INPP5F
protein-codinginositol polyphosphate-5-phosphatase F, the group of Phosphoinositide phosphatases
Gene summary
The protein encoded by this gene is an inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase and contains a Sac domain. The activity of this protein is specific for phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~103.1 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 INPP5F variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014937.4. 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 | 1 | 1 | 2 | |||
| missense | 139 | 1 | 140 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 1 | 0 | 146 | 2 | 0 | 149 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055752.1 | 20 | MANE Select | |
| Ensembl | ENSP00000497527.1 | 20 | MANE Select | |
| RefSeq | NP_001230123.1 | 6 | Standard | |
| RefSeq | NP_001230124.1 | 5 | Standard |
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)
- superpathway of D-<i>myo</i>-inositol (1,4,5)-trisphosphate metabolism
- Metabolism of lipids
- 3-phosphoinositide degradation
Biological Process
- positive regulation of receptor recycling
- phosphatidylinositol biosynthetic process
- adult locomotory behavior
- cardiac muscle hypertrophy in response to stress
- phosphatidylinositol catabolic process
Molecular Function
- protein binding
- inositol monophosphate 1-phosphatase activity
- phosphatidylinositol phosphate 5-phosphatase activity
- phosphatidylinositol phosphate 4-phosphatase activity
- protein homodimerization activity
Cellular Component
- early endosome
- clathrin-coated pit
- axon
- dendrite
- early endosome membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000361976
- Coding exons
- 20
- Length
- 103044
- Individuals with no LoFs
- 125651
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 97
- Defined
- 125748
- p
- 0.000386
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.35 | 503 | 596 | 0.844 | 0.0000304 | 7470 |
| Missense (PolyPhen) | 154 | 232.71 | 0.66176 | 3046 | ||
| Synonymous | -0.154 | 218 | 215 | 1.01 | 0.0000115 | 2097 |
| Loss of Function | 4.60 | 23 | 62.2 | 0.370 | 0.00000371 | 700 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00062 | 0.00062 | rare |
| Latino/Admixed American | 0.00038 | 0.00038 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00044 | 0.00044 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00043 | 0.00043 | rare |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inositol 4-phosphatase which mainly acts on phosphatidylinositol 4-phosphate. May be functionally linked to OCRL, which converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol, for a sequential dephosphorylation of phosphatidylinositol 4,5-bisphosphate at the 5 and 4 position of inositol, thus playing an important role in the endocytic recycling (PubMed:25869669). Regulator of TF:TFRC and integrins recycling pathway, is also involved in cell migration mechanisms (PubMed:25869669). Modulates AKT/GSK3B pathway by decreasing AKT and GSK3B phosphorylation (PubMed:17322895). Negatively regulates STAT3 signaling pathway through inhibition of STAT3 phosphorylation and translocation to the nucleus (PubMed:25476455). Functionally important modulator of cardiac myocyte size and of the cardiac response to stress (By similarity). May play a role as negative regulator of axon regeneration after central nervous system injuries (By similarity). {ECO:0000250|UniProtKB:Q8CDA1, ECO:0000269|PubMed:17322895, ECO:0000269|PubMed:25476455, ECO:0000269|PubMed:25869669}.;
Intolerance Scores
- LoFtool
- 0.952
- RVIS EVS
- -0.79
- RVIS percentile EVS
- 12.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.205
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |