Relevance to Autism

To evaluate the effects of ASD-associated de novo variants in a family relative context, Kim et al., 2025 defined within-family standardized deviations (WFSD) by subtracting phenotype scores of unaffected family members and standardizing the result in 21,735 families from three ASD cohorts (the Korean Autism cohort, the Simons Simplex Collection, and SPARK); their analysis found that more genes enriched in de novo damaging protein-truncating variants (LOEUF < 0.37) and missense variants (MPC > 2) were identified using WFSD compared to raw phenotype scores, with 38 genes uniquely identified in the WFSD group, including the KDM1A gene. A de novo loss-of-function variant in the KDM1A gene was reported in a SPARK proband in Zhou et al., 2022, and de novo missense variants with MPC >2 in this gene were reported in an SSC proband and a proband from the Korean Autism cohort in Iossifov et al., 2014 and Kim et al., 2024, respectively.

Molecular Function

This gene encodes a nuclear protein containing a SWIRM domain, a FAD-binding motif, and an amine oxidase domain. This protein is a component of several histone deacetylase complexes, though it silences genes by functioning as a histone demethylase. Heterozygous variants in this gene are responsible for a syndrome of cleft palate, psychomotor retardation, and distinctive facial features (OMIM 616728).

External Links

References