SLC35A2

  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
SLC35A2 (HGNC:11022) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
solute carrier family 35 member A2
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
UGALT
Alias symbols
UGAT, UGT, UGT1, UGT2, UGTL, UDP-Gal-Tr
%HI
32.21(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.72(Read more about gnomAD pLI score)
LOEUF
0.56(Read more about gnomAD LOEUF score)
Cytoband
Xp11.23
Genomic Coordinates
GRCh37/hg19: chrX:48760460-48769235 NCBI Ensembl UCSC
GRCh38/hg38: chrX:48903183-48911958 NCBI Ensembl UCSC
MANE Select Transcript
NM_005660.3 ENST00000247138.11 (Read more about MANE Select)
Function
Transports uridine diphosphate galactose (UDP-galactose) from the cytosol into the Golgi apparatus, functioning as an antiporter that exchanges UDP-galactose for UMP (PubMed:9010752, PubMed:12682060). It is also able to exchange UDP-galactose for AMP and CMP, and to transport UDP-N-acetylgalactosamine (UDP-GalNAc) and other nucleotide sugars (PubMed:12682060, PubMed:11784306). As a provider of UDP- galactose to galactosyltransferases present in the Golgi apparatus, it is necessary for globotriao... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-25304
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
01/24/2018

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • SLC35A2-congenital disorder of glycosylation Monarch
HI Evidence:
  • PUBMED: 27743886
    2-month old girl had refractory epileptic spasms with hypsarrhythmia. She had developmental delay, widely spaced inverted nipples, external strabismus, and bilateral heterochromia of irises. MRI revealed cerebral and cerebellar atrophy, thinning of the corpus callosum, and arachnoid pouch. Whole-exome sequencing detected a de novo frameshift mutation c.950delG (p.Gly317Alafs*32) at exon 4 in SLC35A2. Seizures resolved by 3 years of age but she had intellectual disability.
  • PUBMED: 24115232
    In a cohort of 328 patients with early infantile epileptic encephalopathy, authors identified de novo frameshift mutations in SLC35A2 in two female patients: c.433_434del (p.Tyr145Profs*76) in patient 1 and c.972del (p.Phe324Leufs*25) in patient 2. A third female patient had a de novo missense mutation (c.638C>T [p.Ser213Phe]). X-inactivation analysis using a fragile X mental retardation locus methylation assay and human androgen receptor assay on genomic DNA from peripheral leukocytes showed a markedly skewed patternin patients 1 and 2 and was not informative in patient 3.
  • PUBMED: 23561849
    This report two male individuals with de novo mosaic mutations in SLC35A2 (p.Gly8Serfs∗9 and p.Val331Ile). A female with a de novo predicted loss-of-function mutation was also identified (p.Met1?). Three three patients showed an unusual transferrin profile, with loss of both galactose and sialic acid from multiple branches of complex type N-glycans. Functional analysis with fibroblast lines confirmed incomplete galactosylation, which leads to incomplete sialylation. By three years of age, the transferrin profile seems to revert to normal, despite worsening of the phenotype.
HI Evidence Comments:
SLC35A2 is an X-linked gene and heterozygous mutations appear to cause a phenotype in females with proven or predicted skewed X-inactivation. Affected males have mosaic de novo variants, suggesting that a constitutional mutation may be lethal. The common phenotype at a minimum includes seizures evolving to epileptic encephalopathy, developmental delay, hypsarrhythmia, intellectual disability, and ocular anomalies. Other relevant PMIDs: 25778940
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
No focal duplications of SLC35A2 described as of Jan 2018.
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Genomic View

Select assembly: (NC_000023.10) (NC_000023.11)