Human Gene Module / Chromosome 1 / ALG6

ALG6ALG6, alpha-1,3-glucosyltransferase

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
0 / 2
Rare Variants / Common Variants
1 / 0
Aliases
ALG6, CDG1C
Associated Syndromes
-
Chromosome Band
1p31.3
Associated Disorders
ASD
Relevance to Autism

Evaluation of the clinical data from 41 patients with congenital disorder of glycosylation, type Ic, mediated by ALG6 mutations (ALG6-CDG) found that behavioral problems or mood disorders occurred in 14 patients, with most of these 14 patients showing autistic features. Furthermore, five patients with ALG6-CDG were diagnosed with autism (Morava et al., 2016).

Molecular Function

This gene encodes a member of the ALG6/ALG8 glucosyltransferase family that catalyzes the addition of the first glucose residue to the growing lipid-linked oligosaccharide precursor of N-linked glycosylation. Mutations in this gene are associated with congenital disorder of glycosylation, type Ic (CDG1C; OMIM 603147), a multisystem disorder resulting in a wide variety of clinical features, including developmental delay, hypotonia, epilepsy, ataxia, and failure to thrive.

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Reports related to ALG6 (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary ALG6-CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavioral and limb anomalies Morava E , et al. (2016) No ASD or autistic features
2 Support - Brea-Fernández AJ et al. (2022) No -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.998C>T p.Ala333Val missense_variant Familial Both parents - 35322241 Brea-Fernández AJ et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Evaluation of the clinical data from 41 patients with congenital disorder of glycosylation, type Ic, mediated by ALG6 mutations (ALG6-CDG) found that behavioral problems or mood disorders occurred in 14 patients, with most of these 14 patients showing autistic features. Furthermore, five patients with ALG6-CDG were diagnosed with autism (Morava et al., 2016).

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
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
S

Score remained at S

New Scoring Scheme
Description

Evaluation of the clinical data from 41 patients with congenital disorder of glycosylation, type Ic, mediated by ALG6 mutations (ALG6-CDG) found that behavioral problems or mood disorders occurred in 14 patients, with most of these 14 patients showing autistic features. Furthermore, five patients with ALG6-CDG were diagnosed with autism (Morava et al., 2016).

Reports Added
[New Scoring Scheme]
Krishnan Probability Score

Score 0.33273405408519

Ranking 24601/25841 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 0.055367626172513

Ranking 8446/18225 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 0.85320061993134

Ranking 3579/18665 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 0.19927402212809

Ranking 4278/20870 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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