INPP5B
protein-codinginositol polyphosphate-5-phosphatase B, the group of Phosphoinositide phosphatases
Gene summary
This gene encodes a member of a family of inositol polyphosphate-5-phosphatases. These enzymes function in the regulation of calcium signaling by inactivating inositol phosphates. The encoded protein is localized to the cytosol and mitochondria, and associates with membranes through an isoprenyl modification near the C-terminus. Alternatively spliced transcript variants of this gene have been described. [provided by RefSeq, Jul 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~86.4 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 INPP5B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005540.3. 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 | 6 | 9 | |||
| missense | 1 | 139 | 5 | 2 | 147 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 1 | 149 | 12 | 2 | 164 |
Highest pathogenic variant AF is 0.000017364255
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005531.2 | 23 | MANE Select | |
| Ensembl | ENSP00000362115.3 | 23 | MANE Select | |
| RefSeq | NP_001284363.1 | 18 | Standard | |
| RefSeq | NP_001337156.1 | 16 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| inpp5b | Danio rerio | Structure: post-vent region Quality: kinked abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Inositol phosphate metabolism - Homo sapiens (human)
- Phosphatidylinositol signaling system - Homo sapiens (human)
- Signal Transduction
- D-<i>myo</i>-inositol (1,3,4)-trisphosphate biosynthesis
- superpathway of D-<i>myo</i>-inositol (1,4,5)-trisphosphate metabolism
Biological Process
- signal transduction
- positive regulation of GTPase activity
- inositol phosphate metabolic process
- inositol phosphate dephosphorylation
- phosphatidylinositol dephosphorylation
Molecular Function
- phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity
- GTPase activator activity
- protein binding
- metal ion binding
- inositol-1,4,5-trisphosphate 5-phosphatase activity
Cellular Component
- endoplasmic reticulum-Golgi intermediate compartment
- Golgi apparatus
- cytosol
- plasma membrane
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000373024
- Coding exons
- 23
- Length
- 86361
- Individuals with no LoFs
- 124241
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 557
- Defined
- 124799
- p
- 0.00224
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.11 | 436 | 507 | 0.861 | 0.0000270 | 6050 |
| Missense (PolyPhen) | 150 | 200.32 | 0.74878 | 2508 | ||
| Synonymous | 1.22 | 175 | 197 | 0.890 | 0.0000110 | 1683 |
| Loss of Function | 2.54 | 33 | 52.9 | 0.623 | 0.00000291 | 575 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00084 | 0.00084 | rare |
| Latino/Admixed American | 0.0013 | 0.0013 | notable |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0.00045 | 0.00039 | rare |
| Finnish | 0.0039 | 0.0039 | notable |
| European (Non-Finnish) | 0.0030 | 0.0030 | notable |
| South Asian | 0.0020 | 0.0020 | notable |
| Other | 0.00083 | 0.00082 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events. {ECO:0000269|PubMed:7721860}.;
Recessive Scores
- pRec
- 0.127
Intolerance Scores
- LoFtool
- 0.290
- RVIS EVS
- -0.91
- RVIS percentile EVS
- 10.07
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.271
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |