CNTRL

Chr 9

centriolin

Also known as: CEP1, CEP110, FAN, bA165P4.1

This gene encodes a centrosomal protein that functions as a microtubule organizing center and anchors exocyst and SNARE complexes at the midbody during cytokinesis for proper cell division. The extremely low pLI score indicates this gene is highly tolerant to loss-of-function mutations, and no pediatric neurological diseases have been definitively associated with pathogenic variants in this gene. While chromosomal translocations involving this locus have been reported in hematologic malignancies, these do not represent typical Mendelian inheritance patterns relevant to pediatric neurology practice.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.89
Clinical SummaryCNTRL
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 unique Pathogenic / Likely Pathogenic· 279 VUS of 390 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.89LOEUF
pLI 0.000
Z-score 2.62
OE 0.76 (0.640.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.22Z-score
OE missense 0.98 (0.931.03)
1113 obs / 1133.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.76 (0.640.89)
00.351.4
Missense OE0.98 (0.931.03)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 102 / 134.8Missense obs/exp: 1113 / 1133.7Syn Z: 0.84
DN
0.6551th %ile
GOF
0.6442th %ile
LOF
0.3841th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

390 submitted variants in ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic1
VUS279
Likely Benign31
Benign9
Conflicting1
24
Pathogenic
1
Likely Pathogenic
279
VUS
31
Likely Benign
9
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
1
0
1
VUS
0
276
3
0
279
Likely Benign
0
28
0
3
31
Benign
0
5
0
4
9
Conflicting
1
Total0309287345

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

View in ClinVar →

Protein Context — Lollipop Plot

CNTRL · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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