SLC35A3
protein-codingsolute carrier family 35 member A3, the group of Solute carrier family 35
Gene summary
This gene encodes a UDP-N-acetylglucosamine transporter found in the golgi apparatus membrane. In cattle, a missense mutation in this gene causes complex vertebral malformation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~66.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014248
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0014248
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0014248
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014248
Submitter: Natera
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal; Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC35A3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012243.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 120 | 1 | 126 | ||
| missense | 1 | 79 | 2 | 82 | ||
| nonsense | 10 | 8 | 18 | |||
| start loss | 0 | |||||
| frameshift | 14 | 15 | 29 | |||
| splice donor/acceptor (+/-2bp) | 1 | 7 | 1 | 9 | ||
| Total | 25 | 31 | 85 | 120 | 3 | 264 |
Highest pathogenic variant AF is 0.00002643599
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036375.1 | 7 | MANE Select | |
| Ensembl | ENSP00000433849.1 | 7 | MANE Select | |
| RefSeq | NP_001258613.1 | 5 | Standard | |
| RefSeq | NP_001258614.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Transport of vitamins, nucleosides, and related molecules
- SLC-mediated transmembrane transport
- Transport of small molecules
- Galactose metabolism
- Transport of nucleotide sugars
Biological Process
- UDP-N-acetylglucosamine metabolic process
- carbohydrate transport
- UDP-N-acetylglucosamine transmembrane transport
Molecular Function
- UDP-N-acetylglucosamine transmembrane transporter activity
- protein binding
Cellular Component
- Golgi membrane
- Golgi apparatus
- integral component of Golgi membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000370155
- Coding exons
- 7
- Length
- 57191
- Individuals with no LoFs
- 125700
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 33
- Defined
- 125733
- p
- 0.000131
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.42 | 109 | 159 | 0.684 | 0.00000742 | 2059 |
| Missense (PolyPhen) | 19 | 34.353 | 0.55308 | 482 | ||
| Synonymous | 0.738 | 51 | 58.2 | 0.877 | 0.00000281 | 665 |
| Loss of Function | 2.17 | 7 | 16.5 | 0.423 | 8.45e-7 | 212 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00028 | 0.00027 | rare |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0.00014 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) transporter in the Golgi apparatus. May supply UDP-GlcNAc as substrate for Golgi-resident glycosyltransferases that generate branching of diantennary oligosaccharides. {ECO:0000269|PubMed:10393322}.;
- Disease
- DISEASE: Arthrogryposis, mental retardation, and seizures (AMRS) [MIM:615553]: A disease characterized by arthrogryposis, mental retardation, autism spectrum disorder, and epilepsy. Additional features include limb malformations, distal joint involvement, microcephaly, retromicrognathia, and general muscle hypotonia. {ECO:0000269|PubMed:24031089}. Note=The disease is caused by mutations affecting the gene represented in this entry. In Golgi vesicles isolated from patient fibroblasts the transport of the respective nucleotide sugar is significantly reduced causing a massive decrease in the content of cell surface expressed highly branched N-glycans and a concomitant sharp increase of lower branched glycoforms.;
Recessive Scores
- pRec
- 0.107
Intolerance Scores
- LoFtool
- 0.680
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.4
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.245
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |