H2AP

Summary

H2AP (H2A.P histone, HGNC:18417) is a protein-coding gene on chromosome Xp11.4, encoding Huntingtin-interacting protein M (O75409).

This gene encodes a protein shown to interact with huntingtin, which contains an expanded polyglutamine tract in individuals with Huntington’s disease (PMID: 9700202).

Source: NCBI Gene 25763 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 20 total — 1 pathogenic
• MANE Select transcript: NM_012274

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18417
Approved symbol	H2AP
Name	H2A.P histone
Location	Xp11.4
Locus type	gene with protein product
Status	Approved
Aliases	HIP17
Ensembl gene	ENSG00000187516
Ensembl biotype	protein_coding
Entrez	25763

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000341016

RefSeq mRNA: 1 — MANE Select: NM_012274 NM_012274

CCDS: CCDS43929

Canonical transcript exons

ENST00000341016 — 1 exons

Exon	Start	End
ENSE00001383093	37990779	37991314

Expression profiles

Bgee: expression breadth broad, 49 present calls, max score 95.50.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0405 / max 32.4781, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195928	0.0405	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.50	gold quality
sperm	CL:0000019	91.14	gold quality
left testis	UBERON:0004533	90.45	gold quality
right testis	UBERON:0004534	89.89	gold quality
male germ cell	CL:0000015	88.12	gold quality
testis	UBERON:0000473	87.18	gold quality
frontal pole	UBERON:0002795	60.41	gold quality
adult organism	UBERON:0007023	60.36	gold quality
middle frontal gyrus	UBERON:0002702	60.23	gold quality
amniotic fluid	UBERON:0000173	60.17	gold quality
paraflocculus	UBERON:0005351	59.90	gold quality
endometrium epithelium	UBERON:0004811	56.90	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.84	gold quality
thymus	UBERON:0002370	50.19	gold quality
quadriceps femoris	UBERON:0001377	50.06	gold quality
metanephric glomerulus	UBERON:0004736	49.61	gold quality
vastus lateralis	UBERON:0001379	49.57	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
oviduct epithelium	UBERON:0004804	48.47	gold quality
epithelial cell of pancreas	CL:0000083	48.40	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting H2AP, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-6811-3P	98.62	66.54	944
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-6500-3P	97.42	67.20	867
HSA-MIR-490-5P	96.75	65.81	661

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	H2ap	ENSMUSG00000040456
rattus_norvegicus	H2ap	ENSRNOG00000089464

Protein

Protein identifiers

Huntingtin-interacting protein M — O75409 (reviewed: O75409)

Alternative names: Histone H2A.P, Huntingtin yeast partner M

All UniProt accessions (1): O75409

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. May interact with the N-terminus of HD.

RefSeq proteins (1): NP_036406* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009072	Histone-fold	Homologous_superfamily

UniProt features (6 total): region of interest 2, compositionally biased region 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75409-F1	66.02	0.14

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 33 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_CHROMATIN_REMODELING, GOBP_HETEROCHROMATIN_ORGANIZATION, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOCC_PROTEIN_DNA_COMPLEX, GOMF_PROTEIN_HETERODIMERIZATION_ACTIVITY, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, MODULE_49, DUTERTRE_ESTRADIOL_RESPONSE_6HR_UP, chrXp11, GSE14000_TRANSLATED_RNA_VS_MRNA_16H_LPS_DC_UP, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION, GOCC_NUCLEOSOME

GO Biological Process (1): heterochromatin formation (GO:0031507)

GO Molecular Function (3): structural constituent of chromatin (GO:0030527), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (2): nucleosome (GO:0000786), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin	2
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1
structural molecule activity	1
protein dimerization activity	1
binding	1
protein-DNA complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

962 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H2AP	TP53BP1	Q12888	549
H2AP	FAM237B	A0A1B0GVD1	514
H2AP	HTT	P42858	485
H2AP	FAM171B	Q6P995	481
H2AP	A0A0A6YYL1	A0A0A6YYL1	445
H2AP	ZNF839	A8K0R7	426
H2AP	H2AB1	P0C5Y9	373
H2AP	TMEM243	Q9BU79	350
H2AP	GDE1	Q9NZC3	340
H2AP	SH2D4A	Q9H788	327
H2AP	GPATCH1	Q9BRR8	322
H2AP	RAD9A	Q99638	320
H2AP	RIPPLY3	P57055	305
H2AP	H1-7	Q75WM6	303
H2AP	H2AC20	Q16777	299
H2AP	H2AC19	P20670	299

IntAct

78 interactions, top by confidence:

A	B	Type	Score
H2AP	MYOG	psi-mi:“MI:0915”(physical association)	0.720
CEP44	H2AP	psi-mi:“MI:0915”(physical association)	0.720
H2AP	CEP44	psi-mi:“MI:0915”(physical association)	0.720
H2AP	SIX1	psi-mi:“MI:0915”(physical association)	0.670
H2AP	CENPH	psi-mi:“MI:0915”(physical association)	0.670
H2AP	HTT	psi-mi:“MI:0915”(physical association)	0.670
H2AP	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
	H2AP	psi-mi:“MI:0915”(physical association)	0.560
MAGEB4	H2AP	psi-mi:“MI:0915”(physical association)	0.560
H2AP	APOE	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (87): HYPM (Two-hybrid), CEP44 (Two-hybrid), HYPM (Two-hybrid), HYPM (Two-hybrid), HYPM (Two-hybrid), HYPM (Two-hybrid), HYPM (Two-hybrid), HYPM (Two-hybrid), HYPM (Two-hybrid), HYPM (Two-hybrid), HYPM (Two-hybrid), USP28 (Affinity Capture-MS), RAB5A (Affinity Capture-MS), ZFPL1 (Affinity Capture-MS), NCAPG (Affinity Capture-MS)

ESM2 similar proteins: A3RM20, A4QE81, A6ZMG4, A8C8J5, B2IUW7, B3LLZ8, B7KF62, C7GWA2, C8ZEW0, O66665, O75409, O94293, P02892, P03872, P04376, P09297, P18571, P21299, P26654, P30890, P38302, P40155, Q04438, Q06091, Q07FI4, Q09223, Q0GBX8, Q22058, Q28103, Q289M6, Q2Y2M2, Q3MBJ9, Q4R717, Q5GSP9, Q5H943, Q5WFM7, Q6C070, Q6WB97, Q6X1D3, Q6ZQV5

Diamond homologs: O75409, Q9CR04, A0A0D2UG83, A0A3B3IU63, A5DXS8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	15
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
599548	NM_012274.2(H2AP):c.321_322del (p.Phe107fs)	Pathogenic

SpliceAI

210 predictions. Top by Δscore:

Variant	Effect	Δscore
X:37990854:GAACT:G	donor_gain	0.8700
X:37990859:G:GG	donor_gain	0.7900
X:37990987:A:AG	donor_gain	0.7700
X:37990987:A:G	donor_gain	0.7500
X:37990918:GTCCC:G	donor_gain	0.7400
X:37990919:TCCCT:T	donor_gain	0.7400
X:37991300:G:GT	donor_gain	0.7400
X:37990960:G:GT	donor_gain	0.6800
X:37991069:G:GG	donor_gain	0.6800
X:37990964:TCCA:T	donor_gain	0.6700
X:37991299:GGAT:G	donor_gain	0.6700
X:37990952:A:G	donor_gain	0.6600
X:37991037:GCGG:G	donor_gain	0.6600
X:37991068:A:AG	donor_gain	0.6300
X:37991117:G:GG	donor_gain	0.6300
X:37990912:C:G	donor_gain	0.6000
X:37991311:A:AG	donor_gain	0.6000
X:37990856:ACT:A	donor_gain	0.5900
X:37991022:T:A	acceptor_gain	0.5900
X:37990920:C:A	donor_gain	0.5700
X:37991137:A:AG	donor_gain	0.5700
X:37991138:G:GG	donor_gain	0.5700
X:37991164:G:GC	acceptor_gain	0.5700
X:37990974:GA:G	donor_gain	0.5600
X:37991036:AGCGG:A	donor_loss	0.5500
X:37991038:CGGG:C	donor_loss	0.5500
X:37991039:GGG:G	donor_loss	0.5500
X:37991041:G:A	donor_loss	0.5500
X:37991042:T:A	donor_loss	0.5500
X:37991136:GA:G	donor_gain	0.5500

AlphaMissense

795 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:37991018:T:C	L60P	0.875
X:37990930:T:C	F31L	0.867
X:37990932:C:A	F31L	0.867
X:37990932:C:G	F31L	0.867
X:37991020:G:C	A61P	0.810
X:37991009:T:C	L57P	0.796
X:37991039:G:C	R67P	0.773
X:37991030:T:G	I64S	0.752
X:37991053:G:C	A72P	0.741
X:37991030:T:A	I64N	0.711
X:37991018:T:A	L60H	0.688
X:37991030:T:C	I64T	0.681
X:37991018:T:G	L60R	0.667
X:37990997:T:C	L53P	0.666
X:37991009:T:A	L57H	0.658
X:37991000:T:C	L54P	0.645
X:37991041:G:C	V68L	0.623
X:37991041:G:T	V68L	0.623
X:37991152:T:C	F105L	0.595
X:37991154:T:A	F105L	0.595
X:37991154:T:G	F105L	0.595
X:37991021:C:A	A61D	0.586
X:37991051:A:G	E71G	0.583
X:37991051:A:T	E71V	0.581
X:37991042:T:A	V68E	0.573
X:37991034:G:A	M65I	0.564
X:37991034:G:C	M65I	0.564
X:37991034:G:T	M65I	0.564

dbSNP variants (sampled 300 via entrez): RS1001220367 (X:37990120 C>G,T), RS1001272498 (X:37989908 T>A), RS1001645344 (X:37990274 A>C), RS1003229950 (X:37988909 G>T), RS1005591754 (X:37991412 G>C,T), RS1006213802 (X:37990074 C>T), RS1007460864 (X:37989588 A>G), RS1007675161 (X:37989977 A>G), RS1010034377 (X:37990169 G>A), RS1011503735 (X:37990535 G>A), RS1011864202 (X:37990242 A>G), RS1015992302 (X:37989539 G>A), RS1016934777 (X:37991751 C>T), RS1017275121 (X:37990005 T>C), RS1017400741 (X:37991380 G>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Coal	increases abundance, increases expression	1
Smoke	increases abundance, increases expression	1

Clinical trials (associated diseases)

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