HOOK1

Chr 1

hook microtubule tethering protein 1

Also known as: HK1

NCBI Gene: 51361ENSG00000134709UniProt: Q9UJC3

The HOOK1 protein is a component of the FTS/Hook/FHIP complex that promotes vesicle trafficking and fusion by linking endocytic membrane trafficking to the microtubule cytoskeleton. Mutations cause autosomal recessive spermatogenic failure, leading to male infertility due to defects in spermatid differentiation and flagellar positioning. The gene is not highly constrained against loss-of-function variants, consistent with its specialized role in male reproductive function.

GeneReviewsResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.62
Clinical Summary— HOOK1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 98 VUS of 142 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — HOOK1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.62LOEUF
pLI 0.000
Z-score 3.66
OE 0.43 (0.31–0.62)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.85Z-score
OE missense 0.87 (0.80–0.96)
318 obs / 363.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.43 (0.31–0.62)
0≤0.351.4
Missense OE0.87 (0.80–0.96)
0≤0.61.4
Synonymous OE0.94
0≤1.21.6
LoF obs/exp: 21 / 48.5Missense obs/exp: 318 / 363.5Syn Z: 0.51
DN
0.7326th %ile
GOF
0.5955th %ile
LOF
0.3260th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

142 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic2
VUS98
Likely Benign5
14
Pathogenic
2
Likely Pathogenic
98
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
2
0
2
VUS
0
95
3
0
98
Likely Benign
0
3
0
2
5
Benign
0
0
0
0
0
Total098192119

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

View in ClinVar →

Protein Context — Lollipop Plot

HOOK1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF-β and TNFSF13B/VEGF-A Axis.
Yin L et al.·Adv Sci (Weinh)
2023
Analysis of multiple programmed cell death-related prognostic genes and functional validations of necroptosis-associated genes in oesophageal squamous cell carcinoma.
Cao K et al.·EBioMedicine
2024Functional
Clinicopathological and prognostic significance of SHP2 and Hook1 expression in patients with thyroid carcinoma.
Cao J et al.·Hum Pathol
2018Cohort
The clinicopathological and prognostic implications of tyrosine phosphatase SHP2 and ankyrin Hook1 gene expression in non- small cell lung cancer patients treated with gemcitabine plus platinum as first-line chemotherapy.
Yang H et al.·Ann Palliat Med
2020Cohort
HOOK1 Gene Expression and DNA Methylation in Obesity and Related Cardiometabolic Traits.
Svensson SIA et al.·Obes Facts
2026
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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