HIP1

Chr 7

huntingtin interacting protein 1

Also known as: HIP-I, ILWEQ, SHON, SHONbeta, SHONgamma

NCBI Gene: 3092ENSG00000127946UniProt: O00291

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]

0
Active trials
26
Pathogenic / LP
166
ClinVar variants
16
Pubs (1 yr)
2.3
Missense Z
0.33
LOEUF· LoF intolerant
Clinical Summary— HIP1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.76) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 97 VUS of 166 total submissions
Some data sources returned errors (1)

pubtator: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.33LOEUF
pLI 0.762
Z-score 5.96
OE 0.21 (0.14–0.33)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.27Z-score
OE missense 0.74 (0.68–0.80)
439 obs / 594.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.21 (0.14–0.33)
0≤0.351.4
Missense OE0.74 (0.68–0.80)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 14 / 66.4Missense obs/exp: 439 / 594.5Syn Z: 1.03

ClinVar Variant Classifications

166 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic4
VUS97
Likely Benign24
Benign18
Conflicting1
22
Pathogenic
4
Likely Pathogenic
97
VUS
24
Likely Benign
18
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
4
0
4
VUS
0
80
17
0
97
Likely Benign
0
2
4
18
24
Benign
0
7
4
7
18
Conflicting
—1
Total0895125166

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

HIP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
NSUN2-mediated RNA m5C modification drives multiple myeloma progression by enhancing the stability of HIP1 mRNA.
Jiang Y et al.·Sci Rep
2025Open Access
Identification and functional characterization of hub genes CLTA, EDIL3, HAPLN1, and HIP1 as diagnostic biomarkers and therapeutic targets in thyroid cancer and Hashimoto's thyroiditis.
Liu T et al.·Clin Exp Med
2025Open AccessFunctional
Successful treatment of a non-small-cell lung cancer patient harboring HIP1-ALK (H28:A20) and CTNNB1 p.S45del with alectinib.
Longo V et al.·Thorac Cancer
2024Open Access
Targeted inhibition of NRF2 reduces the invasive and metastatic ability of HIP1 depleted lung cancer cells.
Prasad P et al.·Biochem Biophys Res Commun
2024
Y-box protein-1 modulates circSPECC1 to promote glioma tumorigenesis via miR-615-5p/HIP1/AKT axis.
Lan P et al.·Acta Biochim Biophys Sin (Shanghai)
2023Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients