HIP1R
protein-codinghuntingtin interacting protein 1 related
Gene summary
Enables several functions, including actin filament binding activity; anion binding activity; and protein homodimerization activity. Involved in several processes, including positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; positive regulation of signal transduction; and protein stabilization. Located in clathrin-coated vesicle; cytosol; and ruffle membrane. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~28.5 kbGenCC 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 HIP1R variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003959.3. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 1 | 3 | ||
| missense | 193 | 9 | 1 | 203 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 200 | 10 | 2 | 212 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003950.1 | 32 | MANE Select | |
| Ensembl | ENSP00000253083.4 | 32 | MANE Select | |
| RefSeq | NP_001290026.1 | 18 | Standard | |
| RefSeq | NP_001290028.1 | 18 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Golgi Associated Vesicle Biogenesis
- Clathrin derived vesicle budding
- trans-Golgi Network Vesicle Budding
- Vesicle-mediated transport
- Membrane Trafficking
Biological Process
- receptor-mediated endocytosis
- apoptotic process
- activation of cysteine-type endopeptidase activity involved in apoptotic process
- actin filament organization
- regulation of endocytosis
Molecular Function
- protein binding
- phosphatidylinositol-4,5-bisphosphate binding
- phosphatidylinositol-3,4,5-trisphosphate binding
- SH3 domain binding
- clathrin binding
Cellular Component
- cytoplasm
- mitochondrion
- cytosol
- postsynaptic density
- apical plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000253083
- Coding exons
- 32
- Length
- 28508
- Individuals with no LoFs
- 125645
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 101
- Defined
- 125746
- p
- 0.000402
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0290 | 656 | 654 | 1.00 | 0.0000433 | 6871 |
| Missense (PolyPhen) | 200 | 227.55 | 0.87894 | 2429 | ||
| Synonymous | -1.12 | 315 | 291 | 1.08 | 0.0000204 | 2112 |
| Loss of Function | 3.12 | 34 | 60.1 | 0.565 | 0.00000293 | 689 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00030 | 0.00029 | rare |
| Ashkenazi Jewish | 0.0011 | 0.0011 | notable |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00036 | 0.00032 | rare |
| European (Non-Finnish) | 0.00046 | 0.00046 | rare |
| South Asian | 0.00050 | 0.00039 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- 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. {ECO:0000269|PubMed:11889126, ECO:0000269|PubMed:14732715}.;
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- LoFtool
- 0.803
- RVIS EVS
- -1.05
- RVIS percentile EVS
- 7.6
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.753
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |