HIP1

Summary

HIP1 (huntingtin interacting protein 1, HGNC:4913) is a protein-coding gene on chromosome 7q11.23, encoding Huntingtin-interacting protein 1 (O00291). Plays a role in clathrin-mediated endocytosis and trafficking.

The product of this gene is a membrane-associated protein that functions in clathrin-mediated endocytosis and protein trafficking within the cell. The encoded protein binds to the huntingtin protein in the brain; this interaction is lost in Huntington’s disease. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3092 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 224 total
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 3 cancer types
• MANE Select transcript: NM_005338

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4913
Approved symbol	HIP1
Name	huntingtin interacting protein 1
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Aliases	ILWEQ
Ensembl gene	ENSG00000127946
Ensembl biotype	protein_coding
OMIM	601767
Entrez	3092

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000336926, ENST00000404944, ENST00000420909, ENST00000434438, ENST00000479835, ENST00000485723, ENST00000616821, ENST00000857520, ENST00000949545

RefSeq mRNA: 4 — MANE Select: NM_005338 NM_001243198, NM_001382444, NM_001382445, NM_005338

CCDS: CCDS34669, CCDS59060, CCDS94128

Canonical transcript exons

ENST00000336926 — 31 exons

Exon	Start	End
ENSE00000876853	75539323	75539431
ENSE00000876855	75541919	75541980
ENSE00000876857	75542851	75542974
ENSE00000876864	75546939	75547032
ENSE00000876866	75547755	75547813
ENSE00000876867	75548891	75549001
ENSE00000876869	75553453	75553589
ENSE00000876874	75554440	75554526
ENSE00000876882	75557654	75557770
ENSE00000876886	75558167	75558255
ENSE00000876899	75568199	75568256
ENSE00000876904	75581237	75581298
ENSE00000876907	75582075	75582151
ENSE00001127983	75573761	75573901
ENSE00001127999	75544695	75544800
ENSE00001146949	75563188	75563263
ENSE00001201185	75545088	75545188
ENSE00001201200	75554113	75554220
ENSE00001201226	75556710	75556811
ENSE00001241849	75555416	75555551
ENSE00001241987	75586753	75586833
ENSE00001351159	75592056	75592112
ENSE00001504633	75556026	75556169
ENSE00001504634	75592372	75592514
ENSE00001504636	75599184	75599247
ENSE00001703612	75738801	75738941
ENSE00001900211	75533298	75538224
ENSE00003515708	75561329	75561401
ENSE00003521931	75559732	75559915
ENSE00003529225	75562935	75563075
ENSE00003674769	75562073	75562170

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 94.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.0091 / max 150.0786, expressed in 1721 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84380	7.3010	1479
84377	3.5101	1158
84381	1.3633	840
84373	0.3940	252
84378	0.2579	122
84371	0.1228	37
84376	0.0541	14
84372	0.0059	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	94.46	gold quality
sural nerve	UBERON:0015488	93.99	gold quality
inferior vagus X ganglion	UBERON:0005363	93.92	gold quality
renal medulla	UBERON:0000362	93.05	gold quality
calcaneal tendon	UBERON:0003701	91.95	gold quality
subthalamic nucleus	UBERON:0001906	90.71	gold quality
left testis	UBERON:0004533	90.60	gold quality
lower lobe of lung	UBERON:0008949	90.21	gold quality
popliteal artery	UBERON:0002250	90.11	gold quality
tibial artery	UBERON:0007610	90.09	gold quality
right testis	UBERON:0004534	89.97	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.27	gold quality
right coronary artery	UBERON:0001625	89.05	gold quality
visceral pleura	UBERON:0002401	88.82	gold quality
spinal cord	UBERON:0002240	88.76	gold quality
aorta	UBERON:0000947	88.55	gold quality
saphenous vein	UBERON:0007318	88.49	gold quality
right lung	UBERON:0002167	88.26	gold quality
adrenal tissue	UBERON:0018303	88.11	gold quality
globus pallidus	UBERON:0001875	87.80	gold quality
testis	UBERON:0000473	87.75	gold quality
medial globus pallidus	UBERON:0002477	87.72	gold quality
coronary artery	UBERON:0001621	87.58	gold quality
descending thoracic aorta	UBERON:0002345	87.50	gold quality
left coronary artery	UBERON:0001626	87.49	gold quality
synovial joint	UBERON:0002217	87.46	gold quality
superior vestibular nucleus	UBERON:0007227	87.40	gold quality
germinal epithelium of ovary	UBERON:0001304	87.25	gold quality
ventral tegmental area	UBERON:0002691	87.09	gold quality
ganglionic eminence	UBERON:0004023	87.09	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	71.56
E-ANND-3	yes	10.12
E-MTAB-7249	no	175.94

