DOCK9

Chr 13

dedicator of cytokinesis 9

Also known as: ZIZ1, ZIZIMIN1

This protein functions as a guanine nucleotide-exchange factor that activates CDC42 and induces filopodia formation, playing a role in cellular signaling and cytoskeletal organization. Mutations cause intellectual disability and developmental delay with variable additional features including seizures, behavioral abnormalities, and dysmorphic features, following an autosomal dominant inheritance pattern. The gene is highly constrained against loss-of-function variants, indicating intolerance to protein-disrupting mutations.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
91
P/LP submissions
0%
P/LP missense
0.19
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryDOCK9
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.
📋
ClinVar Variants
91 unique Pathogenic / Likely Pathogenic· 231 VUS of 404 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.19LOEUF
pLI 1.000
Z-score 8.70
OE 0.12 (0.080.19)
Highly constrained

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

Missense Constraint
3.10Z-score
OE missense 0.74 (0.700.78)
821 obs / 1111.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.12 (0.080.19)
00.351.4
Missense OE0.74 (0.700.78)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 14 / 114.3Missense obs/exp: 821 / 1111.7Syn Z: 0.13
DN
0.3793th %ile
GOF
0.4481th %ile
LOF
0.67top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.19

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

404 submitted variants in ClinVar

Classification Summary

Pathogenic89
Likely Pathogenic2
VUS231
Likely Benign12
Benign4
Conflicting1
89
Pathogenic
2
Likely Pathogenic
231
VUS
12
Likely Benign
4
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
89
0
89
Likely Pathogenic
0
0
2
0
2
VUS
0
227
4
0
231
Likely Benign
0
2
1
9
12
Benign
0
1
0
3
4
Conflicting
1
Total02309612339

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

View in ClinVar →

Protein Context — Lollipop Plot

DOCK9 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →