Human Gene Module / Chromosome 5 / KDM3B

KDM3Blysine demethylase 3B

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
3 / 6
Rare Variants / Common Variants
23 / 0
EAGLE Score
1.5
Limited Learn More
Aliases
KDM3B, 5qNCA,  C5orf7,  JMJD1B,  NET22
Associated Syndromes
-
Chromosome Band
5q31.2
Associated Disorders
ADHD, ASD
Genetic Category
Rare Single Gene Mutation, Syndromic
Relevance to Autism

Diets et al., 2019 reported de novo and inherited pathogenic variants in the KDM3B gene in 14 unrelated individuals and three affected parents with varying degrees of intellectual disability (ID) or developmental delay (DD) and short stature; behavioral problems were noted in eight individuals, with three individuals diagnosed with autism spectrum disorder and four individuals diagnosed with ADHD.

Molecular Function

Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Demethylation of Lys residue generates formaldehyde and succinate. May have tumor suppressor activity.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to KDM3B (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De Novo and Inherited Pathogenic Variants in KDM3B Cause Intellectual Disability, Short Stature, and Facial Dysmorphism Diets IJ , et al. (2019) No ASD, ADHD
2 Support - Balan S et al. (2021) Yes -
3 Support - Zhou X et al. (2022) Yes -
4 Support - Thomas V Fernandez et al. (2023) No -
5 Support - Marketa Wayhelova et al. (2024) Yes -
6 Support - Axel Schmidt et al. (2024) No -
Rare Variants   (23)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.133C>T p.Arg45Ter stop_gained De novo - - 30929739 Diets IJ , et al. (2019)
c.2479C>T p.Gln827Ter stop_gained Unknown - - 30929739 Diets IJ , et al. (2019)
c.4549C>T p.Arg1517Ter stop_gained De novo - - 30929739 Diets IJ , et al. (2019)
c.2762G>A p.Arg921Gln missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1819C>T p.Arg607Trp missense_variant Unknown - - 34262135 Balan S et al. (2021)
c.349T>C p.Trp117Arg missense_variant De novo - - 30929739 Diets IJ , et al. (2019)
c.2827C>T p.Arg943Trp missense_variant De novo - - 30929739 Diets IJ , et al. (2019)
c.2828G>A p.Arg943Gln missense_variant De novo - - 30929739 Diets IJ , et al. (2019)
c.3083G>A p.Arg1028Gln missense_variant De novo - - 30929739 Diets IJ , et al. (2019)
c.3095A>T p.Asp1032Val missense_variant De novo - - 30929739 Diets IJ , et al. (2019)
c.4526T>C p.Leu1509Pro missense_variant De novo - - 30929739 Diets IJ , et al. (2019)
c.4631A>G p.Tyr1544Cys missense_variant De novo - - 30929739 Diets IJ , et al. (2019)
c.5201T>G p.Leu1734Arg missense_variant De novo - - 30929739 Diets IJ , et al. (2019)
c.277G>T p.Glu93Ter stop_gained Familial Maternal - 30929739 Diets IJ , et al. (2019)
c.2361del p.Asn787LysfsTer8 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.3514A>C p.Thr1172Pro missense_variant Familial Maternal - 34262135 Balan S et al. (2021)
c.5014G>A p.Ala1672Thr missense_variant Familial Maternal - 34262135 Balan S et al. (2021)
c.2743_2745del p.Arg915del inframe_deletion De novo - - 39039281 Axel Schmidt et al. (2024)
c.1007A>G p.Asp336Gly missense_variant Familial Maternal - 30929739 Diets IJ , et al. (2019)
c.5191G>A p.Glu1731Lys missense_variant Familial Paternal - 30929739 Diets IJ , et al. (2019)
c.1211_1212del p.Lys404ArgfsTer74 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.370C>A p.Pro124Thr missense_variant De novo - Simplex 38321498 Marketa Wayhelova et al. (2024)
c.4541A>C p.Tyr1514Ser missense_variant De novo - Simplex 37788244 Thomas V Fernandez et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
1S

High Confidence, Syndromic

Score Delta: Score remained at 1S

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

10/1/2019
icon
1

Increased from to 1

New Scoring Scheme
Description

Diets et al., 2019 reported de novo and inherited pathogenic variants in the KDM3B gene in 14 unrelated individuals and three affected parents with varying degrees of intellectual disability (ID) or developmental delay (DD) and short stature; behavioral problems were noted in eight individuals, with three individuals diagnosed with autism spectrum disorder and four individuals diagnosed with ADHD.

Reports Added
[New Scoring Scheme]
Krishnan Probability Score

Score 0.49633227094966

Ranking 2622/25841 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 0.99999999907823

Ranking 98/18225 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 0.93388554602712

Ranking 12402/18665 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 0.3850172718132

Ranking 1621/20870 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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