CDC42EP1

Chr 22

CDC42 effector protein 1

Also known as: BORG5, CEP1, MSE55

NCBI Gene: 11135 ENSG00000128283 UniProt: Q00587 OMIM: 606084

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.

OMIM ResearchSummary from RefSeq, UniProt

CDC42 is a member of the Rho GTPase family that regulates multiple cellular activities, including actin polymerization. The protein encoded by this gene is a CDC42 binding protein that mediates actin cytoskeleton reorganization at the plasma membrane. This protein is secreted and is primarily found in bone marrow. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.73

Clinical Summary— CDC42EP1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

80 VUS of 96 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.73LOEUF

pLI 0.000

Z-score 0.05

OE 0.98 (0.55–1.73)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.79Z-score

OE missense 1.14 (1.03–1.26)

272 obs / 237.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.98 (0.55–1.73)

0≤0.351.4

Missense OE?1.14 (1.03–1.26)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 7 / 7.1Missense obs/exp: 272 / 237.7Syn Z: -0.97

This gene — mechanism propensity

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

96 submitted variants in ClinVar

ClinVar

Classification Summary

VUS80

Likely Benign5

Benign5

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	80	0	80
Likely Benign	4	1	5
Benign	0	5	5
Total	84	6	90

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap CDC42EP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →