Human Gene Module / Chromosome 1 / POMGNT1

POMGNT1protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-)

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
5 / 10
Rare Variants / Common Variants
21 / 0
EAGLE Score
1
Limited Learn More
Aliases
POMGNT1, RP11-322N21.3,  GNTI.2,  GnT I.2,  LGMD2O,  MDDGA3,  MDDGB3,  MDDGC3,  MEB,  MGAT1.2,  gnT-I.2
Associated Syndromes
-
Chromosome Band
1p34.1
Associated Disorders
-
Genetic Category
Rare Single Gene Mutation, Syndromic
Relevance to Autism

A homozygous missense variant in the POMGNT1 gene that was predicted to be damaging in silico was identifed in a male ASD proband born to consanguineous parents (Yu et al., 2013). Additional homozygous variants in the POMGNT1 gene had previously been identified in patients with a form of congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A3; MDDGA3; OMIM 253280), previously designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB), who also presented with severe autistic features (Haliloglu et al., 2004; Hehr et al., 2007).

Molecular Function

This gene encodes a type II transmembrane protein that resides in the Golgi apparatus. It participates in O-mannosyl glycosylation and is specific for alpha linked terminal mannose. Mutations in this gene may be associated with muscle-eye-brain disease and several congenital muscular dystrophies.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to POMGNT1 (10 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Clinical spectrum of muscle-eye-brain disease: from the typical presentation to severe autistic features Haliloglu G , et al. (2005) No -
2 Support Novel POMGnT1 mutations define broader phenotypic spectrum of muscle-eye-brain disease Hehr U , et al. (2007) No -
3 Primary Using whole-exome sequencing to identify inherited causes of autism Yu TW , et al. (2013) Yes -
4 Support Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders Li J , et al. (2017) Yes -
5 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
6 Support - Kritioti E et al. (2021) No Stereotypy
7 Support - Levchenko O et al. (2022) No -
8 Support - Zhou X et al. (2022) Yes -
9 Support - Cirnigliaro M et al. (2023) Yes -
10 Support - et al. () No -
Rare Variants   (21)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- p.Arg580Ter stop_gained Unknown - Simplex 17906881 Hehr U , et al. (2007)
c.290G>A p.Arg97Gln missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1539+1G>A - splice_site_variant Unknown - Simplex 17906881 Hehr U , et al. (2007)
c.1462C>T p.Arg488Ter stop_gained Familial Both parents Unknown 37799141 et al. ()
c.1721G>T p.Cys574Phe missense_variant Familial - Simplex 28831199 Li J , et al. (2017)
c.1814G>A p.Arg605His missense_variant Unknown - Simplex 17906881 Hehr U , et al. (2007)
c.304G>T p.Glu102Ter stop_gained Familial - Multiplex 34324503 Kritioti E et al. (2021)
c.385C>T p.Arg129Trp missense_variant Unknown - Unknown 35887114 Levchenko O et al. (2022)
c.25dup p.Leu9ProfsTer20 frameshift_variant Unknown - Simplex 17906881 Hehr U , et al. (2007)
c.385C>T p.Arg129Trp missense_variant Familial - Multiplex 34324503 Kritioti E et al. (2021)
c.462dup p.His155SerfsTer2 frameshift_variant Familial - Simplex 28831199 Li J , et al. (2017)
- p.Arg442Cys missense_variant Familial Both parents Multiplex 17906881 Hehr U , et al. (2007)
c.1540-2A>G - splice_site_variant Familial Both parents Simplex 17906881 Hehr U , et al. (2007)
c.643C>T p.Arg215Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.1735del p.Ile579PhefsTer45 frameshift_variant Familial - Simplex 28831199 Li J , et al. (2017)
c.593del p.Ser198ThrfsTer43 frameshift_variant Unknown - Simplex 17906881 Hehr U , et al. (2007)
c.1100G>A p.Arg367His missense_variant Familial Both parents Simplex 23352163 Yu TW , et al. (2013)
c.1324C>T p.Arg442Cys missense_variant Familial Both parents Simplex 17906881 Hehr U , et al. (2007)
c.1325G>A p.Arg442His missense_variant Familial Both parents Simplex 17906881 Hehr U , et al. (2007)
c.1350_1354del p.Trp451AlafsTer11 frameshift_variant Familial Both parents Simplex 17906881 Hehr U , et al. (2007)
c.793_796del p.Arg265GlyfsTer67 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M 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
S
icon
1

Increased from S to 1

New Scoring Scheme
Description

A homozygous missense variant in the POMGNT1 gene that was predicted to be damaging in silico was identifed in a male ASD proband born to consanguineous parents (Yu et al., 2013). Additional homozygous variants in the POMGNT1 gene had previously been identified in patients with a form of congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A3; MDDGA3; OMIM 253280), previously designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB), who also presented with severe autistic features (Haliloglu et al., 2004; Hehr et al., 2007).

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

Increased from S to S

Description

A homozygous missense variant in the POMGNT1 gene that was predicted to be damaging in silico was identifed in a male ASD proband born to consanguineous parents (Yu et al., 2013). Additional homozygous variants in the POMGNT1 gene had previously been identified in patients with a form of congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A3; MDDGA3; OMIM 253280), previously designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB), who also presented with severe autistic features (Haliloglu et al., 2004; Hehr et al., 2007).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
7/1/2018
icon
S

Increased from to S

Description

A homozygous missense variant in the POMGNT1 gene that was predicted to be damaging in silico was identifed in a male ASD proband born to consanguineous parents (Yu et al., 2013). Additional homozygous variants in the POMGNT1 gene had previously been identified in patients with a form of congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A3; MDDGA3; OMIM 253280), previously designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB), who also presented with severe autistic features (Haliloglu et al., 2004; Hehr et al., 2007).

Reports Added
[Clinical spectrum of muscle-eye-brain disease: from the typical presentation to severe autistic features.2005]
Krishnan Probability Score

Score 0.4306419083195

Ranking 20799/25841 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 1.6802369730346E-9

Ranking 16521/18225 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 0.8638870039517

Ranking 4016/18665 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 5

Ranking 290/461 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 0.097219397773057

Ranking 6200/20870 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
External PIN Data
BioGRIDHuman Protein Reference Database
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ADAM32 Disintegrin and metalloproteinase domain-containing protein 32 Human Protein Binding 203102 Q8TC27
MME membrane metallo-endopeptidase Human Protein Binding 4311 P08473
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