TMEM67
Chr 8ARtransmembrane protein 67
Also known as: JBTS6, MECKELIN, MKS3, NPHP11, TNEM67
The protein localizes to the primary cilium and plasma membrane where it regulates ciliary structure, function, and length, controls centrosome migration and duplication, and participates in Wnt signaling pathways. Autosomal recessive mutations cause a spectrum of ciliopathies including Meckel syndrome type 3, Joubert syndrome type 6, COACH syndrome, and nephronophthisis 11, likely through loss of normal ciliary function. The protein is also associated with RHYNS syndrome and acts as a modifier in Bardet-Biedl syndrome.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
200 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 | 12 | 1 | 5 | 0 | 18 |
Likely Pathogenic | 14 | 5 | 0 | 0 | 19 |
VUS | 2 | 72 | 6 | 1 | 81 |
Likely Benign | 0 | 1 | 19 | 23 | 43 |
Benign | 0 | 0 | 3 | 0 | 3 |
Conflicting | — | 1 | |||
| Total | 28 | 79 | 33 | 24 | 165 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TMEM67 · 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
External Resources
Links to major genomics databases and tools