.34	silver quality
hair follicle	UBERON:0002073	52.43	gold quality
triceps brachii	UBERON:0001509	52.21	gold quality
quadriceps femoris	UBERON:0001377	49.37	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
tendon of biceps brachii	UBERON:0008188	49.11	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
epithelial cell of pancreas	CL:0000083	48.78	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
oviduct epithelium	UBERON:0004804	48.00	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
nasal cavity epithelium	UBERON:0005384	47.70	gold quality
thymus	UBERON:0002370	47.42	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.81

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• A novel histone H4 variant H4G regulates ribosomal DNA transcription in breast cancer. (PMID:31219579)

Cross-species orthologs

19 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	His4:CG33875	FBGN0053875
drosophila_melanogaster	His4:CG33889	FBGN0053889
drosophila_melanogaster	His4:CG33903	FBGN0053903
caenorhabditis_elegans		WBGENE00001875
caenorhabditis_elegans		WBGENE00001879
caenorhabditis_elegans		WBGENE00001884
caenorhabditis_elegans		WBGENE00001888
caenorhabditis_elegans		WBGENE00001892
caenorhabditis_elegans		WBGENE00001900
caenorhabditis_elegans		WBGENE00001902
caenorhabditis_elegans		WBGENE00001905
caenorhabditis_elegans		WBGENE00001911
caenorhabditis_elegans		WBGENE00001912
caenorhabditis_elegans		WBGENE00001920
caenorhabditis_elegans		WBGENE00001924
caenorhabditis_elegans		WBGENE00001930
caenorhabditis_elegans		WBGENE00001934
caenorhabditis_elegans		WBGENE00001938
caenorhabditis_elegans	his-67	WBGENE00001941

Paralogs (14): H4C8 (ENSG00000158406), H4C3 (ENSG00000197061), H4C11 (ENSG00000197238), H4C16 (ENSG00000197837), H4C15 (ENSG00000270276), H4C14 (ENSG00000270882), H4C12 (ENSG00000273542), H4C6 (ENSG00000274618), H4C13 (ENSG00000275126), H4C9 (ENSG00000276180), H4C5 (ENSG00000276966), H4C4 (ENSG00000277157), H4C1 (ENSG00000278637), H4C2 (ENSG00000278705)

Protein

Protein identifiers

Histone H4-like protein type G — Q99525 (reviewed: Q99525)

Alternative names: H4-clustered histone 7

All UniProt accessions (1): Q99525

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.

Subcellular location. Nucleus. Chromosome.

Similarity. Belongs to the histone H4 family.

RefSeq proteins (1): NP_003538* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001951	Histone_H4	Family
IPR009072	Histone-fold	Homologous_superfamily

UniProt features (2 total): chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99525-F1	87.89	0.72

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 27 (showing top): GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, GOBP_CHROMATIN_REMODELING, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, GOCC_PROTEIN_DNA_COMPLEX, IRF2_01, GOMF_PROTEIN_HETERODIMERIZATION_ACTIVITY, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, GOBP_NUCLEOSOME_ORGANIZATION, IRF1_01, WP_HISTONE_MODIFICATIONS, GAL_LEUKEMIC_STEM_CELL_DN, GOCC_NUCLEOSOME, GOMF_STRUCTURAL_CONSTITUENT_OF_CHROMATIN, GSE2706_LPS_VS_R848_AND_LPS_8H_STIM_DC_DN

GO Biological Process (1): nucleosome assembly (GO:0006334)

GO Molecular Function (4): DNA binding (GO:0003677), structural constituent of chromatin (GO:0030527), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (3): nucleosome (GO:0000786), nucleus (GO:0005634), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin	2
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
nucleic acid binding	1
structural molecule activity	1
protein dimerization activity	1
binding	1
protein-DNA complex	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

3096 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H4C7	H2AC20	Q16777	999
H4C7	H2AC19	P20670	999
H4C7	H3-3A	P06351	998
H4C7	H3C14	Q71DI3	998
H4C7	H3-4	Q16695	998
H4C7	H3-5	Q6NXT2	997
H4C7	H3C1	P02295	997
H4C7	H2BC21	Q16778	997
H4C7	H3-7	Q5TEC6	997
H4C7	BRD4	O60885	993
H4C7	BRDT	Q58F21	986
H4C7	RBBP4	P31149	985
H4C7	TP53BP1	Q12888	979
H4C7	BRD2	P25440	979
H4C7	HJURP	Q8NCD3	973

IntAct

29 interactions, top by confidence:

A	B	Type	Score
AGTRAP	H4C7	psi-mi:“MI:0915”(physical association)	0.560
H4C7	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560
H4C7	FKBP7	psi-mi:“MI:0915”(physical association)	0.560
MAIP1	H4C7	psi-mi:“MI:0915”(physical association)	0.560
TMED8	H4C7	psi-mi:“MI:0915”(physical association)	0.560
FGF14	H4C7	psi-mi:“MI:0915”(physical association)	0.560
H4C7	CIDEB	psi-mi:“MI:0915”(physical association)	0.560
RHBDD2	H4C7	psi-mi:“MI:0915”(physical association)	0.560
APOC1	H4C7	psi-mi:“MI:0915”(physical association)	0.560
H4C7	H1-4	psi-mi:“MI:0915”(physical association)	0.400
H4C7	H3C13	psi-mi:“MI:0915”(physical association)	0.400
HMGN1	H2AX	psi-mi:“MI:0914”(association)	0.350
HMGN1	IPO7	psi-mi:“MI:0914”(association)	0.350
TMED8	H4C7	psi-mi:“MI:0915”(physical association)	0.000
MAIP1	H4C7	psi-mi:“MI:0915”(physical association)	0.000
H4C7	FGF14	psi-mi:“MI:0915”(physical association)	0.000
H4C7	CIDEB	psi-mi:“MI:0915”(physical association)	0.000
H4C7	RHBDD2	psi-mi:“MI:0915”(physical association)	0.000
H4C7	APOC1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (41): AGTRAP (Two-hybrid), HIST1H4G (Affinity Capture-MS), HIST1H4G (Two-hybrid), HIST1H4G (Two-hybrid), HIST1H4G (Two-hybrid), HIST1H4G (Two-hybrid), HIST1H4G (Two-hybrid), HIST1H4G (Two-hybrid), HIST1H4G (Two-hybrid), HIST1H4G (Proximity Label-MS), HIST1H4G (Proximity Label-MS), HIST1H4G (Affinity Capture-MS), HIST1H4G (Affinity Capture-MS), HIST1H4G (Affinity Capture-MS), HIST1H4G (Affinity Capture-MS)

ESM2 similar proteins: A0A097I1R9, A0A097I2D0, P02309, P02310, P04915, P08436, P09322, P23750, P23751, P35057, P35059, P40287, P50566, P62786, P62790, P62791, P62792, P62793, P69151, P69152, P70081, P81202, P91849, P91890, Q27443, Q27490, Q41811, Q54BC2, Q54LA5, Q54Z07, Q5M8Q2, Q6LAF1, Q6V9I2, Q6ZXX3, Q71V09, Q757K0, Q75AX1, Q76MU7, Q76NW2, Q8J1L3

Diamond homologs: P02309, P04914, P04915, P08436, P09322, P0CG89, P23750, P23751, P27996, P35057, P35059, P50566, P59259, P62776, P62777, P62778, P62779, P62780, P62781, P62782, P62783, P62784, P62785, P62786, P62787, P62788, P62789, P62792, P62793, P62794, P62795, P62796, P62797, P62798, P62799, P62800, P62801, P62802, P62803, P62804

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

29 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

48 predictions. Top by Δscore:

Variant	Effect	Δscore
6:26246694:C:A	donor_gain	0.8600
6:26246693:T:TA	donor_gain	0.6500
6:26246820:TC:T	acceptor_gain	0.6500
6:26246683:A:AC	donor_gain	0.5800
6:26246684:C:CC	donor_gain	0.5800
6:26246685:A:C	donor_gain	0.5200
6:26246774:CCAGA:C	donor_gain	0.4700
6:26246851:CGCCA:C	acceptor_gain	0.4500
6:26246817:TCCTC:T	acceptor_gain	0.4400
6:26246929:TGGC:T	donor_gain	0.4400
6:26246712:TAG:T	donor_gain	0.4100
6:26246713:AGA:A	donor_gain	0.4100
6:26246821:C:CT	acceptor_gain	0.4100
6:26246799:T:TG	acceptor_gain	0.3900
6:26246908:TCAG:T	donor_gain	0.3700
6:26246821:C:A	acceptor_gain	0.3600
6:26246909:CAGTA:C	donor_loss	0.3600
6:26246910:AGTAC:A	donor_loss	0.3600
6:26246911:GTA:G	donor_loss	0.3600
6:26246912:TA:T	donor_loss	0.3600
6:26246913:A:AT	donor_loss	0.3600
6:26246914:CCTT:C	donor_loss	0.3600
6:26246915:C:A	donor_loss	0.3500
6:26246822:A:C	acceptor_gain	0.3300
6:26246928:TTGG:T	donor_gain	0.3300
6:26246684:CAGGG:C	donor_gain	0.3100
6:26246771:G:T	donor_gain	0.3100
6:26246800:TGAAC:T	donor_gain	0.3100
6:26246818:CCTCA:C	acceptor_gain	0.3100
6:26246800:T:A	acceptor_gain	0.2900

AlphaMissense

622 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:26246792:G:C	F62L	0.750
6:26246792:G:T	F62L	0.750
6:26246794:A:G	F62L	0.750

dbSNP variants (sampled 300 via entrez): RS1002316739 (6:26246276 G>A,T), RS1003351870 (6:26248016 G>C), RS1003486567 (6:26248303 A>G), RS1004131048 (6:26247994 G>A), RS1005159557 (6:26246301 A>G), RS1005368475 (6:26247134 A>G), RS1005834083 (6:26247394 C>A), RS1006785323 (6:26248346 G>T), RS1007821828 (6:26247041 AC>A), RS1011276476 (6:26246298 A>G), RS1011355118 (6:26246709 A>C), RS1013445555 (6:26248074 C>A), RS1015391874 (6:26247410 C>A,T), RS1015429380 (6:26247700 C>G), RS1015453772 (6:26247489 T>C,G)

Disease associations

OMIM: gene MIM:602832 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST004521_113	Autism spectrum disorder or schizophrenia	3.000000e-19
GCST004521_142	Autism spectrum disorder or schizophrenia	2.000000e-09
GCST004521_169	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_69	Autism spectrum disorder or schizophrenia	8.000000e-24
GCST004521_83	Autism spectrum disorder or schizophrenia	1.000000e-13
GCST004571_19	Iron status biomarkers (total iron binding capacity)	2.000000e-08
GCST004572_27	Iron status biomarkers (transferrin saturation)	2.000000e-08
GCST007294_143	Body fat distribution (trunk fat ratio)	5.000000e-29
GCST007294_82	Body fat distribution (trunk fat ratio)	1.000000e-48
GCST007295_120	Body fat distribution (leg fat ratio)	2.000000e-46
GCST007295_91	Body fat distribution (leg fat ratio)	1.000000e-26
GCST010002_50	Refractive error	4.000000e-34
GCST010083_312	Hemoglobin levels	6.000000e-44
GCST010141_1	Beef consumption	7.000000e-13
GCST010143_19	Meat-related diet	5.000000e-13
GCST010143_31	Meat-related diet	7.000000e-09
GCST010143_5	Meat-related diet	4.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006334	total iron binding capacity
EFO:0004341	body fat distribution
EFO:0004509	hemoglobin measurement
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Aldehydes	decreases expression	1
Arsenic	affects methylation	1
Citrulline	decreases expression	1
Coal	increases abundance, increases expression	1
Diethylhexyl Phthalate	increases expression	1
Lead	increases expression	1
Smoke	increases abundance, increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.