UXS1
protein-codingUDP-glucuronate decarboxylase 1, the group of Short chain dehydrogenase/reductase superfamily
Gene summary
This gene encodes an enzyme found in the perinuclear Golgi which catalyzes the synthesis of UDP-xylose used in glycosaminoglycan (GAG) synthesis on proteoglycans. The GAG chains are covalently attached to proteoglycans which participate in signaling pathways during development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~101.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0018230
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to UXS1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001253875.2. 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 | 3 | 1 | 4 | |||
| missense | 56 | 56 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 64 | 1 | 0 | 65 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001240804.1 | 15 | MANE Select | |
| Ensembl | ENSP00000283148.7 | 15 | MANE Select | |
| RefSeq | NP_001240805.1 | 9 | Standard | |
| RefSeq | NP_001364433.1 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| uxs1 | Danio rerio | Structure: chondrocyte Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Amino sugar and nucleotide sugar metabolism - Homo sapiens (human)
- Galactosemia III
- Galactosemia II (GALK)
- Nucleotide Sugars Metabolism
- UDP-D-xylose and UDP-D-glucuronate biosynthesis
Biological Process
- UDP-D-xylose biosynthetic process
- protein tetramerization
Molecular Function
- protein homodimerization activity
- UDP-glucuronate decarboxylase activity
- NAD+ binding
Cellular Component
- cytoplasm
- integral component of membrane
- Golgi cisterna membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000283148
- Coding exons
- 15
- Length
- 101037
- Individuals with no LoFs
- 124645
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 124660
- p
- 0.0000602
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.09 | 148 | 239 | 0.620 | 0.0000143 | 2776 |
| Missense (PolyPhen) | 52 | 109.8 | 0.47358 | 1154 | ||
| Synonymous | -0.368 | 96 | 91.5 | 1.05 | 0.00000634 | 766 |
| Loss of Function | 3.05 | 9 | 25.7 | 0.351 | 0.00000134 | 307 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000059 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000074 | 0.000071 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00017 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the NAD-dependent decarboxylation of UDP- glucuronic acid to UDP-xylose. Necessary for the biosynthesis of the core tetrasaccharide in glycosaminoglycan biosynthesis.;
Recessive Scores
- pRec
- 0.147
Intolerance Scores
- LoFtool
- 0.601
- RVIS EVS
- -0.56
- RVIS percentile EVS
- 19.31
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- K
- Indispensability pred.
- E
- Indispensability score
- 0.879
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |