Human Gene Module / Chromosome 1 / KDM1A

KDM1Alysine demethylase 1A

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
5 / 6
Rare Variants / Common Variants
5 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
1p36.12
Associated Disorders
-
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).

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Reports related to KDM1A (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Support - Zhou X et al. (2022) Yes -
3 Support - Soo-Whee Kim et al. (2024) Yes -
4 Primary - Soo-Whee Kim et al. (2025) Yes -
5 Support - Ana M Martín-González et al. () No -
6 Support - Gabriela Repiská et al. (2025) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.884-5T>G - stop_gained De novo - Simplex 35982159 Zhou X et al. (2022)
c.1006C>T p.Arg336Ter stop_gained De novo - Simplex 35982159 Zhou X et al. (2022)
c.196C>T p.Pro66Ser missense_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
c.2492A>G p.Tyr831Cys missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.557A>G p.Tyr186Cys missense_variant Unknown - - 40869941 Gabriela Repiská et al. (2025)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

criteria met
See SFARI Gene'scoring criteria
3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2025
3

Initial score established: 3

Krishnan Probability Score

Score 0.44446175642826

Ranking 15967/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.99102796468651

Ranking 1761/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.76184938080132

Ranking 1679/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.32750080723238

Ranking 2325/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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