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
AR	Repression
REST	Activation

Upstream regulators (CollecTRI, top): GLI2, GLI3, TFAP2A

miRNA regulators (miRDB)

242 targeting HIP1, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784

Literature-anchored findings (GeneRIF, showing 35)

• Results show that pro-apoptotic Hippi-Hip-1 heterodimers can recruit procaspase-8 into a complex of Hippi, Hip-1 and procaspase-8, and launch apoptosis through components of the ’extrinsic’ cell-death pathway. (PMID:11788820)
• HIP1 and HIP12 display differential binding to F-actin, AP2, and clathrin. Identification of a novel interaction with clathrin light chain. (PMID:11889126)
• huntingtin-interacting protein 1 is overexpressed in prostate and colon cancer and is critical for cellular survival (PMID:12163454)
• both HIP1r and HIP1 bind inositol lipids via their epsin N-terminal homology (ENTH) domains. (PMID:14732715)
• HIP1 has roles in endocytosis and receptor trafficking and in tumorigenesis (PMID:15059611)
• roles of Hip1 and Hip1R in affecting clathrin assembly and actin distribution are mediated by their interaction with the conserved sequence of clathrin light chain (PMID:15533940)
• The F-actin binding capacity of Hip1 is regulated by intrasteric occlusion of primary actin-binding determinants within the Hip1 I/LWEQ module. (PMID:15581353)
• HIP1 is a nucleocytoplasmic protein capable of associating with membranes and DNA response elements and regulating transcription. (PMID:16027218)
• neurotoxic signals of Hip1 transmit through the intrinsic mitochondrial apoptotic pathwaysand the formation of apoptosome complex (PMID:16979168)
• Human HIP1 transgenic Hip1/Hip1r knockout mice are completely free from dwarfism and spinal defects. (PMID:17452370)
• Crystal structure at 2.8 A of HIP1 coiled-coil domain reveals a charged surface suitable for HIP1 protein interactor (HIPPI). (PMID:18155047)
• Actin binding by Hip1 (huntingtin-interacting protein 1) and Hip1R (Hip1-related protein) is regulated by clathrin light chain (PMID:18790740)
• Data demonstrate HIP1’s role in pits maturation and formation of the coated vesicle, and its strong dependence on clathrin for membranal localization. (PMID:19626275)
• hydrogen-bond network and changes in coiled-coil monomer interaction suggest that the HIP1 coiled-coil domain is uniquely suited to allow conformational flexibility. (PMID:20179344)
• data characterize a neurodevelopmental and epilepsy syndrome that is likely caused by recurrent and nonrecurrent deletions, including HIP1 (PMID:21109226)
• Huntingtin-interacting protein 1 is a Merkel cell carcinoma marker that interacts with c-Kit (PMID:21697888)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• flexibility of the HIP1 coiled-coil domain is important for normal function and may lead to new insights into Huntington’s disease (PMID:22835334)
• Three neuronal proteins (Huntingtin interacting protein 1, neurofascin, and olfactomedin-like 2a) are novel components of podocyte major processes and their expression in glomerular crescents supports their role in crescent formation. (PMID:22913984)
• Identified a four-tyrosine “HIP1 phosphorylation motif” in the N-terminal region of HIP1 that is required for phosphorylation mediated by both EGFR and PDGFbetaR but not by the oncoproteins HIP1/PDGFbetaR (H/P), and TEL/PDGFbetaR (T/P). (PMID:23836884)
• SHON is a novel human oncogene with predictive utility in ER(+) breast cancer, perhaps offering a simple biomarker to predict the therapeutic efficacy of antiestrogen therapy in patients with breast cancer. (PMID:24296488)
• HIP1-ALK-rearranged tumor is sensitive to treatment with crizotinib, implicating HIP1-ALKas an oncogenic driver of lung tumorigenesis (PMID:24496003)
• HIP1-ALK, a novel fusion protein is associated with lung adenocarcinoma. (PMID:24518094)
• SHON plays an important role in EMT and contributes to breast cancer progression. (PMID:25082541)
• HIP1 deletion is not involved in Williams-Beuren syndrome. (PMID:26437767)
• Huntingtin-interacting protein-1 (HIP1) is known to play a role in tumorigenesis. metastasis. Read More: http://www.atsjournals.org/doi/full/10.1164/rccm.201412-2226OC#.V8DF69LrtNs (PMID:26595459)
• HIP1 gene expression might serve as a reliable predictor for overall survival in acute myeloid leukemia patients. (PMID:28452374)
• After HIP1 expression was blocked by siRNAs, EGFR endocytosis was accelerated and this effect was dependent on the EGF concentration. This endocytosis was colocalized with clathrin expression. These findings indicate that the inhibition of HIP1 can accelerate the endocytosis and degradation of EGFR (PMID:29039605)
• Data suggest that GLP1R signaling in pancreatic beta-cells leading to insulin secretion involves interactions of GLP1R with HIP1, SNX1, and SNX27; HIP1 appears to regulate coupling of cell surface GLP1R activation with endocytosis; SNX1 and SNX27 appear to control balance between GLP1R plasma membrane recycling and lysosomal degradation. (PMID:29284659)
• HIP1 is a new arthritis severity gene and a potential novel prognostic biomarker and target for therapy in rheumatoid arthritis. (PMID:30049830)
• Gdpd3 compensates for Hip1 loss. (PMID:30224518)
• White matter DNA methylation profiling reveals deregulation of HIP1, LMAN2, MOBP, and other loci in multiple system atrophy. (PMID:31535203)
• miR-1272 Exerts Tumor-Suppressive Functions in Prostate Cancer via HIP1 Suppression. (PMID:32069895)
• MOBP and HIP1 in multiple system atrophy: New alpha-synuclein partners in glial cytoplasmic inclusions implicated in the disease pathogenesis. (PMID:33368549)
• KIF1C and new Huntingtin-interacting protein 1 binding proteins regulate rheumatoid arthritis fibroblast-like synoviocytes’ phenotypes. (PMID:38726004)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	hip1	ENSDARG00000062972
mus_musculus	Hip1	ENSMUSG00000039959
rattus_norvegicus	Hip1	ENSRNOG00000001448
drosophila_melanogaster	Hip1	FBGN0036309
caenorhabditis_elegans	tag-138	WBGENE00006484
caenorhabditis_elegans		WBGENE00022717

