CEP72

Chr 5

centrosomal protein 72

NCBI Gene: 55722 ENSG00000112877 UniProt: Q9P209 OMIM: 616475

CEP72 encodes a centrosomal protein that recruits key proteins to the centrosome and provides microtubule-nucleation activity essential for proper spindle formation and centriole duplication. Mutations cause autosomal recessive primary microcephaly and Seckel syndrome, neurodevelopmental disorders characterized by severe intellectual disability, growth retardation, and distinctive facial features with prenatal or early postnatal onset. The gene shows very low constraint against loss-of-function variants, consistent with recessive inheritance patterns.

OMIM ResearchSummary from RefSeq, UniProt

The product of this gene is a member of the leucine-rich-repeat (LRR) superfamily of proteins. The protein is localized to the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.35

Clinical Summary— CEP72

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.35LOEUF

pLI 0.000

Z-score 0.04

OE 0.99 (0.74–1.35)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.89Z-score

OE missense 1.13 (1.04–1.22)

432 obs / 382.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.99 (0.74–1.35)

0≤0.351.4

Missense OE?1.13 (1.04–1.22)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 29 / 29.2Missense obs/exp: 432 / 382.9Syn Z: -0.12

This gene — mechanism propensity

0.6261th %ile

GOF

0.6151th %ile

LOF

0.3941th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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.