Human Gene Module / Chromosome 10 / JMJD1C

JMJD1Cjumonji domain containing 1C

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
7 / 10
Rare Variants / Common Variants
22 / 0
Aliases
JMJD1C, TRIP8,  FLJ14374,  KIAA1380,  RP11-10C13.2,  DKFZp761F0118
Associated Syndromes
-
Chromosome Band
10q21.3
Associated Disorders
ADHD, ASD, EPS
Relevance to Autism

JMJD1C was originally hypothesized to be involved in autism based on a single case in which a patient with autism was found to have a de novo inversion which disrupted the JMJD1C gene (Castermans et al., 2007). A de novo double missense variant in JMJD1C was subquently identified in an ASD proband in Neale et al., 2012, and three additional missense variants in this gene were identified in ASD cases in Sez et al., 2016. De novo missense variants in JMJD1C were also identified in a patient with intellectual disability and a patient with Rett syndrome in Sez et al., 2016. Slavotinek et al., 2020 reported seven individuals with de novo JMJD1C variants; two of these individuals diangosed with ASD.

Molecular Function

histone demethylase, tumor suppressor

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to JMJD1C (10 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Identification and characterization of TRIP8 gene in silico Katoh M and Katoh M (2003) No -
2 Primary Identification and characterization of the TRIP8 and REEP3 genes on chromosome 10q21.3 as novel candidate genes for autism Castermans D , et al. (2007) Yes -
3 Recent Recommendation A novel variant of the putative demethylase gene, s-JMJD1C, is a coactivator of the AR Wolf SS , et al. (2007) No -
4 Support Patterns and rates of exonic de novo mutations in autism spectrum disorders Neale BM , et al. (2012) Yes -
5 Recent Recommendation Mutations in JMJD1C are involved in Rett syndrome and intellectual disability Sez MA , et al. (2015) Yes Rett syndrome
6 Recent Recommendation Low load for disruptive mutations in autism genes and their biased transmission Iossifov I , et al. (2015) Yes -
7 Support Genomic diagnosis for children with intellectual disability and/or developmental delay Bowling KM , et al. (2017) Yes -
8 Support Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes Guo H , et al. (2018) Yes -
9 Support Jumonji domain containing 1C (JMJD1C) sequence variants in seven patients with autism spectrum disorder, intellectual disability and seizures Slavotinek A , et al. (2020) No ASD, ADHD, epilepsy/seizures
10 Support - Zhou X et al. (2022) Yes -
Rare Variants   (22)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - translocation - - - 17290275 Castermans D , et al. (2007)
c.-221del - frameshift_variant Unknown - - 31954878 Slavotinek A , et al. (2020)
c.1675A>C p.Lys559Gln missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.488C>T p.Pro163Leu missense_variant De novo - - 26181491 Sez MA , et al. (2015)
c.3182G>A p.Ser1061Asn missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2830C>T p.Pro944Ser missense_variant Unknown - - 26181491 Sez MA , et al. (2015)
c.3308A>G p.Asn1103Ser missense_variant Unknown - - 26181491 Sez MA , et al. (2015)
c.3559A>G p.Thr1187Ala missense_variant De novo - - 26181491 Sez MA , et al. (2015)
c.3743A>G p.Gln1248Arg missense_variant Unknown - - 26181491 Sez MA , et al. (2015)
c.3982C>G p.Arg1328Gly missense_variant Unknown - - 26181491 Sez MA , et al. (2015)
c.6997A>G p.Thr2333Ala missense_variant Unknown - - 26181491 Sez MA , et al. (2015)
c.5863-6T>G - splice_region_variant De novo - - 31954878 Slavotinek A , et al. (2020)
c.6716G>A p.Trp2239Ter stop_gained De novo - Multiplex 35982159 Zhou X et al. (2022)
c.6410A>T p.Glu2137Val missense_variant Unknown - - 28554332 Bowling KM , et al. (2017)
c.349G>A p.Val117Ile missense_variant De novo - - 31954878 Slavotinek A , et al. (2020)
c.1100T>C p.Leu367Pro missense_variant De novo - - 31954878 Slavotinek A , et al. (2020)
c.5072A>G p.Asn1691Ser missense_variant De novo - - 31954878 Slavotinek A , et al. (2020)
c.1732A>G p.Ser578Gly missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.3487A>G p.Ile1163Val missense_variant De novo - Simplex 22495311 Neale BM , et al. (2012)
c.113dup p.Met38IlefsTer6 frameshift_variant De novo - Simplex 30504930 Guo H , et al. (2018)
c.536_552del p.Lys179ThrfsTer4 frameshift_variant De novo - - 31954878 Slavotinek A , et al. (2020)
c.2621_2661del p.Ser874CysfsTer10 frameshift_variant De novo - Multiplex 31954878 Slavotinek A , et al. (2020)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

JMJD1C was originally hypothesized to be involved in autism based on a single case in which a patient with autism was found to have a de novo inversion which disrupted the JMJD1C gene (PMID 17290275). More recently, a de novo double missense variant in JMJD1C was identified in an ASD proband in PMID 22495311, and three additional missense variants in this gene were identified in ASD cases in PMID 26181491. De novo missense variants in JMJD1C were identified in a patient with intellectual disability and a patient with Rett syndrome in PMID 26181491.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

JMJD1C was originally hypothesized to be involved in autism based on a single case in which a patient with autism was found to have a de novo inversion which disrupted the JMJD1C gene (PMID 17290275). More recently, a de novo double missense variant in JMJD1C was identified in an ASD proband in PMID 22495311, and three additional missense variants in this gene were identified in ASD cases in PMID 26181491. De novo missense variants in JMJD1C were identified in a patient with intellectual disability and a patient with Rett syndrome in PMID 26181491.

1/1/2020
3
icon
3

Decreased from 3 to 3

Description

JMJD1C was originally hypothesized to be involved in autism based on a single case in which a patient with autism was found to have a de novo inversion which disrupted the JMJD1C gene (PMID 17290275). More recently, a de novo double missense variant in JMJD1C was identified in an ASD proband in PMID 22495311, and three additional missense variants in this gene were identified in ASD cases in PMID 26181491. De novo missense variants in JMJD1C were identified in a patient with intellectual disability and a patient with Rett syndrome in PMID 26181491.

Reports Added
[Jumonji domain containing 1C (JMJD1C) sequence variants in seven patients with autism spectrum disorder, intellectual disability and seizures.2020]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

JMJD1C was originally hypothesized to be involved in autism based on a single case in which a patient with autism was found to have a de novo inversion which disrupted the JMJD1C gene (PMID 17290275). More recently, a de novo double missense variant in JMJD1C was identified in an ASD proband in PMID 22495311, and three additional missense variants in this gene were identified in ASD cases in PMID 26181491. De novo missense variants in JMJD1C were identified in a patient with intellectual disability and a patient with Rett syndrome in PMID 26181491.

Reports Added
[New Scoring Scheme]
10/1/2018
4
icon
4

Decreased from 4 to 4

Description

JMJD1C was originally hypothesized to be involved in autism based on a single case in which a patient with autism was found to have a de novo inversion which disrupted the JMJD1C gene (PMID 17290275). More recently, a de novo double missense variant in JMJD1C was identified in an ASD proband in PMID 22495311, and three additional missense variants in this gene were identified in ASD cases in PMID 26181491. De novo missense variants in JMJD1C were identified in a patient with intellectual disability and a patient with Rett syndrome in PMID 26181491.

Reports Added
[Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes.2018]
4/1/2017
4
icon
4

Decreased from 4 to 4

Description

JMJD1C was originally hypothesized to be involved in autism based on a single case in which a patient with autism was found to have a de novo inversion which disrupted the JMJD1C gene (PMID 17290275). More recently, a de novo double missense variant in JMJD1C was identified in an ASD proband in PMID 22495311, and three additional missense variants in this gene were identified in ASD cases in PMID 26181491. De novo missense variants in JMJD1C were identified in a patient with intellectual disability and a patient with Rett syndrome in PMID 26181491.