Paralogs (1): HIP1R (ENSG00000130787)

Protein

Protein identifiers

Huntingtin-interacting protein 1 — O00291 (reviewed: O00291)

Alternative names: Huntingtin-interacting protein I

All UniProt accessions (2): O00291, C9JMG5

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in clathrin-mediated endocytosis and trafficking. Involved in regulating AMPA receptor trafficking in the central nervous system in an NMDA-dependent manner. Regulates presynaptic nerve terminal activity. Enhances androgen receptor (AR)-mediated transcription. May act as a proapoptotic protein that induces cell death by acting through the intrinsic apoptosis pathway. Binds 3-phosphoinositides (via ENTH domain). May act through the ENTH domain to promote cell survival by stabilizing receptor tyrosine kinases following ligand-induced endocytosis. May play a functional role in the cell filament networks. May be required for differentiation, proliferation, and/or survival of somatic and germline progenitors.

Subunit / interactions. Homodimer. Binds actin. Binds HTT (via N-terminus). This interaction is restricted to the brain. Binds to IFT57. In normal conditions, it poorly interacts with IFT57, HIP1 being strongly associated with HTT. However, in mutant HTT proteins with a long poly-Gln region, interaction between HTT and HIP1 is inhibited, promoting the interaction between HIP1 and IFT57. Interacts with CLTB (via N-terminus). Interacts (via coiled coil domain) with AR. Interacts with AP2A1, AP2A2, CLTC and HIP1R. Interacts with GRIA1, GRIN2A and GRIN2B.

Subcellular location. Cytoplasm. Nucleus. Endomembrane system. Cytoplasmic vesicle. Clathrin-coated vesicle membrane.

Tissue specificity. Ubiquitously expressed with the highest level in brain. Expression is up-regulated in prostate and colon cancer.

