CDC42EP2

Chr 11

CDC42 effector protein 2

Also known as: BORG1, CEP2

NCBI Gene: 10435 ENSG00000149798 UniProt: O14613 OMIM: 606132

CDC42EP2 encodes a member of the Borg family of CDC42 effector proteins that binds to and negatively regulates CDC42, inducing actin filament assembly and pseudopodia formation to control cell shape. Mutations cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in infancy or early childhood. The gene is not highly constrained to loss-of-function variation, consistent with the recessive inheritance pattern observed in affected individuals.

OMIM ResearchSummary from RefSeq, UniProt

CDC42, a small Rho GTPase, regulates the formation of F-actin-containing structures through its interaction with the downstream effector proteins. The protein encoded by this gene is a member of the Borg family of CDC42 effector proteins. Borg family proteins contain a CRIB (Cdc42/Rac interactive-binding) domain. They bind to, and negatively regulate the function of CDC42. Coexpression of this protein with CDC42 suggested a role of this protein in actin filament assembly and cell shape control. [provided by RefSeq, Aug 2011]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.77

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.77LOEUF

pLI 0.039

Z-score 0.45

OE 0.71 (0.28–1.77)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.52Z-score

OE missense 0.87 (0.75–1.02)

119 obs / 136.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.71 (0.28–1.77)

0≤0.351.4

Missense OE?0.87 (0.75–1.02)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 2 / 2.8Missense obs/exp: 119 / 136.2Syn Z: 0.82

Background carrier burden — how many people carry a rare variant somewhere in CDC42EP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

268 rare PASS variants

Rare truncating (LoF)

1 in 7,100

29 rare PASS variants

Rare synonymous (reference)

1 in 170

121 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CDC42EP2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 370	1 in 7,400
South Asian	~43k	1 in 160	1 in 8,600
Remaining (unassigned)	~30k	1 in 240	≈ 1 in 6,000
European (Finnish)	~27k	1 in 1,200	≈ 1 in 13,000
Admixed American	~22k	1 in 94	1 in 2,500
African / African American	~21k	1 in 130	≈ 1 in 17,000
East Asian	~20k	1 in 230	1 in 3,300
Ashkenazi Jewish	~13k	1 in 1,900	none seen
Middle Eastern	~2,884	1 in 140	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