GeneBe

HIP1

protein-coding

huntingtin interacting protein 1

Gene summary

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. [provided by RefSeq, Jul 2013]

MANE transcript

NM_005338.7

Inheritance

—

ClinVar variants

U:149B:36

Top phenotype

HIP1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr7:75,533,298-75,738,962

External References & Databases

Ensembl (ENSG00000127946)NCBI Gene (3092)OMIM (601767)HGNC:4913GenCCUniProt (O00291)AlphaFoldClinVar (HIP1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~205.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HIP1 variants in ClinVar

3 Conditions Cataloged
not specifiedTotal: 141
not providedTotal: 35
HIP1-related disorderTotal: 18

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005338.7. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
22
clinvar
3
clinvar
 26
missense
137
clinvar
4
clinvar
7
clinvar
 148
nonsense
0
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
10
clinvar
 10
Total001492610185
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_005338.7RefSeqNP_005329.331MANE Select
ENST00000336926.11EnsemblENSP00000336747.631MANE Select
NM_001243198.3RefSeqNP_001230127.129Standard
NM_001382444.1RefSeqNP_001369373.131Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
hip1Danio rerio

Structure: ventral mandibular arch

Quality: aplastic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Huntington,s disease - Homo sapiens (human)
  • Vesicle-mediated transport
  • Membrane Trafficking
  • Clathrin-mediated endocytosis
  • EGFR1

Biological Process

  • apoptotic process
  • activation of cysteine-type endopeptidase activity involved in apoptotic process
  • actin filament organization
  • regulation of endocytosis
  • cell differentiation

Molecular Function

  • epidermal growth factor receptor binding
  • structural constituent of cytoskeleton
  • protein binding
  • phosphatidylinositol-4,5-bisphosphate binding
  • clathrin binding

Cellular Component

  • nucleus
  • cytoplasm
  • Golgi apparatus
  • cytosol
  • cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000336926
Coding exons
31
Length
205660
Individuals with no LoFs
125720
Homozygous LoFs
0
Heterozygous LoFs
28
Defined
125748
p
0.000111
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.274395940.7380.00003376792
Missense (PolyPhen)114179.950.633522046
Synonymous1.032232430.9160.00001501983
Loss of Function5.961466.40.2110.00000362713

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.000140.00012rare
Ashkenazi Jewish00.0absent
East Asian0.0000540.000054rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.000180.00018rare
South Asian0.0000330.000033rare
Other00.0absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec
0.304

Intolerance Scores

LoFtool
0.313
RVIS EVS
-0.99
RVIS percentile EVS
8.6

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.753

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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