Paediatric disorders - additional genes

Gene: KCTD15

I don't know

Comment on list classification: This gene should be rated amber as there are only two unrelated families reported with missense variants in KCTD15 and some functional evidence from structural analyses.

Created: 22 Oct 2025, 1:42 p.m. | Last Modified: 22 Oct 2025, 1:42 p.m.

Panel Version: 7.21

PMID:38296633 (2024) reported a two-generation family affected by a distinctive phenotype comprising a lipomatous frontonasal malformation, anosmia, cutis aplasia of the scalp and/or sparse hair, and congenital heart disease. A heterozygous c.310G>C variant encoding p.(Asp104His) within the BTB domain of KCTD15 was identified in the affected father and daughter via exome sequencing and the variant segregated with the phenotype. A de novo heterozygous c.263G>A variant encoding p.(Gly88Asp) was identified via targeted DNA sequencing in a similarly affected sporadic patient.

There is some functional evidence available from structural analyses, which demonstrated that missense substitutions act through a dominant negative mechanism by disrupting the higher order structure of the KCTD15 protein complex.

This gene has not yet been associated with any relevant phenotypes in OMIM (OMIM accessed on 22 October 2025) or in Gene2Phenotype.

Created: 22 Oct 2025, 1:38 p.m. | Last Modified: 22 Oct 2025, 1:40 p.m.

Panel Version: 7.19

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
frontonasal dysplasia, MONDO:0016643

Publications

• 38296633

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

I don't know

Sources: Literature

Created: 14 Oct 2025, 2:37 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Lipomatous frontonasal malformation; anosmia; cutis aplasia of the scalp; sparse hair; congenital heart disease

Publications

• PMID: 38296633

Mode of pathogenicity
Other