Human Gene Module / Chromosome 15 / TRPM1

TRPM1transient receptor potential cation channel subfamily M member 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 6
Rare Variants / Common Variants
13 / 0
Aliases
TRPM1, CSNB1C,  LTRPC1,  MLSN1
Associated Syndromes
-
Chromosome Band
15q13.3
Associated Disorders
-
Relevance to Autism

An enrichment of deletions of the TRPM1 gene were observed in ASD cases (5/2,588) compared to controls (0/2,670; Fisher's exact test p=0.029) (Girirajan et al., 2013).

Molecular Function

This gene encodes a member of the transient receptor potential melastatin subfamily of transient receptor potential ion channels. The encoded protein is a calcium permeable cation channel that is expressed in melanocytes and may play a role in melanin synthesis.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to TRPM1 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder Girirajan S , et al. (2013) Yes -
2 Support A survey of rare coding variants in candidate genes in schizophrenia by deep sequencing Hu X , et al. (2013) No -
3 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
4 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
5 Support - Cirnigliaro M et al. (2023) Yes -
6 Support - Thomas V Fernandez et al. (2023) No -
Rare Variants   (13)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.3115C>T p.Arg1039Ter stop_gained Unknown - Unknown 24126932 Hu X , et al. (2013)
- - copy_number_loss Familial Maternal Simplex 23375656 Girirajan S , et al. (2013)
- - copy_number_loss Familial Maternal Multiplex 23375656 Girirajan S , et al. (2013)
- - copy_number_loss Familial Paternal Multiplex 23375656 Girirajan S , et al. (2013)
- - copy_number_loss Familial Both parents Multiplex 23375656 Girirajan S , et al. (2013)
c.2433C>G p.Phe811Leu missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1016+1G>A - splice_site_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.3680+1G>T - splice_site_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.907G>A p.Val303Ile missense_variant De novo - Simplex 37788244 Thomas V Fernandez et al. (2023)
c.3681-1G>A - splice_site_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.4237G>T p.Glu1413Ter stop_gained Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1274_1275del p.Ile425SerfsTer62 frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.4224_4227del p.Asp1409LeufsTer11 frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

An enrichment of exon-disrupting deletions involving the TRPM1 gene was observed in ASD cases (5/2,588) compared to controls (0/2,670; Fisher's exact test p=0.029) (Girirajan et al., 2013); however, these deletions were inherited and displayed incomplete penetrance with ASD.

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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

An enrichment of exon-disrupting deletions involving the TRPM1 gene was observed in ASD cases (5/2,588) compared to controls (0/2,670; Fisher's exact test p=0.029) (Girirajan et al., 2013); however, these deletions were inherited and displayed incomplete penetrance with ASD.

Reports Added
[New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

An enrichment of exon-disrupting deletions involving the TRPM1 gene was observed in ASD cases (5/2,588) compared to controls (0/2,670; Fisher's exact test p=0.029) (Girirajan et al., 2013); however, these deletions were inherited and displayed incomplete penetrance with ASD.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
4/1/2016
icon
3

Increased from to 3

Description

An enrichment of exon-disrupting deletions involving the TRPM1 gene was observed in ASD cases (5/2,588) compared to controls (0/2,670; Fisher's exact test p=0.029) (Girirajan et al., 2013); however, these deletions were inherited and displayed incomplete penetrance with ASD.

Krishnan Probability Score

Score 0.52419350864827

Ranking 1635/25841 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 1.1683198065239E-31

Ranking 18166/18225 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 0.94946380702868

Ranking 18101/18665 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 -0.28232035792304

Ranking 16932/20870 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
CNVs associated with TRPM1(1 CNVs)
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15q13.3 80 Deletion-Duplication 117  /  452
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