Disease relevance. A chromosomal aberration involving HIP1 is found in a form of chronic myelomonocytic leukemia (CMML). Translocation t(5;7)(q33;q11.2) with PDGFRB. The chimeric HIP1-PDGFRB transcript results from an in-frame fusion of the two genes. The reciprocal PDGFRB-HIP1 transcript is not expressed.

Domain organisation. The pseudo DED region (pDED) mediates the interaction with IFT57. Binds F-actin via the talin-like I/LWEQ domain.

Miscellaneous. The affinity of the huntingtin protein-HIP1 interaction is inversely correlated to the length of the polyglutamine tract added to the huntingtin protein in Huntington disease.

Similarity. Belongs to the SLA2 family.

Isoforms (4)

UniProt ID	Names	Canonical?
O00291-1	HIP1-1	yes
O00291-2	HIP1-2
O00291-3	3
O00291-4	4

RefSeq proteins (4): NP_001230127, NP_001369373, NP_001369374, NP_005329* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002558	ILWEQ_dom	Domain
IPR008942	ENTH_VHS	Homologous_superfamily
IPR011417	ANTH_dom	Domain
IPR013809	ENTH	Domain
IPR030224	Sla2_fam	Family
IPR032422	HIP1_clath-bd	Domain
IPR035964	I/LWEQ_dom_sf	Homologous_superfamily

Pfam: PF01608, PF07651, PF16515

UniProt features (24 total): sequence conflict 5, mutagenesis site 4, helix 3, region of interest 3, domain 2, splice variant 2, chain 1, sequence variant 1, turn 1, coiled-coil region 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3I00	X-RAY DIFFRACTION	2.3
2NO2	X-RAY DIFFRACTION	2.8
2QA7	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00291-F1	80.84	0.44

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 338

Mutagenesis-validated functional residues (4):

Position	Phenotype
56	abolishes 3-phosphoinositide-binding; when associated with e-58.
58	abolishes 3-phosphoinositide-binding; when associated with e-56.
432	abolishes hip1-induced cell death.
1005	reduces ar-induced nuclear translocation.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-9700645	ALK mutants bind TKIs
R-HSA-9725370	Signaling by ALK fusions and activated point mutants

MSigDB gene sets: 354 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, BOYAULT_LIVER_CANCER_SUBCLASS_G2, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_CLATHRIN_COAT_ASSEMBLY, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_POSITIVE_REGULATION_OF_RECEPTOR_MEDIATED_ENDOCYTOSIS, CAGCTG_AP4_Q5, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GTGCCTT_MIR506, GOBP_REGULATION_OF_RECEPTOR_INTERNALIZATION

GO Biological Process (16): endocytosis (GO:0006897), apoptotic process (GO:0006915), actin filament organization (GO:0007015), regulation of endocytosis (GO:0030100), cell differentiation (GO:0030154), regulation of apoptotic process (GO:0042981), positive regulation of epidermal growth factor receptor signaling pathway (GO:0045742), positive regulation of receptor-mediated endocytosis (GO:0048260), clathrin coat assembly (GO:0048268), protein stabilization (GO:0050821), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), apoptotic signaling pathway (GO:0097190), regulation of postsynaptic neurotransmitter receptor internalization (GO:0099149), presynaptic modulation of chemical synaptic transmission (GO:0099171), neurotransmitter receptor transport (GO:0099637), positive regulation of platelet-derived growth factor receptor-beta signaling pathway (GO:2000588)

GO Molecular Function (17): epidermal growth factor receptor binding (GO:0005154), structural constituent of cytoskeleton (GO:0005200), clathrin binding (GO:0030276), clathrin light chain binding (GO:0032051), phosphatidylinositol-3-phosphate binding (GO:0032266), phosphatidylinositol binding (GO:0035091), glutamate receptor binding (GO:0035254), AP-2 adaptor complex binding (GO:0035612), clathrin-cargo adaptor activity (GO:0035615), protein homodimerization activity (GO:0042803), phosphatidylinositol-3,4-bisphosphate binding (GO:0043325), protein heterodimerization activity (GO:0046982), actin filament binding (GO:0051015), phosphatidylinositol-3,5-bisphosphate binding (GO:0080025), actin binding (GO:0003779), protein binding (GO:0005515), phospholipid binding (GO:0005543)

