TMTC3

Chr 12

transmembrane O-mannosyltransferase targeting cadherins 3

Also known as: LIS8, SMILE

NCBI Gene: 160418 ENSG00000139324 UniProt: Q6ZXV5

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that belongs to the transmembrane and tetratricopeptide repeat-containing protein family. [provided by RefSeq, May 2010]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLissencephaly 8

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.56

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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