HOOK3

Chr 8

hook microtubule tethering protein 3

Also known as: HK3

HOOK3 encodes an adapter protein that links the dynein motor complex to cellular cargos and activates dynein processivity for microtubule-based transport, while also participating in vesicle trafficking and Golgi complex organization. Mutations cause autosomal recessive progressive familial intrahepatic cholestasis with neurologic features including intellectual disability and cerebellar atrophy. This gene is highly constrained against loss-of-function variants, indicating that functional HOOK3 protein is essential for normal cellular function.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.15
Clinical SummaryHOOK3
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.15LOEUF
pLI 1.000
Z-score 6.16
OE 0.06 (0.030.15)
Highly constrained

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

Missense Constraint
2.36Z-score
OE missense 0.65 (0.580.72)
230 obs / 354.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.06 (0.030.15)
00.351.4
Missense OE0.65 (0.580.72)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 3 / 50.0Missense obs/exp: 230 / 354.9Syn Z: 1.04

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HOOK3 · 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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