DOCK10

Chr 2

dedicator of cytokinesis 10

Also known as: DRIP2, Nbla10300, ZIZ3

The protein functions as a guanine nucleotide-exchange factor that activates CDC42 and RAC1 GTPases and is essential for dendritic spine morphogenesis in Purkinje cells and hippocampal neurons. Mutations cause autosomal recessive intellectual disability with seizures, microcephaly, and cerebellar atrophy. The gene is highly constrained against loss-of-function variants, indicating that complete protein loss is likely incompatible with normal development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
7
Pubs (1 yr)
27
P/LP submissions
0%
P/LP missense
0.39
LOEUF
Mechanism
Clinical SummaryDOCK10
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 266 VUS of 352 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.000
Z-score 7.11
OE 0.29 (0.220.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.88Z-score
OE missense 0.84 (0.800.89)
922 obs / 1097.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.29 (0.220.39)
00.351.4
Missense OE0.84 (0.800.89)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 34 / 117.0Missense obs/exp: 922 / 1097.2Syn Z: 1.31

ClinVar Variant Classifications

352 submitted variants in ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic1
VUS266
Likely Benign9
Benign5
Conflicting1
26
Pathogenic
1
Likely Pathogenic
266
VUS
9
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
1
0
1
VUS
0
264
2
0
266
Likely Benign
0
8
0
1
9
Benign
0
1
1
3
5
Conflicting
1
Total0273304308

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

View in ClinVar →

Protein Context — Lollipop Plot

DOCK10 · protein map & ClinVar variants

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

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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