Ectodermal dysplasia

Gene: KDF1

Green List (high evidence)

Comment on phenotypes: OMIM phenotype accessed 20th October 2025

Created: 20 Oct 2025, 1:40 p.m. | Last Modified: 20 Oct 2025, 1:40 p.m.

Panel Version: 4.10

Comment on list classification: Promoting to amber but with a recommendation for green rating following GMS review. There are multiple families with variants in this gene and an ectodermal phenotype.

Created: 20 Oct 2025, 1:40 p.m. | Last Modified: 20 Oct 2025, 1:40 p.m.

Panel Version: 4.9

Comment on mode of pathogenicity: There is a proposed mechanism of gain-of-function for the missense variants in this gene.

Created: 20 Oct 2025, 1:36 p.m. | Last Modified: 20 Oct 2025, 1:36 p.m.

Panel Version: 4.8

There is a provisional association with ?Ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type, OMIM:617337 in OMIM but the entry has not been updated since 2017 (accessed 20th October 2025).

In ClinGen there is a definitive association with KDF1 - ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type (https://search.clinicalgenome.org/CCID:008901)

Numerous cases reported e.g.

PMID: 27838789 - Shamseldin et al. 2017 - a multigenerational Saudi family with an autosomal dominant form of hypohidrotic ectodermal dysplasia who had a missense varient in KDF1 (c.753C>A;p.F251L) which segregated with the disease (7 affected, 6 non-affected). Hair, skin and teeth were affected. A mouse knockout of KDF1-/- (PMID: 24075906, 2013) shows an epidermal phenotype.                      

PMID: 30384154 - Zeng et al 2019 - missense variant in KDF1 identified in a family with non-syndromic tooth agenesis.

PMID: 30977908 - Manaspon et al 2019 - 5 year old Thai boy with ectodermal dysplasia - sparse hair, absent eyebrows and eyelashes, absence of sweating and dry skin. Using exome and sanger sequencing he was found to have a de novo heterozygous missense variant in KDF1

Further findings of KDF1 missense variants in ectodermal dysplasia patients are reported in PMIDs: 36293320, 37144643, 38501196, 40554824) spanning 2022 to 2025.
Sources: Literature

Created: 20 Oct 2025, 1:35 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
?Ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type, OMIM:617337; ectodermal dysplasia 12, hypohidrotic/hair/tooth/nail type, MONDO:0015024

Publications

• 27838789
• 24075906
• 30384154
• 30977908
• 36293320
• 37144643
• 38501196
• 40554824