HOOK2

Chr 19

hook microtubule tethering protein 2

Also known as: HK2

NCBI Gene: 29911ENSG00000095066UniProt: Q96ED9

Hook proteins are cytosolic coiled-coil proteins that contain conserved N-terminal domains, which attach to microtubules, and more divergent C-terminal domains, which mediate binding to organelles. The Drosophila Hook protein is a component of the endocytic compartment.[supplied by OMIM, Apr 2004]

180
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HOOK2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 153 VUS of 180 total submissions
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?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.
0.93LOEUF
pLI 0.000
Z-score 1.98
OE 0.70 (0.53–0.93)
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.
0.37Z-score
OE missense 0.95 (0.88–1.03)
429 obs / 451.2 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.0.70 (0.53–0.93)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.88–1.03)
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.0.93
0≤1.21.6
LoF obs/exp: 35 / 50.2Missense obs/exp: 429 / 451.2Syn Z: 0.79

ClinVar Variant Classifications

180 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic2
VUS153
Likely Benign5
Benign2
Conflicting1
17
Pathogenic
2
Likely Pathogenic
153
VUS
5
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
2
0
2
VUS
0
148
5
0
153
Likely Benign
0
4
0
1
5
Benign
0
1
1
0
2
Conflicting
—1
Total0153251180

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

View in ClinVar →

Protein Context — Lollipop Plot

HOOK2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Coding Variants in HOOK2 and GTPBP3 May Contribute to Risk of Primary Angle Closure Glaucoma.
Qiao C et al.·DNA Cell Biol
2020
Sexually dimorphic DNA-methylation in cardiometabolic health: A systematic review.
Asllanaj E et al.·Maturitas
2020Review
Investigation of Novel Predictive Biomarkers for Preeclampsia in Second-Trimester Amniotic Fluid.
Lee HE et al.·Int J Mol Sci
2025
SUT-2 potentiates tau-induced neurotoxicity in Caenorhabditis elegans.
Guthrie CR et al.·Hum Mol Genet
2009
Hook proteins: association with Alzheimer pathology and regulatory role of hook3 in amyloid beta generation.
Herrmann L et al.·PLoS One
2015
Epigenetic association analysis of clinical sub-phenotypes in patients with polycystic ovary syndrome (PCOS).
Jacobsen VM et al.·Gynecol Endocrinol
2019Cohort
Long non-coding RNA HIF1A-AS2 modulates the proliferation, migration, and phenotypic switch of aortic smooth muscle cells in aortic dissection via sponging microRNA-33b.
Zhang K et al.·Bioengineered
2022
An FTS/Hook/p107(FHIP) complex interacts with and promotes endosomal clustering by the homotypic vacuolar protein sorting complex.
Xu L et al.·Mol Biol Cell
2008
Mutations in known disease genes account for the majority of autosomal recessive retinal dystrophies.
Patel N et al.·Clin Genet
2018
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