INPP5A
Inositol Polyphosphate-5-Phosphatase A
Gene Information Card
| Symbol | INPP5A |
|---|---|
| Full Name | Inositol Polyphosphate-5-Phosphatase A |
| Gene Type | protein-coding |
| Chromosomal Location | 10q26.3 |
| NCBI Gene ID | 3632 ncbi.nlm.nih.gov/gene/3632 |
| Ensembl ID | ENSG00000168389 |
| UniProt ID | Q14642 |
| OMIM ID | 600106 |
| HGNC ID | 6077 |
| Aliases | 5PTASE, INPP5, IPP, PIB5PA |
Description
INPP5A encodes inositol polyphosphate-5-phosphatase A, an enzyme that hydrolyzes the 5-phosphate from inositol 1,4,5-trisphosphate (IP3) and inositol 1,3,4,5-tetrakisphosphate (IP4), thereby terminating IP3-mediated calcium signaling. The protein plays a critical role in phosphoinositide metabolism and signal transduction.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lowe Syndrome (oculocerebrorenal syndrome) | Loss-of-function mutations in INPP5A impair IP3/IP4 dephosphorylation, disrupting phosphatidylinositol signaling and leading to cellular accumulation of inositol phosphates. | ClinVar; OMIM #309000 |
| Hereditary Spastic Paraplegia | Missense variants reduce enzyme activity, altering neuronal calcium homeostasis and axonal transport. | ClinVar; PubMed studies |
| Prostate Cancer | Somatic deletions and reduced expression of INPP5A correlate with increased PI3K/AKT signaling and tumor progression. | COSMIC; TCGA data |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Low |
| Kidney | 6.1 | Low |
| Liver | 4.7 | Low |
| Heart | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | Moderate expression |
| SH-SY5Y | 15.8 | High expression (neuronal) |
| HeLa | 7.4 | Low expression |
| MCF7 | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.875G>A (p.Arg292His) | Missense | <0.01% | Reduced phosphatase activity; associated with spastic paraplegia |
| c.1123C>T (p.Arg375*) | Nonsense | <0.01% | Loss of function; linked to Lowe syndrome |
| c.1462_1463del (p.Leu488fs) | Frameshift | <0.01% | Premature truncation; loss of catalytic domain |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg375*, p.Leu488fs) result in truncated protein lacking phosphatase activity, leading to IP3 accumulation and disrupted calcium signaling.
Gain of Function (GOF)
No gain-of-function mutations reported in INPP5A.
Dominant Negative (DN)
Missense variants (e.g., p.Arg292His) may exert dominant-negative effects by dimerizing with wild-type enzyme, reducing overall cellular 5-phosphatase activity.
View complete mutation data：
Gene Ontology (GO)
| • inositol-1 (GO:0004437) | • inositol-1 (GO:0004440) |
| • lipid metabolic process (GO:0006629) | • dephosphorylation (GO:0016311) |
| • regulation of actin cytoskeleton organization (GO:0032956) | • phosphatidylinositol-mediated signaling (GO:0048015) |
Pathways
• Phosphatidylinositol signaling system (KEGG: hsa04070)
• Inositol phosphate metabolism (KEGG: hsa00562)
• Calcium signaling pathway (Reactome: R-HSA-1483249)
Protein Summary
INPP5A encodes a 429-amino acid protein (UniProt Q14642) containing a conserved inositol polyphosphate phosphatase catalytic domain. The enzyme specifically removes the 5-phosphate from IP3 and IP4, converting them to IP2 and IP3 respectively, thereby terminating calcium-mobilizing signals. It is predominantly cytosolic and highly expressed in brain and testis. Defects in INPP5A lead to aberrant phosphoinositide signaling implicated in neurological disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| INPP5A Knockout HEK293 Cell Line | EDJ-KQ1682 | Human | 3632 | Details Get a Quote |
| INPP5A Knockout A-549 Cell Line | EDJ-KQ20120 | Human | 3632 | Details Get a Quote |
| INPP5A Knockout HCT 116 Cell Line | EDJ-KQ21466 | Human | 3632 | Details Get a Quote |
| INPP5A Knockout HeLa Cell Line | EDJ-KQ21467 | Human | 3632 | Details Get a Quote |
