HIP1

huntingtin interacting protein 1

Basic information

Region (hg38): 7:75533297-75738962

Links

ENSG00000127946 ∙ NCBI:3092 ∙ OMIM:601767 ∙ HGNC:4913 ∙ Uniprot:O00291 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HIP1 gene.

• Inborn genetic diseases (37 variants)
• not provided (34 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HIP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				13	3	16
missense			41	2	6	49
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	2	3
non coding				2	1	3
Total	0	0	41	17	10

Variants in HIP1

This is a list of pathogenic ClinVar variants found in the HIP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-75539347-C-T			Uncertain significance (May 01, 2018)
7-75539348-A-G		HIP1-related disorder	Likely benign (Aug 14, 2019)
7-75539357-G-A		HIP1-related disorder	Likely benign (Mar 25, 2019)
7-75539392-G-A		not specified	Uncertain significance (Sep 29, 2022)
7-75541938-C-T		not specified	Uncertain significance (Jun 21, 2022)
7-75541939-G-A		not specified	Uncertain significance (Apr 12, 2023)
7-75541945-T-C		not specified	Uncertain significance (Apr 07, 2022)
7-75541956-G-A		not specified	Uncertain significance (Sep 15, 2021)
7-75542860-C-T		not specified	Uncertain significance (Aug 02, 2021)
7-75542876-G-A			Likely benign (Oct 17, 2018)
7-75542880-A-G		not specified	Uncertain significance (Feb 13, 2024)
7-75542883-G-C		not specified	Uncertain significance (May 24, 2023)
7-75542899-C-T		not specified	Uncertain significance (Jan 24, 2023)
7-75542923-G-A		not specified	Uncertain significance (Apr 18, 2023)
7-75542934-T-C			Benign (Dec 31, 2019)
7-75542943-G-T		not specified	Uncertain significance (Oct 30, 2023)
7-75542951-G-A		HIP1-related disorder	Benign (Nov 05, 2019)
7-75544729-G-T			Uncertain significance (Feb 01, 2018)
7-75544737-A-T		not specified	Uncertain significance (Jul 12, 2023)
7-75544751-T-G		not specified	Uncertain significance (Oct 04, 2022)
7-75544792-G-A		not specified	Uncertain significance (Aug 02, 2021)
7-75545108-G-C			Likely benign (Mar 29, 2018)
7-75546932-C-T		HIP1-related disorder	Likely benign (Dec 30, 2019)
7-75546944-C-T		not specified	Uncertain significance (Feb 07, 2023)
7-75546945-G-T		not specified	Uncertain significance (Mar 05, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HIP1	protein_coding	protein_coding	ENST00000336926	31	205660

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.762	0.238	125720	0	28	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.27	439	594	0.738	0.0000337	6792
Missense in Polyphen		114	179.95	0.63352		2046
Synonymous	1.03	223	243	0.916	0.0000150	1983
Loss of Function	5.96	14	66.4	0.211	0.00000362	713

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000206	0.000206
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000179	0.000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in clathrin-mediated endocytosis and trafficking (PubMed:11532990, PubMed:11577110, PubMed:11889126). Involved in regulating AMPA receptor trafficking in the central nervous system in an NMDA-dependent manner (By similarity). Regulates presynaptic nerve terminal activity (By similarity). Enhances androgen receptor (AR)-mediated transcription (PubMed:16027218). May act as a proapoptotic protein that induces cell death by acting through the intrinsic apoptosis pathway (PubMed:11007801). Binds 3-phosphoinositides (via ENTH domain) (PubMed:14732715). May act through the ENTH domain to promote cell survival by stabilizing receptor tyrosine kinases following ligand-induced endocytosis (PubMed:14732715). May play a functional role in the cell filament networks (PubMed:18790740). May be required for differentiation, proliferation, and/or survival of somatic and germline progenitors (PubMed:11007801, PubMed:12163454). {ECO:0000250|UniProtKB:Q8VD75, ECO:0000269|PubMed:11007801, ECO:0000269|PubMed:11532990, ECO:0000269|PubMed:11577110, ECO:0000269|PubMed:11889126, ECO:0000269|PubMed:12163454, ECO:0000269|PubMed:14732715, ECO:0000269|PubMed:16027218, ECO:0000269|PubMed:18790740, ECO:0000269|PubMed:9147654}.
• Disease: DISEASE: Note=A chromosomal aberration involving HIP1 is found in a form of chronic myelomonocytic leukemia (CMML). Translocation t(5;7)(q33;q11.2) with PDGFRB (PubMed:9616134). The chimeric HIP1- PDGFRB transcript results from an in-frame fusion of the two genes (PubMed:9616134). The reciprocal PDGFRB-HIP1 transcript is not expressed (PubMed:9616134). {ECO:0000269|PubMed:9616134}.
• Pathway: Huntington,s disease - Homo sapiens (human);Vesicle-mediated transport;Membrane Trafficking;Clathrin-mediated endocytosis;EGFR1;Coregulation of Androgen receptor activity (Consensus)

Recessive Scores

• pRec: 0.304

Intolerance Scores

• loftool: 0.313
• rvis_EVS: -0.99
• rvis_percentile_EVS: 8.6

Haploinsufficiency Scores

• pHI: 0.659
• hipred: Y
• hipred_score: 0.756
• ghis: 0.511

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.753

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hip1
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; muscle phenotype; immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype; respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); neoplasm; hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; vision/eye phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: hip1
• Affected structure: ventral mandibular arch
• Phenotype tag: abnormal
• Phenotype quality: aplastic

Gene ontology

• Biological process: apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;actin filament organization;regulation of endocytosis;cell differentiation;regulation of apoptotic process;positive regulation of epidermal growth factor receptor signaling pathway;positive regulation of receptor-mediated endocytosis;clathrin coat assembly;protein stabilization;positive regulation of protein kinase B signaling;membrane organization;clathrin-dependent endocytosis;apoptotic signaling pathway;neurotransmitter receptor transport;positive regulation of platelet-derived growth factor receptor-beta signaling pathway
• Cellular component: nucleus;cytoplasm;Golgi apparatus;cytosol;cytoskeleton;membrane;AP-2 adaptor complex;clathrin-coated vesicle;actin cortical patch;extrinsic component of cytoplasmic side of plasma membrane;intracellular membrane-bounded organelle;presynapse;postsynapse;extrinsic component of presynaptic membrane;extrinsic component of postsynaptic membrane;glutamatergic synapse
• Molecular function: epidermal growth factor receptor binding;structural constituent of cytoskeleton;protein binding;phosphatidylinositol-4,5-bisphosphate binding;clathrin binding;clathrin light chain binding;phosphatidylinositol-3-phosphate binding;phosphatidylinositol binding;glutamate receptor binding;AP-2 adaptor complex binding;clathrin adaptor activity;protein homodimerization activity;phosphatidylinositol-3,4-bisphosphate binding;protein heterodimerization activity;actin filament binding;phosphatidylinositol-3,5-bisphosphate binding