Human Gene Module / Chromosome 9 / POMT1

POMT1protein O-mannosyltransferase 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
17 / 0
Aliases
POMT1, LGMD2K,  MDDGA1,  MDDGB1,  MDDGC1,  RT
Associated Syndromes
-
Chromosome Band
9q34.13
Associated Disorders
-
Relevance to Autism

Rare inherited loss-of-function and damaging missense variants in the POMT1 gene were identified in ASD probands from the Simons Simplex Collection in Krumm et al., 2015; targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified additional rare inherited variants in this gene in ASD probands. Subsequent Transmission and De Novo Association (TADA) analysis In Guo et al., 2017 identified POMT1 as an ASD candidate gene with a PTADA of 0.007923 in the Chinese ASD case-control cohort and a PTADA of 0.009218 in a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

Molecular Function

The protein encoded by this gene is an O-mannosyltransferase that requires interaction with the product of the POMT2 gene for enzymatic function. The encoded protein is found in the membrane of the endoplasmic reticulum. Biallelic mutations in the POMT1 gene are associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 (OMIM 236670), muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 (OMIM 613155), and muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 (OMIM 609308).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to POMT1 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Excess of rare, inherited truncating mutations in autism Krumm N , et al. (2015) Yes -
2 Recent Recommendation Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders Li J , et al. (2017) Yes -
3 Recent Recommendation A multidimensional precision medicine approach identifies an autism subtype characterized by dyslipidemia Luo Y et al. (2020) Yes -
4 Support - Balasar et al. (2023) No -
Rare Variants   (17)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.699+52C>T - intron_variant Familial - - 32778826 Luo Y et al. (2020)
c.986+1G>A - splice_site_variant Familial - - 28831199 Li J , et al. (2017)
c.1792C>T p.Arg598Ter stop_gained Familial - - 32778826 Luo Y et al. (2020)
c.35C>T p.Thr12Met missense_variant Familial - - 28831199 Li J , et al. (2017)
c.946C>T p.Pro316Ser missense_variant Familial - - 28831199 Li J , et al. (2017)
c.1444C>T p.His482Tyr missense_variant De novo - - 28831199 Li J , et al. (2017)
c.2114C>T p.Ser705Leu missense_variant Familial - - 28831199 Li J , et al. (2017)
c.903del p.Phe301LeufsTer7 frameshift_variant Familial - - 32778826 Luo Y et al. (2020)
c.428A>T p.Glu143Val missense_variant Familial Paternal Simplex 25961944 Krumm N , et al. (2015)
c.817G>A p.Asp273Asn missense_variant Familial Paternal Simplex 25961944 Krumm N , et al. (2015)
c.1150G>A p.Gly384Ser missense_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
c.1892C>T p.Pro631Leu missense_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
c.2168G>A p.Arg723Gln missense_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
c.83T>C p.Leu28Pro missense_variant Familial Both parents Multiplex 37524782 Balasar et al. (2023)
c.2101dup p.Asp701GlyfsTer8 frameshift_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
c.2096_2097insG p.Tyr699Ter frameshift_variant Familial Paternal Simplex 25961944 Krumm N , et al. (2015)
c.578_579del p.Thr193ArgfsTer138 frameshift_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Rare inherited loss-of-function and damaging missense variants in the POMT1 gene were identified in ASD probands from the Simons Simplex Collection in Krumm et al., 2015; targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified additional rare inherited variants in this gene in ASD probands. Subsequent Transmission and De Novo Association (TADA) analysis In Guo et al., 2017 identified POMT1 as an ASD candidate gene with a PTADA of 0.007923 in the Chinese ASD case-control cohort and a PTADA of 0.009218 in a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium. Biallelic mutations in the POMT1 gene are associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 (OMIM 236670), muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 (OMIM 613155), and muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 (OMIM 609308).

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

Rare inherited loss-of-function and damaging missense variants in the POMT1 gene were identified in ASD probands from the Simons Simplex Collection in Krumm et al., 2015; targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified additional rare inherited variants in this gene in ASD probands. Subsequent Transmission and De Novo Association (TADA) analysis In Guo et al., 2017 identified POMT1 as an ASD candidate gene with a PTADA of 0.007923 in the Chinese ASD case-control cohort and a PTADA of 0.009218 in a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium. Biallelic mutations in the POMT1 gene are associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 (OMIM 236670), muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 (OMIM 613155), and muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 (OMIM 609308).

7/1/2020
3
icon
3

Decreased from 3 to 3

Description

Rare inherited loss-of-function and damaging missense variants in the POMT1 gene were identified in ASD probands from the Simons Simplex Collection in Krumm et al., 2015; targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified additional rare inherited variants in this gene in ASD probands. Subsequent Transmission and De Novo Association (TADA) analysis In Guo et al., 2017 identified POMT1 as an ASD candidate gene with a PTADA of 0.007923 in the Chinese ASD case-control cohort and a PTADA of 0.009218 in a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium. Biallelic mutations in the POMT1 gene are associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 (OMIM 236670), muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 (OMIM 613155), and muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 (OMIM 609308).

Reports Added
[A multidimensional precision medicine approach identifies an autism subtype characterized by dyslipidemia2020]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Rare inherited loss-of-function and damaging missense variants in the POMT1 gene were identified in ASD probands from the Simons Simplex Collection in Krumm et al., 2015; targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified additional rare inherited variants in this gene in ASD probands. Subsequent Transmission and De Novo Association (TADA) analysis In Guo et al., 2017 identified POMT1 as an ASD candidate gene with a PTADA of 0.007923 in the Chinese ASD case-control cohort and a PTADA of 0.009218 in a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium. Biallelic mutations in the POMT1 gene are associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 (OMIM 236670), muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 (OMIM 613155), and muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 (OMIM 609308).

Reports Added
[New Scoring Scheme]
7/1/2017
icon
4

Increased from to 4

Description

Rare inherited loss-of-function and damaging missense variants in the POMT1 gene were identified in ASD probands from the Simons Simplex Collection in Krumm et al., 2015; targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified additional rare inherited variants in this gene in ASD probands. Subsequent Transmission and De Novo Association (TADA) analysis In Guo et al., 2017 identified POMT1 as an ASD candidate gene with a PTADA of 0.007923 in the Chinese ASD case-control cohort and a PTADA of 0.009218 in a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium. Biallelic mutations in the POMT1 gene are associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 (OMIM 236670), muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 (OMIM 613155), and muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 (OMIM 609308).

Krishnan Probability Score

Score 0.44002598047763

Ranking 19631/25841 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 4.9983547425292E-10

Ranking 16714/18225 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 0.9475886505868

Ranking 17337/18665 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 -0.17006221984601

Ranking 14706/20870 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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