TMCO1

Chr 1

transmembrane and coiled-coil domains 1

Also known as: CFSMR1, HP10122, PCIA3, PNAS-136, TMCC4

NCBI Gene: 54499 ENSG00000143183 UniProt: Q9UM00

The TMCO1 protein functions as an endoplasmic reticulum calcium-selective channel that maintains ER calcium homeostasis and serves as a component of the multi-pass translocon complex for membrane protein insertion. Biallelic mutations cause craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development with autosomal recessive inheritance. This gene shows extremely strong constraint against loss-of-function variants (pLI ~1), indicating that heterozygous loss-of-function is likely incompatible with normal development.

GeneReviews ResearchSummary from OMIM, UniProt

This locus encodes a transmembrane protein. Mutations at this locus have been associated with craniofacial dysmorphism, skeletal anomalies, and cognitive disability. Mutations at this locus have also been associated with open angle glaucoma blindness. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2012]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCraniofacial dysmorphism, skeletal anomalies and impaired intellectual development syndrome 1

UniProtGlaucoma, primary open angle

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)

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P/LP submissions

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P/LP missense

1.36

LOEUF

LOF

Mechanism· G2P

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GeneReview available — TMCO1