KDM1A

Chr 1AD

lysine demethylase 1A

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.282 OMIM phenotypes
Clinical SummaryKDM1A
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Gene-Disease Validity (ClinGen)
palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.28LOEUF
pLI 0.997
Z-score 5.46
OE 0.15 (0.080.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
4.68Z-score
OE missense 0.38 (0.340.43)
174 obs / 454.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.15 (0.080.28)
00.351.4
Missense OE0.38 (0.340.43)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 7 / 47.7Missense obs/exp: 174 / 454.7Syn Z: 1.57
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateKDM1A-related GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndromeLOFAD
strongKDM1A-related developmental delay and distinctive facial featuresOTHERAD
DN
0.2997th %ile
GOF
0.4184th %ile
LOF
0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.28

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KDM1A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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