KDM3A

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: LiferaOmics

Genetic evidence – Published (AR scope): No scorable published cases of biallelic (autosomal recessive) KDM3A variants causing neurodevelopmental disorder were identified in the current literature review. Available published human data primarily describe heterozygous (autosomal dominant) de novo variants, which are outside the scope of this AR GDR. Case-level = 0; segregation = 0; case-control = 0 Published (AD context; not scored for AR): PMID: 27748065 – Reports a heterozygous intragenic deletion involving KDM3A identified in an intellectual disability cohort; interpreted in an autosomal dominant framework. As this represents monoallelic/dominant evidence, it is not scorable under the autosomal recessive model. Case-level = 0 (AR scope); segregation = 0; case-control = 0 PMID: 36702863 – Whole-genome sequencing study identifying de novo heterozygous variants in KDM3A in individuals with autism spectrum disorder; association-level evidence under a dominant model and not applicable to AR scoring. Case-level = 0 (AR scope); segregation = 0; case-control = 0 AD-context evidence total (not scored for AR) = 0 Published genetic evidence total = 0/12 Genetic evidence – Our cases: Family 1 – one proband. Case-level (predicted loss-of-function variant in AR model; homozygous scored once; −0.5 consanguinity deduction applied) = 0.5; segregation = 0; case-control = 0; Family 1 total = 1.0 Our cases total = 1.0/12 Total genetic evidence (published AR + our cases) 1.0/12 Experimental evidence – Published: PMID: 29276005 – Demonstrates that KDM3A functions as an H3K9 demethylase regulating neuronal differentiation programs; knockdown experiments impair neurodevelopmental pathways with rescue supporting specificity. Function consistent with disease = 0.5 PMID: 29042477 – Shows that KDM3A is required for primary neurogenesis and Neurog2-mediated neuronal differentiation in Xenopus, with knockdown and rescue experiments supporting a critical role in neuronal development. Functional alteration in model system = 0.5 PMID: 40033066 – Mouse model studies demonstrate that Kdm3a regulates postnatal hippocampal neurogenesis and affects learning and memory, supporting relevance to neurodevelopmental processes. Model organism evidence = 0.5 Experimental evidence total = 1.5/6 Overall score Genetic evidence = 1.0 Experimental evidence = 1.5 Overall score = 2.5