CEP19

Chr 3AR

centrosomal protein 19

Also known as: C3orf34, MOSPGF

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).

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

?Morbid obesity and spermatogenic failureMIM #615703
AR
1
Active trials
2
Pubs (1 yr)
89
P/LP submissions
0%
P/LP missense
1.09
LOEUF
DN
Mechanism· predicted
Clinical SummaryCEP19
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
88 unique Pathogenic / Likely Pathogenic· 94 VUS of 224 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.09LOEUF
pLI 0.016
Z-score 1.40
OE 0.48 (0.231.09)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.14Z-score
OE missense 1.04 (0.881.24)
94 obs / 90.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.48 (0.231.09)
00.351.4
Missense OE1.04 (0.881.24)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 4 / 8.4Missense obs/exp: 94 / 90.4Syn Z: 0.09
DN
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.

ClinVar Variant Classifications

224 submitted variants in ClinVar

Classification Summary

Pathogenic85
Likely Pathogenic3
VUS94
Likely Benign30
Benign5
Conflicting3
85
Pathogenic
3
Likely Pathogenic
94
VUS
30
Likely Benign
5
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
85
0
85
Likely Pathogenic
0
0
3
0
3
VUS
5
66
23
0
94
Likely Benign
0
0
6
24
30
Benign
0
1
2
2
5
Conflicting
3
Total56711926220

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

View in ClinVar →

Protein Context — Lollipop Plot

CEP19 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
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