TULP3
Chr 12ARTUB like protein 3
Also known as: HRCDF, TUBL3
TULP3 encodes a negative regulator of Sonic hedgehog (Shh) signaling that controls trafficking of G protein-coupled receptors to primary cilia and binds phosphoinositide lipids. Mutations cause hepatorenocardiac degenerative fibrosis, a multisystem disorder affecting liver, kidney, and heart through autosomal recessive inheritance. The gene is extremely intolerant to loss-of-function variants (pLI near 1.0), indicating high evolutionary constraint.
Primary Disease Associations & Inheritance
Strong evidence — appropriate for clinical testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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
195 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 | 3 | 2 | 62 | 0 | 67 |
Likely Pathogenic | 2 | 0 | 3 | 0 | 5 |
VUS | 0 | 75 | 6 | 0 | 81 |
Likely Benign | 0 | 10 | 1 | 3 | 14 |
Benign | 0 | 2 | 1 | 0 | 3 |
Conflicting | — | 1 | |||
| Total | 5 | 89 | 73 | 3 | 171 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TULP3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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