Human Gene Module / Chromosome 2 / UGGT1

UGGT1UDP-glucose glycoprotein glucosyltransferase 1

SFARI Gene Score
3S
Suggestive Evidence, Syndromic Criteria 3.1, Syndromic
Autism Reports / Total Reports
4 / 5
Rare Variants / Common Variants
17 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
2q14.3
Associated Disorders
-
Relevance to Autism

Dardas et al., 2025 described a cohort of 15 individuals from 10 unrelated families with bialleic variants in the UGGT1 gene presenting with a phenotypic spectrum ranging from fetal demise/infantile death and multiorgan system involvement to a complex syndromic neurodevelopmental disorder characterized by severe global developmental delay/intellectual disability, dysmorphic features, microcephaly, seizures, and behavioral traits including autism and stereotyped movements; functional studies of UGGT1 variants identified in affected individuals demonstrated diverse pathogenic mechanisms, inlcuding impaired UGGT1 glucosylation and catalyic activity, disrupted mRNA splicing, or inhibited endoplasmic reticulum retention. Multiple de novo variants in UGGT1, including two de novo loss-of-function variants, have been reported in ASD probands from the Autism Sequencing Consortium, the Simons Simplex Collection, and the SPARK cohort (De Rubeis et al., 2014; Iossifov et al., 2014; Zhou et al., 2022; Trost et al., 2022).

Molecular Function

UDP-glucose:glycoprotein glucosyltransferase (UGT) is a soluble protein of the endoplasmic reticulum (ER) that selectively reglucosylates unfolded glycoproteins, thus providing quality control for protein transport out of the ER.

External Links
Gene CardPubMed
Human
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SFARI Genomic Platforms
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Reports related to UGGT1 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Support - Zhou X et al. (2022) Yes -
4 Support - Trost B et al. (2022) Yes -
5 Primary - Zain Dardas et al. (2025) No ASD, stereotypy, ADHD
Rare Variants   (17)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2110C>T p.Arg704Ter stop_gained De novo - - 36368308 Trost B et al. (2022)
c.3105-1G>C p.? splice_site_variant De novo - - 35982159 Zhou X et al. (2022)
c.656A>G p.Asn219Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.4362T>C p.Asp1454= synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.4636C>T p.Arg1546Ter stop_gained Unknown - Simplex 40267907 Zain Dardas et al. (2025)
c.2489_2491del p.Ile830del inframe_deletion De novo - - 25363760 De Rubeis S , et al. (2014)
c.3998G>A p.Arg1333His missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.3464A>G p.Gln1155Arg missense_variant Unknown - Simplex 40267907 Zain Dardas et al. (2025)
c.381_384del p.Tyr127Ter stop_gained Familial Paternal Simplex 40267907 Zain Dardas et al. (2025)
c.4636C>T p.Arg1546Ter stop_gained Familial Both parents Simplex 40267907 Zain Dardas et al. (2025)
c.2168T>C p.Phe723Ser missense_variant Familial Paternal Simplex 40267907 Zain Dardas et al. (2025)
c.4636C>T p.Arg1546Ter stop_gained Familial Both parents Multiplex 40267907 Zain Dardas et al. (2025)
c.3815G>A p.Arg1272His missense_variant Familial Both parents Simplex 40267907 Zain Dardas et al. (2025)
c.2132C>T p.Ala711Val missense_variant Familial Both parents Multiplex 40267907 Zain Dardas et al. (2025)
c.4081dupC p.Gln1361ProfsTer27 frameshift_variant Familial Maternal Simplex 40267907 Zain Dardas et al. (2025)
c.1168_1191del p.Asp390_Gly397del inframe_deletion Familial Maternal Simplex 40267907 Zain Dardas et al. (2025)
c.978_979del p.Ser327PhefsTer13 frameshift_variant Familial Both parents Multiplex 40267907 Zain Dardas et al. (2025)
Common Variants  

No common variants reported.

SFARI Gene score
3S

Suggestive Evidence, Syndromic

criteria met
See SFARI Gene'scoring criteria
3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

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."

7/1/2025
3S

Initial score established: 3S

Krishnan Probability Score

Score 0.3290370314512

Ranking 25041/25841 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 0.0028972628133461

Ranking 11019/18225 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 0.80363595680127

Ranking 2273/18665 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 0.10073198333687

Ranking 6128/20870 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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