TMEM165

Chr 4AR

transmembrane protein 165

Also known as: CDG2K, FT27, GDT1, SLC64A1, TMPT27, TPARL

NCBI Gene: 55858 ENSG00000134851 UniProt: Q9HC07 OMIM: 614726

This gene encodes a divalent cation:proton antiporter that exchanges calcium or manganese ions for protons across the Golgi membrane, providing essential cofactors to Golgi enzymes involved in glycosylation. Biallelic mutations cause congenital disorder of glycosylation type IIk, an autosomal recessive condition affecting protein glycosylation. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.63), suggesting some tolerance to reduced function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a predicted transmembrane protein with a perinuclear Golgi-like distribution in fibroblasts. Mutations in this gene are associated with the autosomal recessive disorder congenital disorder of glycosylation, type IIk. Knockdown of this gene's expression causes decreased sialylation in HEK cells and suggests this gene plays a role in terminal Golgi glycosylation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IIkMIM #614727

Clinical highlights

Gene-disease validity (ClinGen)

TMEM165-congenital disorder of glycosylation · ARModerateconsider for supplementary testing

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.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

0.63

LOEUF

LOF

Mechanism· G2P