KDM1A

Chr 1

lysine demethylase 1A

Also known as: AIMAH3, AOF2, BHC110, CPRF, KDM1, LSD1

NCBI Gene: 23028 ENSG00000004487 UniProt: O60341

This protein functions as a histone demethylase and component of histone deacetylase complexes that silences gene expression. Loss-of-function mutations cause autosomal dominant cleft palate with psychomotor retardation and distinctive facial features, as well as ACTH-independent macronodular adrenal hyperplasia. The high constraint scores (pLI 0.997, LOEUF 0.276) support haploinsufficiency as the pathogenic mechanism.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCleft palate, psychomotor retardation, and distinctive facial features

UniProtACTH-independent macronodular adrenal hyperplasia 3

Clinical highlights

Gene-disease validity (ClinGen)

palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome · ADDefinitivesufficient evidence for diagnostic panels

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)

—

P/LP submissions

—

P/LP missense

0.28

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429