HIP1

Chr 7

huntingtin interacting protein 1

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

The HIP1 protein functions in clathrin-mediated endocytosis and regulates AMPA receptor trafficking in the central nervous system. Pathogenic variants in HIP1 cause intellectual disability with seizures and characteristic dysmorphic features, inherited in an autosomal dominant pattern. The gene shows significant constraint against loss-of-function variants (LOEUF 0.33), indicating intolerance to protein loss.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.33
Clinical SummaryHIP1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.76) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 148 VUS of 268 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.33LOEUF
pLI 0.762
Z-score 5.96
OE 0.21 (0.140.33)
Highly constrained

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

Missense Constraint
2.27Z-score
OE missense 0.74 (0.680.80)
439 obs / 594.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.21 (0.140.33)
00.351.4
Missense OE0.74 (0.680.80)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 14 / 66.4Missense obs/exp: 439 / 594.5Syn Z: 1.03

ClinVar Variant Classifications

268 submitted variants in ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic4
VUS148
Likely Benign26
Benign18
Conflicting1
23
Pathogenic
4
Likely Pathogenic
148
VUS
26
Likely Benign
18
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
4
0
4
VUS
0
130
18
0
148
Likely Benign
0
3
5
18
26
Benign
0
7
4
7
18
Conflicting
1
Total01405425220

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

View in ClinVar →

Protein Context — Lollipop Plot

HIP1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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