UMPS
protein-codinguridine monophosphate synthetase, the group of MicroRNA protein coding host genes
Gene summary
This gene encodes a uridine 5'-monophosphate synthase. The encoded protein is a bifunctional enzyme that catalyzes the final two steps of the de novo pyrimidine biosynthetic pathway. The first reaction is carried out by the N-terminal enzyme orotate phosphoribosyltransferase which converts orotic acid to orotidine-5'-monophosphate. The terminal reaction is carried out by the C-terminal enzyme OMP decarboxylase which converts orotidine-5'-monophosphate to uridine monophosphate. Defects in this gene are the cause of hereditary orotic aciduria. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~18.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0009797
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0009797
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0009797
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0009797
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0009797
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0009797
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Biochemical; Hematologic; Neurologic
Intervention: Biochemical
Rationale: Pyrimidine replacement therapy, along with urinary orotic acid monitoring, can be beneficial
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to UMPS variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000373.4. 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 | 4 | 30 | 3 | 37 | ||
| missense | 1 | 3 | 76 | 6 | 1 | 87 |
| nonsense | 1 | 2 | 1 | 4 | ||
| start loss | 2 | 2 | ||||
| frameshift | 1 | 1 | 3 | 5 | ||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 3 | 6 | 90 | 36 | 4 | 139 |
Highest pathogenic variant AF is 0.00031596358
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000364.1 | 6 | MANE Select | |
| Ensembl | ENSP00000232607.2 | 6 | MANE Select | |
| Ensembl | ENSP00000420409.1 | 2 | Standard | |
| Ensembl | ENSP00000417893.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Pyrimidine metabolism - Homo sapiens (human)
- Drug metabolism - other enzymes - Homo sapiens (human)
- Fluoropyrimidine Pathway, Pharmacokinetics
- Fluoropyrimidine Activity
- Pyrimidine metabolism
Biological Process
- 'de novo' pyrimidine nucleobase biosynthetic process
- UMP biosynthetic process
- female pregnancy
- lactation
- cellular response to drug
Molecular Function
- orotate phosphoribosyltransferase activity
- orotidine-5'-phosphate decarboxylase activity
Cellular Component
- nucleus
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000232607
- Coding exons
- 6
- Length
- 14828
- Individuals with no LoFs
- 125722
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 26
- Defined
- 125748
- p
- 0.000103
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.14 | 216 | 268 | 0.805 | 0.0000141 | 3107 |
| Missense (PolyPhen) | 53 | 80.839 | 0.65562 | 933 | ||
| Synonymous | 0.256 | 99 | 102 | 0.968 | 0.00000550 | 999 |
| Loss of Function | 1.78 | 9 | 16.9 | 0.533 | 9.01e-7 | 212 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00032 | 0.00031 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Disease
- DISEASE: Orotic aciduria 1 (ORAC1) [MIM:258900]: A disorder of pyrimidine metabolism resulting in megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. A minority of cases have additional features, particularly congenital malformations and immune deficiencies. {ECO:0000269|PubMed:9042911}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.272
Intolerance Scores
- LoFtool
- 0.579
- RVIS EVS
- -0.42
- RVIS percentile EVS
- 25.56
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.712
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |