KIAA0753
Chr 17ARKIAA0753
Also known as: JBTS38, MNR, OFIP, SRTD21
The protein regulates centriole duplication and promotes centrosomal localization of key cell cycle proteins, and may function in cilium assembly. Mutations cause autosomal recessive ciliopathies including Joubert syndrome 38, orofaciodigital syndrome XV, and short-rib thoracic dysplasia 21 without polydactyly. The gene shows minimal constraint against loss-of-function variants (LOEUF 1.105), consistent with its recessive inheritance pattern.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-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.
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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 18 | 1 | 5 | 0 | 24 |
Likely Pathogenic | 15 | 1 | 0 | 0 | 16 |
VUS | 1 | 238 | 11 | 2 | 252 |
Likely Benign | 0 | 5 | 69 | 87 | 161 |
Benign | 0 | 3 | 11 | 3 | 17 |
Conflicting | — | 11 | |||
| Total | 34 | 248 | 96 | 92 | 481 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KIAA0753 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools