NUDT4
protein-codingnudix hydrolase 4, the group of Nudix hydrolase family
Gene summary
The protein encoded by this gene regulates the turnover of diphosphoinositol polyphosphates. The turnover of these high-energy diphosphoinositol polyphosphates represents a molecular switching activity with important regulatory consequences. Molecular switching by diphosphoinositol polyphosphates may contribute to regulating intracellular trafficking. Several alternatively spliced transcript variants have been described, but the full-length nature of some variants has not been determined. Isoforms DIPP2alpha and DIPP2beta are distinguishable from each other solely by DIPP2beta possessing one additional amino acid due to intron boundary skidding in alternate splicing. [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 ~30.3 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 NUDT4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_019094.6. 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 | 0 | |||||
| missense | 16 | 16 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 16 | 0 | 0 | 16 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_061967.3 | 5 | MANE Select | |
| Ensembl | ENSP00000406612.2 | 5 | MANE Select | |
| RefSeq | NP_001287951.1 | 4 | Standard | |
| RefSeq | NP_001287952.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism
- Synthesis of pyrophosphates in the cytosol
- Inositol phosphate metabolism
Biological Process
- calcium-mediated signaling
- cyclic-nucleotide-mediated signaling
- intracellular signal transduction
- inositol phosphate metabolic process
- diphosphoinositol polyphosphate metabolic process
Molecular Function
- endopolyphosphatase activity
- protein binding
- diphosphoinositol-polyphosphate diphosphatase activity
- snoRNA binding
- bis(5'-adenosyl)-hexaphosphatase activity
Cellular Component
- nucleus
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000337179
- Coding exons
- 5
- Length
- 25366
- Individuals with no LoFs
- 124203
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 124205
- p
- 0.00000805
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.94 | 37 | 88.4 | 0.418 | 0.00000419 | 1113 |
| Missense (PolyPhen) | 11 | 31.675 | 0.34728 | 410 | ||
| Synonymous | 1.87 | 19 | 32.5 | 0.584 | 0.00000152 | 321 |
| Loss of Function | 2.58 | 1 | 9.64 | 0.104 | 4.91e-7 | 117 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate), PP-InsP4 and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction. Also able to catalyze the hydrolysis of dinucleoside oligophosphate Ap6A, but not Ap5A. The major reaction products are ADP and p4a from Ap6A. Also able to hydrolyze 5-phosphoribose 1-diphosphate. Does not play a role in U8 snoRNA decapping activity. Binds U8 snoRNA. {ECO:0000269|PubMed:10777568}.;
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- LoFtool
- 0.506
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 46.2
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.539
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Low | Low | Low |
| Cancer | Low | Low | Low |