CEP152

Chr 15AR

centrosomal protein 152

Also known as: MCPH4, MCPH9, SCKL5

NCBI Gene: 22995 ENSG00000103995 UniProt: O94986 OMIM: 613529

The protein localizes to the centrosome and functions in centrosome biogenesis and microtubule organization. Mutations cause primary microcephaly (MCPH4) and Seckel syndrome 5 through autosomal recessive inheritance. The pathogenic mechanism involves disrupted centrosome function leading to abnormal cell division and impaired brain development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that is thought to be involved with centrosome function. Mutations in this gene have been associated with primary microcephaly (MCPH4). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.822 OMIM phenotypes

Clinical Summary— CEP152

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Gene-Disease Validity (ClinGen)

microcephaly with or without short stature · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

120 unique Pathogenic / Likely Pathogenic· 320 VUS of 1066 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — CEP152

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.000

Z-score 2.91

OE 0.66 (0.53–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.03Z-score

OE missense 1.00 (0.94–1.06)

831 obs / 833.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.66 (0.53–0.82)

0≤0.351.4

Missense OE?1.00 (0.94–1.06)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 56 / 85.0Missense obs/exp: 831 / 833.3Syn Z: -0.33

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCEP152-related developmental disorderLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6550th %ile

GOF

0.5758th %ile

LOF

0.3647th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

1066 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic75

Likely Pathogenic45

VUS320

Likely Benign493

Benign59

Conflicting62

Pathogenic

Likely Pathogenic

320

VUS

493

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	72	1	2	0	75
Likely Pathogenic	43	2	0	0	45
VUS	7	287	22	4	320
Likely Benign	9	15	192	277	493
Benign	0	5	51	3	59
Conflicting	—				62
Total	131	310	267	284	1,054

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap CEP152 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →