GMPS
protein-codingguanine monophosphate synthase, the group of Glutamine amidotransferase class 1 domain containing
Gene summary
In the de novo synthesis of purine nucleotides, IMP is the branch point metabolite at which point the pathway diverges to the synthesis of either guanine or adenine nucleotides. In the guanine nucleotide pathway, there are 2 enzymes involved in converting IMP to GMP, namely IMP dehydrogenase (IMPD1), which catalyzes the oxidation of IMP to XMP, and GMP synthetase, which catalyzes the amination of XMP to GMP. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~73.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GMPS variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003875.3. 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 | 3 | 3 | ||||
| missense | 62 | 1 | 63 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 67 | 0 | 4 | 71 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003866.1 | 16 | MANE Select | |
| Ensembl | ENSP00000419851.1 | 16 | MANE Select | |
| Ensembl | ENSP00000295920.7 | 14 | Standard | |
| Ensembl | ENSP00000295920.7 | 14 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| gmps | Danio rerio | Structure: iridophore Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Drug metabolism - other enzymes - Homo sapiens (human)
- Purine metabolism - Homo sapiens (human)
- Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics
- Purine Nucleoside Phosphorylase Deficiency
- Mercaptopurine Action Pathway
Biological Process
- GMP biosynthetic process
- glutamine metabolic process
- purine nucleobase biosynthetic process
- purine ribonucleoside monophosphate biosynthetic process
Molecular Function
- GMP synthase activity
- GMP synthase (glutamine-hydrolyzing) activity
- ATP binding
- pyrophosphatase activity
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000496455
- Coding exons
- 16
- Length
- 73491
- Individuals with no LoFs
- 124642
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 124651
- p
- 0.0000361
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.37 | 228 | 353 | 0.645 | 0.0000174 | 4522 |
| Missense (PolyPhen) | 66 | 145.51 | 0.45359 | 1834 | ||
| Synonymous | 1.12 | 101 | 116 | 0.868 | 0.00000553 | 1332 |
| Loss of Function | 4.73 | 3 | 31.7 | 0.0945 | 0.00000165 | 430 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000065 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000045 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the de novo synthesis of guanine nucleotides which are not only essential for DNA and RNA synthesis, but also provide GTP, which is involved in a number of cellular processes important for cell division.;
- Disease
- DISEASE: Note=A chromosomal aberration involving GMPS is found in acute myeloid leukemias. Translocation t(3,11)(q25,q23) with KMT2A/MLL1.;
Recessive Scores
- pRec
- 0.533
Intolerance Scores
- LoFtool
- 0.252
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 35.99
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.987
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |