HOOK1

Chr 1

hook microtubule tethering protein 1

Also known as: HK1

NCBI Gene: 51361ENSG00000134709UniProt: Q9UJC3

This gene encodes a member of the hook family of coiled-coil proteins, which bind to microtubules and organelles through their N- and C-terminal domains, respectively. The encoded protein localizes to discrete punctuate subcellular structures, and interacts with several members of the Rab GTPase family involved in endocytosis. It is thought to link endocytic membrane trafficking to the microtubule cytoskeleton. Several alternatively spliced transcript variants have been identified, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

118
ClinVar variants
16
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HOOK1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 97 VUS of 118 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.62LOEUF
pLI 0.000
Z-score 3.66
OE 0.43 (0.31–0.62)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.85Z-score
OE missense 0.87 (0.80–0.96)
318 obs / 363.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.43 (0.31–0.62)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.80–0.96)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 21 / 48.5Missense obs/exp: 318 / 363.5Syn Z: 0.51

ClinVar Variant Classifications

118 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic2
VUS97
Likely Benign5
14
Pathogenic
2
Likely Pathogenic
97
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
94
3
0
97
Likely Benign
0
3
0
2
5
Benign
0
0
0
0
0
Total097192118

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
📖
GeneReview available — HOOK1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
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
HOOK1 Inhibits the Progression of Renal Cell Carcinoma via TGF-β and TNFSF13B/VEGF-A Axis.
Yin L et al.·Adv Sci (Weinh)
2023
Protein homeostasis maintained by HOOK1 levels promotes the tumorigenic and stemness properties of ovarian cancer cells through reticulum stress and autophagy.
Suárez-Martínez E et al.·J Exp Clin Cancer Res
2024
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
MeCP2 AT-Hook1 mutations in patients with intellectual disability and/or schizophrenia disrupt DNA binding and chromatin compaction in vitro.
Sheikh TI et al.·Hum Mutat
2018Cohort
The Hook1 gene is non-functional in the abnormal spermatozoon head shape (azh) mutant mouse.
Mendoza-Lujambio I et al.·Hum Mol Genet
2002Functional
Clinical, Molecular, and Computational Analysis in Patients With a Novel Double Mutation and a New Synonymous Variant in MeCP2: Report of the First Missense Mutation Within the AT-hook1 Cluster in Rett Syndrome.
Kharrat M et al.·J Child Neurol
2017Cohort
Beyond Acephalic Spermatozoa: The Complexity of Intracytoplasmic Sperm Injection Outcomes.
Nie H et al.·Biomed Res Int
2020Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools