CEP19

Chr 3AR

centrosomal protein 19

Also known as: C3orf34, MOSPGF

NCBI Gene: 84984 ENSG00000174007 UniProt: Q96LK0 OMIM: 615586

The protein localizes to centrosomes and primary cilia, where it recruits RABL2B GTPase to initiate ciliation and is required for the early steps of cilium assembly. Mutations cause morbid obesity and spermatogenic failure, inherited in an autosomal recessive pattern. The gene shows relatively low constraint to loss-of-function variants (pLI 0.016, LOEUF 1.09).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene localizes to centrosomes and primary cilia and co-localizes with a marker for the mother centriole. This gene resides in a region of human chromosome 3 that is linked to morbid obesity. A homozygous knockout of the orthologous gene in mouse resulted in mice with morbid obesity, hyperphagy, glucose intolerance, and insulin resistance. Mutations in this gene cause morbid obesity and spermatogenic failure (MOSPGF). This gene has a pseudogene on human chromosome 2. [provided by RefSeq, Apr 2014]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.091 OMIM phenotype

Clinical Summary— CEP19

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Population Constraint (gnomAD)

Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.09LOEUF

pLI 0.016

Z-score 1.40

OE 0.48 (0.23–1.09)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.14Z-score

OE missense 1.04 (0.88–1.24)

94 obs / 90.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.48 (0.23–1.09)

0≤0.351.4

Missense OE?1.04 (0.88–1.24)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 4 / 8.4Missense obs/exp: 94 / 90.4Syn Z: 0.09

This gene — mechanism propensity

0.7035th %ile

GOF

0.5071th %ile

LOF

0.3067th %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.