KCTD1

Chr 18

potassium channel tetramerization domain containing 1

Also known as: C18orf5, DNRD, RMDA

NCBI Gene: 284252 ENSG00000134504 UniProt: Q719H9

The protein negatively regulates AP-2 transcription factors and the Wnt signaling pathway by enhancing ubiquitination and degradation of beta-catenin. Mutations cause scalp-ear-nipple syndrome and dental radicular dysplasia with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.86, LOEUF 0.44), indicating intolerance to protein-disrupting mutations.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein containing a BTB (Broad-complex, tramtrack and bric a brac), also known as a POZ (POxvirus and zinc finger) protein-protein interaction domain. The encoded protein negatively regulates the AP-2 family of transcription factors and the Wnt signaling pathway. A mechanism for the modulation of Wnt signaling has been proposed in which the encoded protein enhances ubiquitination and degradation of the beta-catenin protein. Mutations in this gene have been identified in Scalp-ear-nipple (SEN) syndrome. [provided by RefSeq, May 2017]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtScalp-ear-nipple syndrome

UniProtDental radicular dysplasia

Clinical highlights

Gene-disease validity (ClinGen)

scalp-ear-nipple syndrome · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.44

LOEUF

GOF*

Mechanism· G2P

Some data sources returned errors (1)

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