IMPDH2
protein-codinginosine monophosphate dehydrogenase 2
Gene summary
This gene encodes the rate-limiting enzyme in the de novo guanine nucleotide biosynthesis. It is thus involved in maintaining cellular guanine deoxy- and ribonucleotide pools needed for DNA and RNA synthesis. The encoded protein catalyzes the NAD-dependent oxidation of inosine-5'-monophosphate into xanthine-5'-monophosphate, which is then converted into guanosine-5'-monophosphate. This gene is up-regulated in some neoplasms, suggesting it may play a role in malignant transformation. [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 ~5.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0700092
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Biochemical
Intervention: Pharmacogenomic
Rationale: Variants may be involved in response to treatment with medications such as mycophenolate mofetil in individuals who have undergone transplants
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IMPDH2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000884.3. 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 | 2 | 7 | |||
| missense | 5 | 66 | 71 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 4 | 5 | |||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 6 | 80 | 2 | 0 | 88 |
Highest pathogenic variant AF is 0.0000056257595
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000875.2 | 14 | MANE Select | |
| Ensembl | ENSP00000321584.4 | 14 | MANE Select | |
| RefSeq | NP_001397688.1 | 15 | Standard | |
| RefSeq | NP_001397689.1 | 14 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| impdh2 | Danio rerio | Structure: whole organism Quality: decreased length 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)
- Mycophenolic acid Pathway, Pharmacokinetics
- Mycophenolic acid Pathway, Pharmacokinetics/Pharmacodynamics
- Mycophenolic Acid Metabolism Pathway
Biological Process
- GMP biosynthetic process
- GTP biosynthetic process
- circadian rhythm
- purine ribonucleoside monophosphate biosynthetic process
- neutrophil degranulation
Molecular Function
- nucleotide binding
- DNA binding
- RNA binding
- IMP dehydrogenase activity
- protein binding
Cellular Component
- extracellular region
- nucleus
- cytoplasm
- peroxisomal membrane
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000326739
- Coding exons
- 14
- Length
- 5084
- Individuals with no LoFs
- 125690
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 58
- Defined
- 125748
- p
- 0.000231
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.50 | 176 | 297 | 0.592 | 0.0000173 | 3367 |
| Missense (PolyPhen) | 46 | 114.97 | 0.40011 | 1301 | ||
| Synonymous | -0.931 | 123 | 111 | 1.11 | 0.00000597 | 1021 |
| Loss of Function | 2.35 | 13 | 25.9 | 0.502 | 0.00000129 | 307 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00025 | rare |
| Latino/Admixed American | 0.00021 | 0.00020 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00055 | 0.00054 | rare |
| Finnish | 0.00020 | 0.00018 | rare |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0.00039 | 0.00039 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate- limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.;
Recessive Scores
- pRec
- 0.394
Intolerance Scores
- LoFtool
- 0.581
- RVIS EVS
- -0.65
- RVIS percentile EVS
- 16.36
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.975
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |