CDC42EP1

Chr 22

CDC42 effector protein 1

Also known as: BORG5, CEP1, MSE55

The encoded protein binds CDC42 and mediates actin cytoskeleton reorganization at the plasma membrane, inducing membrane extensions in fibroblasts. Mutations cause autosomal recessive developmental delay with seizures and dysmorphic facial features. The gene shows tolerance to loss-of-function variants (low constraint), which is consistent with the recessive inheritance pattern observed in affected individuals.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 1.73
Clinical SummaryCDC42EP1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 unique Pathogenic / Likely Pathogenic· 84 VUS of 120 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.73LOEUF
pLI 0.000
Z-score 0.05
OE 0.98 (0.551.73)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.79Z-score
OE missense 1.14 (1.031.26)
272 obs / 237.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.98 (0.551.73)
00.351.4
Missense OE1.14 (1.031.26)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 7 / 7.1Missense obs/exp: 272 / 237.7Syn Z: -0.97
DN
0.5868th %ile
GOF
0.73top 25%
LOF
0.53top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

120 submitted variants in ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic1
VUS84
Likely Benign5
Benign5
Conflicting1
18
Pathogenic
1
Likely Pathogenic
84
VUS
5
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
1
0
1
VUS
0
80
4
0
84
Likely Benign
0
4
0
1
5
Benign
0
0
0
5
5
Conflicting
1
Total084236114

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

View in ClinVar →

Protein Context — Lollipop Plot

CDC42EP1 · 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.

Search ClinicalTrials.gov →
Clinical Literature
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