CEP170

Chr 1

centrosomal protein 170

Also known as: FAM68A, KAB, KIAA0470

NCBI Gene: 9859 ENSG00000143702 UniProt: Q5SW79 OMIM: 613023

CEP170 encodes a centrosomal protein required for centriole subdistal appendage assembly and microtubule organization during both interphase and mitosis. Mutations cause autosomal recessive primary microcephaly with seizures and intellectual disability, reflecting the gene's critical role in proper cell division and brain development. This gene is highly constrained against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

The product of this gene is a component of the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. During interphase, the encoded protein localizes to the sub-distal appendages of mature centrioles, which are microtubule-based structures thought to help organize centrosomes. During mitosis, the protein associates with spindle microtubules near the centrosomes. The protein interacts with and is phosphorylated by polo-like kinase 1, and functions in maintaining microtubule organization and cell morphology. The human genome contains a putative transcribed pseudogene. Several alternatively spliced transcript variants of this gene have been found, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.19

Clinical Summary— CEP170

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 1.000

Z-score 6.58

OE 0.10 (0.05–0.19)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.20Z-score

OE missense 0.78 (0.72–0.83)

593 obs / 763.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.10 (0.05–0.19)

0≤0.351.4

Missense OE?0.78 (0.72–0.83)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 6 / 61.8Missense obs/exp: 593 / 763.9Syn Z: 1.92

This gene — mechanism propensity

0.3892th %ile

GOF

0.4381th %ile

LOF

0.79top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.19

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.