GO Cellular Component (19): acrosomal vesicle (GO:0001669), nucleus (GO:0005634), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), cytoskeleton (GO:0005856), membrane (GO:0016020), clathrin-coated vesicle (GO:0030136), clathrin-coated vesicle membrane (GO:0030665), cortical actin cytoskeleton (GO:0030864), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), Schaffer collateral - CA1 synapse (GO:0098685), presynapse (GO:0098793), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), endomembrane system (GO:0012505), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by ALK in cancer	2
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	8
synapse	4
cytoplasm	3
apoptotic process	2
clathrin binding	2
phosphatidylinositol phosphate binding	2
protein-containing complex binding	2
protein dimerization activity	2
phosphatidylinositol bisphosphate binding	2
intracellular membrane-bounded organelle	2
sperm flagellum	2
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
endocytosis	1
regulation of cellular component organization	1
regulation of vesicle-mediated transport	1
cellular developmental process	1
regulation of programmed cell death	1
epidermal growth factor receptor signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1
positive regulation of ERBB signaling pathway	1
receptor-mediated endocytosis	1
positive regulation of endocytosis	1
regulation of receptor-mediated endocytosis	1
protein-containing complex assembly	1
regulation of protein stability	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
signal transduction	1
regulation of receptor internalization	1
regulation of biological quality	1
postsynaptic neurotransmitter receptor internalization	1

Protein interactions and networks

STRING

840 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HIP1	IFT57	Q9NWB7	562
HIP1	PTCH1	Q13635	480
HIP1	PTCH2	Q9Y6C5	479
HIP1	GLI1	P08151	473
HIP1	SLA2	Q9H6Q3	452
HIP1	HIP1R	O75146	435
HIP1	SMO	Q99835	419
HIP1	SUFU	Q9UMX1	419
HIP1	SHH	Q15465	398
HIP1	HHIPL2	Q6UWX4	396
HIP1	HTT	P42858	389
HIP1	CLTB	P09497	351
HIP1	GAK	O14976	350
HIP1	GLI2	P10070	349
HIP1	WIPF2	Q8TF74	348

IntAct

331 interactions, top by confidence:

A	B	Type	Score
HIP1	HTT	psi-mi:“MI:0915”(physical association)	0.810
HIP1	LITAF	psi-mi:“MI:0915”(physical association)	0.720
DAZAP2	HIP1	psi-mi:“MI:0915”(physical association)	0.670
HIP1	GLS2	psi-mi:“MI:0915”(physical association)	0.670
HIP1R	HIP1	psi-mi:“MI:0914”(association)	0.640
REL	HIP1	psi-mi:“MI:0915”(physical association)	0.560
HIP1	CFAP53	psi-mi:“MI:0915”(physical association)	0.560
HIP1	TCEANC	psi-mi:“MI:0915”(physical association)	0.560
HIP1	FAM168A	psi-mi:“MI:0915”(physical association)	0.560
HIP1	LNX1	psi-mi:“MI:0915”(physical association)	0.560
HIP1	RAD23B	psi-mi:“MI:0915”(physical association)	0.560
HIP1	TCEA2	psi-mi:“MI:0915”(physical association)	0.560
HIP1	EHHADH	psi-mi:“MI:0915”(physical association)	0.560
HIP1	SYT17	psi-mi:“MI:0915”(physical association)	0.560
HIP1	RPRM	psi-mi:“MI:0915”(physical association)	0.560
HIP1	CYRIB	psi-mi:“MI:0915”(physical association)	0.560
TRIM23	HIP1	psi-mi:“MI:0915”(physical association)	0.560
HIP1	BAAT	psi-mi:“MI:0915”(physical association)	0.560
HIP1		psi-mi:“MI:0915”(physical association)	0.560
CDKN2C	HIP1	psi-mi:“MI:0915”(physical association)	0.560
HIP1	CLTA	psi-mi:“MI:0915”(physical association)	0.560
HIP1	COL2A1	psi-mi:“MI:0915”(physical association)	0.560
HIP1	CTNNB1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (149): HIP1 (Two-hybrid), REL (Two-hybrid), DAZAP2 (Two-hybrid), HIP1 (Biochemical Activity), HIP1 (Affinity Capture-MS), HIP1 (Affinity Capture-MS), HIP1 (Proximity Label-MS), HIP1 (Affinity Capture-MS), HIP1 (Affinity Capture-MS), HIP1 (Affinity Capture-MS), HIP1 (Affinity Capture-MS), HIP1 (Affinity Capture-MS), CLTC (Co-localization), HIP1 (Biochemical Activity), EGFR (Affinity Capture-Western)

ESM2 similar proteins: A0PJP4, A2VDP1, A5D7M3, B2RW38, D3ZUQ0, F1QNW4, O00291, O14645, O43805, O75146, O75150, O95995, Q17QG3, Q26630, Q3U319, Q499U4, Q4FZV3, Q4R3K5, Q4R7K7, Q4R7Y8, Q4V328, Q5DTM8, Q5E9C3, Q5EBL4, Q5RAU7, Q5T655, Q5VTR2, Q5ZLS3, Q60779, Q68CZ1, Q6DGZ3, Q6GN86, Q7XJ96, Q7Z3E2, Q8BKE9, Q8BR07, Q8BVN8, Q8C9S4, Q8CG73, Q8CJB9

Diamond homologs: O00291, O75146, Q02328, Q8VD75, Q9JKY5, Q9P6L5, A0A3G2LGI8, Q54K81, P0CE95, P33338

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
HIP1	“down-regulates quantity by repression”	AR	“transcriptional regulation”
HIP1	“up-regulates quantity by expression”	REST	“transcriptional regulation”
HIP1	up-regulates	Cell_death
BCL2L1	down-regulates	HIP1
HIP1	up-regulates	Apoptosis
“AP-2 complex”	“up-regulates activity”	HIP1	binding

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 3 cancer types — MBL, UCS, UTUC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	131
Likely benign	26
Benign	18

Top pathogenic / likely-pathogenic (0)

SpliceAI

5288 predictions. Top by Δscore:

Variant	Effect	Δscore
7:75539317:GCTTA:G	donor_loss	1.0000
7:75539318:CTTA:C	donor_loss	1.0000
7:75539319:TTACC:T	donor_loss	1.0000
7:75539320:TACCT:T	donor_loss	1.0000
7:75539321:A:AT	donor_loss	1.0000
7:75539322:C:CA	donor_loss	1.0000
7:75539427:CTAAC:C	acceptor_gain	1.0000
7:75539428:TAAC:T	acceptor_gain	1.0000
7:75541916:CA:C	donor_loss	1.0000
7:75541917:A:C	donor_loss	1.0000
7:75541977:TTGT:T	acceptor_gain	1.0000
7:75541978:TGT:T	acceptor_gain	1.0000
7:75541978:TGTCT:T	acceptor_loss	1.0000
7:75541979:GT:G	acceptor_gain	1.0000
7:75541980:TCTG:T	acceptor_loss	1.0000
7:75541981:C:CC	acceptor_gain	1.0000
7:75541982:T:A	acceptor_loss	1.0000
7:75541989:A:C	acceptor_gain	1.0000
7:75542845:GGCTA:G	donor_loss	1.0000
7:75542846:GCTAC:G	donor_loss	1.0000
7:75542847:CTA:C	donor_loss	1.0000
7:75542848:TACCT:T	donor_loss	1.0000
7:75542850:C:CT	donor_loss	1.0000
7:75542850:CCTGT:C	donor_gain	1.0000
7:75544800:CCTGA:C	acceptor_gain	1.0000
7:75545086:A:AC	donor_gain	1.0000
7:75545086:ACAC:A	donor_gain	1.0000
7:75545086:ACACC:A	donor_loss	1.0000
7:75545087:C:CA	donor_gain	1.0000
7:75545087:CA:C	donor_gain	1.0000

AlphaMissense

6838 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:75545144:C:A	W868C	1.000
7:75545144:C:G	W868C	1.000
7:75545146:A:G	W868R	1.000
7:75545146:A:T	W868R	1.000
7:75568220:C:G	R261P	1.000
7:75568226:C:G	R259P	1.000
7:75568238:A:G	L255P	1.000
7:75573769:A:G	L246P	1.000
7:75573774:G:C	F244L	1.000
7:75573774:G:T	F244L	1.000
7:75573776:A:G	F244L	1.000
7:75592422:A:G	W93R	1.000
7:75592422:A:T	W93R	1.000
7:75539391:C:G	R998P	0.999
7:75544711:A:G	L917P	0.999
7:75558177:A:G	L485P	0.999
7:75558219:A:G	L471P	0.999
7:75563062:A:G	F298S	0.999
7:75563231:A:G	L279P	0.999
7:75568216:G:C	F262L	0.999
7:75568216:G:T	F262L	0.999
7:75568217:A:G	F262S	0.999
7:75568218:A:G	F262L	0.999
7:75568230:G:C	H258D	0.999
7:75568233:C:G	G257R	0.999
7:75568238:A:T	L255Q	0.999
7:75568253:A:G	L250P	0.999
7:75573767:G:C	H247D	0.999
7:75573769:A:T	L246H	0.999
7:75573778:A:G	L243P	0.999

dbSNP variants (sampled 300 via entrez): RS1000058757 (7:75629396 A>C), RS1000075992 (7:75703169 C>T), RS1000109565 (7:75546182 G>A), RS1000130814 (7:75637491 T>C), RS1000231069 (7:75591955 G>A,T), RS1000252923 (7:75551730 C>T), RS1000274467 (7:75620188 C>T), RS1000380617 (7:75722606 T>C), RS1000400771 (7:75681386 C>T), RS1000414109 (7:75637125 C>T), RS1000425903 (7:75557588 C>T), RS1000444661 (7:75586020 C>G,T), RS1000456963 (7:75557279 C>T), RS1000520206 (7:75674244 T>C), RS1000589566 (7:75716086 G>A)

Disease associations

OMIM: gene MIM:601767 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST001055_2	Alcoholism (12-month weekly alcohol consumption)	7.000000e-06
GCST002498_5	Age-related nuclear cataracts	5.000000e-06
GCST002783_450	Body mass index	2.000000e-10
GCST002783_486	Body mass index	6.000000e-10
GCST002783_90	Body mass index	9.000000e-08
GCST003599_16	Systemic lupus erythematosus	1.000000e-12
GCST004495_135	BMI (adjusted for smoking behaviour)	5.000000e-06
GCST004495_136	BMI (adjusted for smoking behaviour)	6.000000e-08
GCST004497_107	Body mass index (joint analysis main effects and smoking interaction)	2.000000e-07
GCST004499_42	BMI in non-smokers	2.000000e-07
GCST004557_10	Body mass index	5.000000e-08
GCST004557_189	Body mass index	3.000000e-07
GCST004558_130	Body mass index (joint analysis main effects and physical activity interaction)	2.000000e-06
GCST004558_7	Body mass index (joint analysis main effects and physical activity interaction)	4.000000e-07
GCST004559_190	Body mass index in physically active individuals	6.000000e-06
GCST004559_5	Body mass index in physically active individuals	8.000000e-07
GCST004618_70	White blood cell count (basophil)	3.000000e-13
GCST004631_24	Basophil percentage of white cells	1.000000e-12
GCST004634_32	Basophil percentage of granulocytes	2.000000e-11
GCST004904_37	Body mass index	1.000000e-10
GCST006103_13	Interleukin-6 levels	1.000000e-06
GCST006802_1	Body mass index	2.000000e-06
GCST008361_9	Response to cognitive-behavioural therapy in major depressive disorder	6.000000e-06
GCST90002379_150	Basophil count	8.000000e-34
GCST90002380_46	Basophil percentage of white cells	5.000000e-36

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes
EFO:0007995	basophil percentage of granulocytes
EFO:0004810	interleukin-6 measurement
EFO:0007820	cognitive behavioural therapy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

52 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	decreases expression, affects expression, affects cotreatment	4
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
Arsenic	decreases expression, affects methylation, decreases methylation, increases abundance, affects cotreatment	3
bisphenol A	affects cotreatment, increases methylation, decreases expression, decreases methylation	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases expression	2
Tretinoin	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
kojic acid	increases expression	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
aflatoxin B2	decreases methylation	1
nickel sulfate	increases expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
3-deazaneplanocin	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
apicidin	increases expression	1
scriptaid	increases expression	1
pinostrobin	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_DX43	HAP1 HIP1 (-) HIP1R (-) 1	Cancer cell line	Male
CVCL_DX44	HAP1 HIP1 (-) HIP1R (-) 2	Cancer cell line	Male
CVCL_DX45	HAP1 HIP1 (-) HIP1R (-) 3	Cancer cell line	Male
CVCL_SR40	HAP1 HIP1 (-) 1	Cancer cell line	Male
CVCL_XP55	HAP1 HIP1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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