Reports Added
[Identification and characterization of the TRIP8 and REEP3 genes on chromosome 10q21.3 as novel candidate genes for autism.2007] [Patterns and rates of exonic de novo mutations in autism spectrum disorders.2012] [Identification and characterization of TRIP8 gene in silico.2003] [A novel variant of the putative demethylase gene, s-JMJD1C, is a coactivator of the AR.2007] [Mutations in JMJD1C are involved in Rett syndrome and intellectual disability.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]
1/1/2016
4
icon
4

Decreased from 4 to 4

Description

JMJD1C was originally hypothesized to be involved in autism based on a single case in which a patient with autism was found to have a de novo inversion which disrupted the JMJD1C gene (PMID 17290275). More recently, a de novo double missense variant in JMJD1C was identified in an ASD proband in PMID 22495311, and three additional missense variants in this gene were identified in ASD cases in PMID 26181491. De novo missense variants in JMJD1C were identified in a patient with intellectual disability and a patient with Rett syndrome in PMID 26181491.

Reports Added
[Identification and characterization of the TRIP8 and REEP3 genes on chromosome 10q21.3 as novel candidate genes for autism.2007] [Patterns and rates of exonic de novo mutations in autism spectrum disorders.2012] [Identification and characterization of TRIP8 gene in silico.2003] [A novel variant of the putative demethylase gene, s-JMJD1C, is a coactivator of the AR.2007] [Mutations in JMJD1C are involved in Rett syndrome and intellectual disability.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015]
7/1/2015
5
icon
4

Decreased from 5 to 4

Description

JMJD1C was originally hypothesized to be involved in autism based on a single case in which a patient with autism was found to have a de novo inversion which disrupted the JMJD1C gene (PMID 17290275). More recently, a de novo double missense variant in JMJD1C was identified in an ASD proband in PMID 22495311, and three additional missense variants in this gene were identified in ASD cases in PMID 26181491. De novo missense variants in JMJD1C were identified in a patient with intellectual disability and a patient with Rett syndrome in PMID 26181491.

Reports Added
[Identification and characterization of the TRIP8 and REEP3 genes on chromosome 10q21.3 as novel candidate genes for autism.2007] [Patterns and rates of exonic de novo mutations in autism spectrum disorders.2012] [Identification and characterization of TRIP8 gene in silico.2003] [A novel variant of the putative demethylase gene, s-JMJD1C, is a coactivator of the AR.2007] [Mutations in JMJD1C are involved in Rett syndrome and intellectual disability.2015]
7/1/2014
No data
icon
5

Increased from No data to 5

Description

JMJD1C is hypothesized to be involved in autism based on a single case in which a patient with autism was found to have a de novo inversion which disrupted the JMJD1C gene.

4/1/2014
No data
icon
5

Increased from No data to 5

Description

JMJD1C is hypothesized to be involved in autism based on a single case in which a patient with autism was found to have a de novo inversion which disrupted the JMJD1C gene.

Krishnan Probability Score

Score 0.49655686184545

Ranking 2567/25841 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 0.99999999996264

Ranking 59/18225 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
Iossifov Probability Score

Score 0.856

Ranking 185/239 scored genes


[Show Scoring Methodology]
Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists 239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This probability metric combines the evidence from de novo likely-gene- disrupting and missense mutations and assesses it against the background mutation rate in unaffected individuals from the University of Washington’s Exome Variant Sequence database (evs.gs.washington.edu/EVS/). The list of probability scores can be found here: www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/- /DCSupplemental/pnas.1516376112.sd02.xlsx
Original Source
Sanders TADA Score

Score 0.94898648927347

Ranking 17907/18665 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
Larsen Cumulative Evidence Score

Score 3

Ranking 348/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score 0.46237774454784

Ranking 806/20870 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
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
Cyp17a1 cytochrome P450, family 17, subfamily a, polypeptide 1 Mouse DNA Binding 13074 P27786
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