TMTC3
Chr 12ARtransmembrane O-mannosyltransferase targeting cadherins 3
Also known as: LIS8, SMILE
This protein functions as an O-mannosyl-transferase that transfers mannose residues to serine or threonine residues, primarily on cadherin superfamily proteins, and regulates proteasomal protein degradation in the endoplasmic reticulum. Mutations cause autosomal recessive lissencephaly 8, a severe brain malformation disorder affecting cortical development. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.56), consistent with its role in essential cellular glycosylation processes.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TMTC3 · 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