HIP1R

Summary

HIP1R (huntingtin interacting protein 1 related, HGNC:18415) is a protein-coding gene on chromosome 12q24.31, encoding Huntingtin-interacting protein 1-related protein (O75146). Component of clathrin-coated pits and vesicles, that may link the endocytic machinery to the actin cytoskeleton.

Enables several functions, including phosphatidylinositol phosphate binding activity; phosphatidylinositol-3,4-bisphosphate binding activity; and protein homodimerization activity. Involved in several processes, including positive regulation of signal transduction; protein stabilization; and regulation of organelle organization. Located in clathrin-coated vesicle; cytosol; and ruffle membrane.

Source: NCBI Gene 9026 — RefSeq curated summary.

At a glance

• GWAS associations: 34
• Clinical variants (ClinVar): 232 total
• MANE Select transcript: NM_003959

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18415
Approved symbol	HIP1R
Name	huntingtin interacting protein 1 related
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0655, HIP3, HIP12, FLJ14000, ILWEQ
Ensembl gene	ENSG00000130787
Ensembl biotype	protein_coding
OMIM	605613
Entrez	9026

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 11 protein_coding, 7 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000253083, ENST00000452196, ENST00000535012, ENST00000535831, ENST00000536617, ENST00000536772, ENST00000536847, ENST00000537322, ENST00000538236, ENST00000541712, ENST00000851676, ENST00000851677, ENST00000851678, ENST00000851679, ENST00000851680, ENST00000933911, ENST00000933912, ENST00000933913, ENST00000944683

RefSeq mRNA: 3 — MANE Select: NM_003959 NM_001303097, NM_001303099, NM_003959

CCDS: CCDS31922

Canonical transcript exons

ENST00000253083 — 32 exons

Exon	Start	End
ENSE00000895217	122857021	122857215
ENSE00000895234	122860047	122860077
ENSE00000895237	122860148	122860210
ENSE00000895246	122858102	122858249
ENSE00001188647	122858838	122858945
ENSE00001188648	122858349	122858435
ENSE00001292069	122861706	122862961
ENSE00002237540	122835457	122835643
ENSE00003473946	122856256	122856344
ENSE00003495445	122854043	122854183
ENSE00003504025	122861131	122861192
ENSE00003513863	122861308	122861514
ENSE00003517719	122855265	122855405
ENSE00003529022	122856432	122856548
ENSE00003546425	122855831	122855903
ENSE00003548314	122854905	122854962
ENSE00003569442	122850835	122850911
ENSE00003578427	122860423	122860523
ENSE00003585466	122848796	122848852
ENSE00003591658	122860679	122860784
ENSE00003606431	122859772	122859830
ENSE00003634936	122851236	122851297
ENSE00003639541	122859061	122859197
ENSE00003649800	122855551	122855612
ENSE00003654940	122849875	122849955
ENSE00003658433	122848031	122848094
ENSE00003658968	122848466	122848608
ENSE00003660753	122856625	122856726
ENSE00003677752	122855053	122855128
ENSE00003678357	122860916	122861039
ENSE00003687787	122855980	122856163
ENSE00003692656	122859426	122859536

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 97.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.1370 / max 536.2809, expressed in 1681 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128539	18.2413	1625
128538	1.7645	596
128537	0.9948	412
128534	0.9323	322
128540	0.7692	414
128535	0.1448	80
128536	0.1399	63
128541	0.0986	35
128533	0.0515	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	97.80	gold quality
inferior olivary complex	UBERON:0002127	97.51	gold quality
metanephros cortex	UBERON:0010533	97.45	gold quality
skin of leg	UBERON:0001511	97.13	gold quality
spinal cord	UBERON:0002240	96.95	gold quality
right frontal lobe	UBERON:0002810	96.63	gold quality
body of pancreas	UBERON:0001150	96.60	gold quality
amygdala	UBERON:0001876	96.52	gold quality
skin of abdomen	UBERON:0001416	96.45	gold quality
adenohypophysis	UBERON:0002196	95.98	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	95.85	gold quality
hypothalamus	UBERON:0001898	95.79	gold quality
pituitary gland	UBERON:0000007	95.78	gold quality
pancreatic ductal cell	CL:0002079	95.70	gold quality
cranial nerve II	UBERON:0000941	95.70	gold quality
minor salivary gland	UBERON:0001830	95.64	gold quality
saliva-secreting gland	UBERON:0001044	95.56	gold quality
substantia nigra	UBERON:0002038	95.53	gold quality
cingulate cortex	UBERON:0003027	95.47	gold quality
anterior cingulate cortex	UBERON:0009835	95.40	gold quality
midbrain	UBERON:0001891	95.15	gold quality
cortical plate	UBERON:0005343	95.00	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.96	gold quality
Ammon’s horn	UBERON:0001954	94.90	gold quality
lower esophagus mucosa	UBERON:0035834	94.89	gold quality
inferior vagus X ganglion	UBERON:0005363	94.75	gold quality
zone of skin	UBERON:0000014	94.71	gold quality
putamen	UBERON:0001874	94.67	gold quality
corpus callosum	UBERON:0002336	94.60	gold quality
nucleus accumbens	UBERON:0001882	94.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	66.39
E-GEOD-84465	yes	27.38
E-ANND-3	yes	8.79

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXP1

miRNA regulators (miRDB)

32 targeting HIP1R, 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-4650-5P	99.98	64.69	999
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-3196	98.96	63.91	326
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-3180	98.46	64.68	348
HSA-MIR-3180-3P	98.46	64.68	348
HSA-MIR-6816-5P	98.46	64.35	364
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-4433A-3P	97.75	62.82	1435

Literature-anchored findings (GeneRIF, showing 21)

• HIP1 and HIP12 display differential binding to F-actin, AP2, and clathrin. Identification of a novel interaction with clathrin light chain. (HIP12) (PMID:11889126)
• both HIP1r and HIP1 bind inositol lipids via their epsin N-terminal homology (ENTH) domains (PMID:14732715)
• Hip1R has a role in making the interaction between actin and the endocytic machinery functional and transient (PMID:14742709)
• The F-actin binding capacity of Hip12 is regulated by intrasteric occlusion of primary actin-binding determinants within the Hip12 I/LWEQ module. (PMID:15581353)
• the stability of intergenerational transmission of a variable number tandem repeat (VNTR) polymorphism, found in the Huntingtin interacting protein-1 related gene (HIP12/HIP1R) that is mapped to the chromosome 12q24.31 region. (PMID:15588756)
• characterize the F-actin-binding region of HIP1R, termed the talin-HIP1/R/Sla2p actin-tethering C-terminal homology (THATCH) domain (PMID:16415883)
• Human HIP1 transgenic Hip1/Hip1r knockout mice are completely free from dwarfism and spinal defects. (PMID:17452370)
• Neuronal dysfunction in transgenic Caenorhabditis elegans expressing mutant N-terminal huntingtin is specifically enhanced by hipr-1 loss of function. (PMID:17928447)
• in mammalian cells CLCs function in intracellular membrane trafficking by acting as recruitment proteins for HIP1R, enabling HIP1R to regulate actin assembly on clathrin-coated structures (PMID:18165318)
• Actin binding by Hip1 (huntingtin-interacting protein 1) and Hip1R (Hip1-related protein) is regulated by clathrin light chain (PMID:18790740)
• This study provided the previously unknown function of HIP1R involved in the intrinsic cell death pathway and further explored possible mechanisms by which HIP1R induces cell death. (PMID:19255499)
• HIP1r plays an important role in regulating the attachment of spindle microtubules to chromosomes during mitosis, an event that is required for accurate congression and segregation of chromosomes. (PMID:21189155)
• STK39 (rs2102808) and CCDC62/HIP1R (rs12817488) do not appear to influence PD risk. (PMID:24312176)
• our findings support the conclusion that the rs12817488 in CCDC62/HIP1R polymorphism may increase the risk of Parkinson’s disease in the Chinese Han population. (PMID:25818163)
• We conclude that HIP1R expression is strongly indicative of survival in diffuse large B-cell lymphoma (PMID:26341140)
• HIP1R rescued miR-23b/-27b-mediated repression of migration in prostate cancer cells. HIP1R mRNA levels were decreased in seminal vesicle tissue from mice bearing miR-23b/-27b-transduced prostate cancer cell xenografts compared with scrambled controls, suggesting HIP1R is a key functional target of miR-23b/-27b. (PMID:26898757)
• HIP1R is a natural regulator of PD-L1 lysosomal degradation, and the functions of HIP1R relied on two sequence stretches- one involved in the interaction with PD-L1 and for the sorting to the lysosome. (PMID:30397328)
• There is coordinated action of myosin VI and CLCa at the apical surface where these proteins are essential for fission of clathrin-coated pits. Myosin VI and Huntingtin-interacting protein 1-related protein (Hip1R) are mutually exclusive interactors with CLCa, and suggest a model for the sequential function of myosin VI and Hip1R in actin-mediated clathrin-coated vesicle budding. (PMID:31672988)
• HIP1R acts as a tumor suppressor in gastric cancer by promoting cancer cell apoptosis and inhibiting migration and invasion through modulating Akt. (PMID:32548851)
• Flurbiprofen inhibits cell proliferation in thyroid cancer through interrupting HIP1R-induced endocytosis of PTEN. (PMID:35209947)
• DNA methylation and miR-92a-3p-mediated repression of HIP1R promotes pancreatic cancer progression by activating the PI3K/AKT pathway. (PMID:36811277)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	hip1ra	ENSDARG00000060627
danio_rerio	hip1rb	ENSDARG00000102458
mus_musculus	Hip1r	ENSMUSG00000000915
rattus_norvegicus	Hip1r	ENSRNOG00000001091
drosophila_melanogaster	Hip1	FBGN0036309
caenorhabditis_elegans	tag-138	WBGENE00006484
caenorhabditis_elegans		WBGENE00022717

Paralogs (1): HIP1 (ENSG00000127946)

Protein

Protein identifiers

Huntingtin-interacting protein 1-related protein — O75146 (reviewed: O75146)

Alternative names: Huntingtin-interacting protein 12

All UniProt accessions (2): O75146, H0YH66

UniProt curated annotations — full annotation on UniProt →

Function. Component of clathrin-coated pits and vesicles, that may link the endocytic machinery to the actin cytoskeleton. 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.

Subunit / interactions. Homodimer. Interacts with actin; homodimerization promotes actin binding. Interacts with CLTB. Interacts with HIP1. Interacts (via ENTH and I/LWEQ domains) with BCL2L10.

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

Tissue specificity. Brain, heart, kidney, pancreas, and liver, but not in lung or placenta.

Domain organisation. Binds F-actin via the talin-like I/LWEQ domain.

Similarity. Belongs to the SLA2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75146-1	1	yes
O75146-2	2

RefSeq proteins (1): NP_003950* (*=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 (34 total): helix 7, sequence variant 5, region of interest 5, compositionally biased region 4, mutagenesis site 4, domain 2, modified residue 2, splice variant 2, chain 1, turn 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1R0D	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75146-F1	81.92	0.50

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 (2): 1, 1017

Mutagenesis-validated functional residues (4):

Position	Phenotype
867	reduced acting binding.
871	reduced acting binding.
875	reduced acting binding.
922–924	strongly reduced actin binding.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-432722	Golgi Associated Vesicle Biogenesis
R-HSA-8856828	Clathrin-mediated endocytosis

MSigDB gene sets: 298 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN, RNGTGGGC_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_DIGESTION, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_ACID_SECRETION, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ACTIN_NUCLEATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_CLATHRIN_COAT_ASSEMBLY, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_RUFFLE, REACTOME_MEMBRANE_TRAFFICKING, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION

GO Biological Process (24): endocytosis (GO:0006897), receptor-mediated endocytosis (GO:0006898), actin filament organization (GO:0007015), regulation of endocytosis (GO:0030100), negative regulation of actin filament polymerization (GO:0030837), regulation of actin cytoskeleton organization (GO:0032956), negative regulation of Arp2/3 complex-mediated actin nucleation (GO:0034316), regulation of apoptotic process (GO:0042981), negative regulation of apoptotic process (GO:0043066), positive regulation of epidermal growth factor receptor signaling pathway (GO:0045742), clathrin coat assembly (GO:0048268), protein stabilization (GO:0050821), digestive system development (GO:0055123), regulation of gastric acid secretion (GO:0060453), intrinsic apoptotic signaling pathway (GO:0097193), postsynapse organization (GO:0099173), positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway (GO:1901030), positive regulation of clathrin coat assembly (GO:1905445), regulation of clathrin-dependent endocytosis (GO:2000369), positive regulation of platelet-derived growth factor receptor-beta signaling pathway (GO:2000588), positive regulation of transport (GO:0051050), positive regulation of cellular component organization (GO:0051130), membrane organization (GO:0061024), apoptotic signaling pathway (GO:0097190)

GO Molecular Function (16): phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), SH3 domain binding (GO:0017124), clathrin binding (GO:0030276), clathrin light chain binding (GO:0032051), phosphatidylinositol binding (GO:0035091), clathrin-cargo adaptor activity (GO:0035615), identical protein binding (GO:0042802), 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 (24): mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), postsynaptic density (GO:0014069), apical plasma membrane (GO:0016324), clathrin-coated vesicle (GO:0030136), clathrin-coated vesicle membrane (GO:0030665), cortical actin cytoskeleton (GO:0030864), ruffle membrane (GO:0032587), dendrite cytoplasm (GO:0032839), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), perinuclear region of cytoplasm (GO:0048471), synaptic membrane (GO:0097060), postsynaptic endocytic zone (GO:0098843), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell cortex (GO:0005938), endomembrane system (GO:0012505), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
trans-Golgi Network Vesicle Budding	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
cellular anatomical structure	4
phosphatidylinositol phosphate binding	3
phosphatidylinositol bisphosphate binding	3
endocytosis	2
actin cytoskeleton organization	2
apoptotic process	2
anion binding	2
protein binding	2
clathrin binding	2
protein dimerization activity	2
membrane	2
cell periphery	2
plasma membrane region	2
dendrite	2
postsynapse	2
synapse	2
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
supramolecular fiber organization	1
regulation of cellular component organization	1
regulation of vesicle-mediated transport	1
actin filament polymerization	1
regulation of actin filament polymerization	1
negative regulation of protein polymerization	1
negative regulation of cytoskeleton organization	1
negative regulation of supramolecular fiber organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
Arp2/3 complex-mediated actin nucleation	1
regulation of Arp2/3 complex-mediated actin nucleation	1
negative regulation of actin nucleation	1
regulation of programmed cell death	1
regulation of apoptotic process	1
negative 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

Protein interactions and networks

STRING

1288 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HIP1R	EPN2	O95208	965
HIP1R	SNAP91	O60641	959
HIP1R	EPN3	Q9H201	954
HIP1R	SLA2	Q9H6Q3	951
HIP1R	HTT	P42858	945
HIP1R	HCLS1	P14317	916
HIP1R	CTTN	Q14247	912
HIP1R	DAB2	P98082	834
HIP1R	CLTB	P09497	800
HIP1R	EPS15	P42566	756
HIP1R	CLTCL1	P53675	752
HIP1R	EPN1	Q9Y6I3	741
HIP1R	CCDC62	Q6P9F0	736
HIP1R	FCHO1	O14526	734
HIP1R	CLTC	Q00610	731

IntAct

131 interactions, top by confidence:

A	B	Type	Score
GLS2	HIP1	psi-mi:“MI:0914”(association)	0.670
HIP1R	HIP1	psi-mi:“MI:0914”(association)	0.640
STAMBPL1	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
SCN2B	EXOC5	psi-mi:“MI:0914”(association)	0.640
HIP1	HIP1R	psi-mi:“MI:0914”(association)	0.640
FAM234B	ABCD4	psi-mi:“MI:0914”(association)	0.620
HIP1R	HIP1R	psi-mi:“MI:0407”(direct interaction)	0.560
LRFN4	RIMOC1	psi-mi:“MI:0914”(association)	0.530
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
COMTD1	IFRD1	psi-mi:“MI:0914”(association)	0.530
TEX29	TOR1A	psi-mi:“MI:0914”(association)	0.530
CD274	TTI1	psi-mi:“MI:0914”(association)	0.530
SLC39A9	B4GALT5	psi-mi:“MI:0914”(association)	0.530
MFSD4A	HIP1R	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530

BioGRID (214): HIP1R (Affinity Capture-MS), HIP1R (Affinity Capture-MS), HIP1R (Affinity Capture-MS), HIP1R (Affinity Capture-MS), HIP1R (Affinity Capture-MS), HIP1R (Affinity Capture-MS), HIP1R (Affinity Capture-MS), HIP1R (Co-fractionation), HIP1R (Co-fractionation), HIP1R (Co-fractionation), HIP1R (Co-fractionation), HIP1R (Co-fractionation), HIP1R (Co-fractionation), HIP1R (Co-fractionation), HIP1R (Co-fractionation)

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, P0CE94, P0CE95, P33338, Q18685, Q54EW0, A0A3G2LGI8, Q54K81

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FOXP1	“down-regulates quantity by repression”	HIP1R	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 141 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Golgi Associated Vesicle Biogenesis	5	11.5×	7e-03
Clathrin-mediated endocytosis	8	7.8×	3e-03
Cargo recognition for clathrin-mediated endocytosis	6	7.2×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
clathrin coat assembly	6	44.0×	3e-06
clathrin-dependent endocytosis	5	24.0×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	186
Likely benign	11
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

4845 predictions. Top by Δscore:

Variant	Effect	Δscore
12:122848026:CACA:C	acceptor_loss	1.0000
12:122848028:CAGG:C	acceptor_loss	1.0000
12:122848029:A:AC	acceptor_loss	1.0000
12:122848029:A:AG	acceptor_gain	1.0000
12:122848030:G:A	acceptor_loss	1.0000
12:122848030:G:GG	acceptor_gain	1.0000
12:122848030:GGCC:G	acceptor_gain	1.0000
12:122848122:GAGT:G	donor_gain	1.0000
12:122848125:T:G	donor_gain	1.0000
12:122848609:G:GG	donor_gain	1.0000
12:122848848:TGTGG:T	donor_loss	1.0000
12:122848849:GTGG:G	donor_gain	1.0000
12:122848851:GGGT:G	donor_loss	1.0000
12:122848853:G:GG	donor_gain	1.0000
12:122849870:CACA:C	acceptor_loss	1.0000
12:122849871:A:AG	acceptor_gain	1.0000
12:122849871:ACAG:A	acceptor_gain	1.0000
12:122849871:ACAGG:A	acceptor_gain	1.0000
12:122849872:C:G	acceptor_gain	1.0000
12:122849872:CAGG:C	acceptor_loss	1.0000
12:122849873:A:AG	acceptor_gain	1.0000
12:122849873:A:T	acceptor_loss	1.0000
12:122849873:AG:A	acceptor_gain	1.0000
12:122849873:AGG:A	acceptor_gain	1.0000
12:122849874:G:GG	acceptor_gain	1.0000
12:122849874:GG:G	acceptor_gain	1.0000
12:122849874:GGG:G	acceptor_gain	1.0000
12:122849874:GGGA:G	acceptor_gain	1.0000
12:122849874:GGGAC:G	acceptor_gain	1.0000
12:122849955:GGTGG:G	donor_loss	1.0000

AlphaMissense

6967 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:122848558:T:A	W84R	1.000
12:122848558:T:C	W84R	1.000
12:122860465:T:A	W868R	1.000
12:122860465:T:C	W868R	1.000
12:122860467:G:C	W868C	1.000
12:122860467:G:T	W868C	1.000
12:122848037:A:C	S34R	0.999
12:122848039:C:A	S34R	0.999
12:122848039:C:G	S34R	0.999
12:122848047:A:T	K37I	0.999
12:122848049:G:C	A38P	0.999
12:122848050:C:A	A38D	0.999
12:122848076:A:G	K47E	0.999
12:122848078:G:C	K47N	0.999
12:122848078:G:T	K47N	0.999
12:122848082:A:G	K49E	0.999
12:122848477:G:C	G57R	0.999
12:122848478:G:A	G57D	0.999
12:122848481:C:A	T58K	0.999
12:122848481:C:G	T58R	0.999
12:122848510:T:A	W68R	0.999
12:122848510:T:C	W68R	0.999
12:122848584:G:C	K92N	0.999
12:122848584:G:T	K92N	0.999
12:122848597:G:T	G97W	0.999
12:122848598:G:A	G97E	0.999
12:122851237:T:C	F173L	0.999
12:122851239:C:A	F173L	0.999
12:122851239:C:G	F173L	0.999
12:122854923:T:C	L246P	0.999

dbSNP variants (sampled 300 via entrez): RS1000064558 (12:122846408 C>A,G), RS1000136784 (12:122840964 C>A), RS1000152168 (12:122833482 A>G), RS1000170535 (12:122846876 A>G), RS1000186240 (12:122839008 G>A,T), RS1000221583 (12:122846641 G>A), RS1000325961 (12:122849164 T>G), RS1000342421 (12:122835044 G>A), RS1000485485 (12:122834951 T>A,G), RS1000505233 (12:122845714 C>T), RS1000558166 (12:122842459 C>T), RS1000573381 (12:122836170 A>G), RS1000634402 (12:122841224 G>C), RS1000679586 (12:122833436 A>G), RS1000855602 (12:122841804 G>A)

Disease associations

OMIM: gene MIM:605613 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

34 associations (top):

Study	Trait	p-value
GCST000959_10	Parkinson’s disease	3.000000e-13
GCST006061_114	Atrial fibrillation	4.000000e-07
GCST006414_15	Atrial fibrillation	3.000000e-08
GCST007201_41	Schizophrenia	6.000000e-07
GCST007277_17	Tourette syndrome	2.000000e-06
GCST008128_4	Body mass index	8.000000e-15
GCST008129_66	Body mass index	2.000000e-14
GCST009325_11	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	1.000000e-37
GCST90002395_148	Mean platelet volume	3.000000e-10
GCST90020024_430	A body shape index	4.000000e-10
GCST90020024_432	A body shape index	3.000000e-15
GCST90020024_433	A body shape index	3.000000e-30
GCST90020024_434	A body shape index	6.000000e-17
GCST90020025_45	Waist-to-hip ratio adjusted for BMI	2.000000e-16
GCST90020025_46	Waist-to-hip ratio adjusted for BMI	2.000000e-19
GCST90020025_47	Waist-to-hip ratio adjusted for BMI	2.000000e-10
GCST90020025_48	Waist-to-hip ratio adjusted for BMI	9.000000e-25
GCST90020025_49	Waist-to-hip ratio adjusted for BMI	1.000000e-43
GCST90020025_50	Waist-to-hip ratio adjusted for BMI	3.000000e-23
GCST90020026_35	Hip index	4.000000e-09
GCST90020026_36	Hip index	2.000000e-10
GCST90020027_1247	Waist-hip index	7.000000e-17
GCST90020027_1249	Waist-hip index	9.000000e-11
GCST90020027_1250	Waist-hip index	2.000000e-24
GCST90020027_1251	Waist-hip index	9.000000e-43
GCST90020027_1252	Waist-hip index	1.000000e-22
GCST90020028_1253	Hip circumference adjusted for BMI	7.000000e-09
GCST90020028_1255	Hip circumference adjusted for BMI	5.000000e-10
GCST90020028_1256	Hip circumference adjusted for BMI	2.000000e-15
GCST90020028_1257	Hip circumference adjusted for BMI	2.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment	2
bisphenol F	affects cotreatment, decreases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
decabromobiphenyl ether	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
cupric chloride	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Arsenic Trioxide	decreases response to substance	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Atrazine	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	increases expression	1
Furaldehyde	affects cotreatment, affects localization, increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_DX04	HAP1 HIP1R (-) 1	Cancer cell line	Male
CVCL_DX05	HAP1 HIP1R (-) 2	Cancer cell line	Male
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

Clinical trials (associated diseases)

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