INPP5D
inositol polyphosphate-5-phosphatase D, the group of SH2 domain containing|Phosphoinositide phosphatases
Basic information
Region (hg38): 2:233059967-233207903
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the INPP5D gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | |||||
| missense | 2 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 3 | 0 | 1 |
Variants in INPP5D
This is a list of pathogenic ClinVar variants found in the INPP5D region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 2-233125768-G-A | not specified | Uncertain significance (Dec 12, 2023) | ||
| 2-233125822-G-C | not specified | Uncertain significance (Apr 27, 2024) | ||
| 2-233125855-G-A | not specified | Uncertain significance (Sep 17, 2021) | ||
| 2-233163762-A-G | Benign (Jun 01, 2023) | |||
| 2-233163905-T-C | Severe combined immunodeficiency disease | Uncertain significance (Mar 23, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| INPP5D | protein_coding | protein_coding | ENST00000359570 | 28 | 191873 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.972 | 0.0280 | 124621 | 0 | 51 | 124672 | 0.000205 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 4.15 | 387 | 695 | 0.557 | 0.0000425 | 7678 |
| Missense in Polyphen | 107 | 263.6 | 0.40592 | 2890 | ||
| Synonymous | 0.948 | 284 | 305 | 0.931 | 0.0000218 | 2268 |
| Loss of Function | 5.83 | 11 | 59.5 | 0.185 | 0.00000288 | 717 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000217 | 0.000216 |
| Ashkenazi Jewish | 0.000199 | 0.000199 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.000140 | 0.000139 |
| European (Non-Finnish) | 0.000339 | 0.000336 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000981 | 0.0000980 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol- 3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Acts as a negative regulator of myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. Regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and is required for endotoxin tolerance. Involved in the control of cell-cell junctions, CD32a signaling in neutrophils and modulation of EGF-induced phospholipase C activity. Key regulator of neutrophil migration, by governing the formation of the leading edge and polarization required for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells. Mediates the activin/TGF-beta-induced apoptosis through its Smad-dependent expression. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. {ECO:0000269|PubMed:12421919, ECO:0000269|PubMed:16682172}.;
- Pathway
- B cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);Inositol phosphate metabolism - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Fc Epsilon Receptor I Signaling in Mast Cells;Phosphatidylinositol Phosphate Metabolism;Joubert syndrome;EGF-Ncore;B Cell Receptor Signaling Pathway;IL-3 Signaling Pathway;Kit receptor signaling pathway;IL-4 Signaling Pathway;EGF-EGFR Signaling Pathway;D-<i>myo</i>-inositol (1,3,4)-trisphosphate biosynthesis;superpathway of D-<i>myo</i>-inositol (1,4,5)-trisphosphate metabolism;Signaling by Interleukins;Metabolism of lipids;Cytokine Signaling in Immune system;Downstream TCR signaling;TCR signaling;1D-<i>myo</i>-inositol hexakisphosphate biosynthesis II (mammalian);3-phosphoinositide degradation;TCR;Immune System;Metabolism;Interleukin receptor SHC signaling;Interleukin-2 family signaling;Adaptive Immune System;superpathway of inositol phosphate compounds;KitReceptor;Synthesis of IP3 and IP4 in the cytosol;PECAM1 interactions;CXCR4-mediated signaling events;Cell surface interactions at the vascular wall;Hemostasis;BCR signaling pathway;Inositol phosphate metabolism;IL3;Synthesis of PIPs at the plasma membrane;Class I PI3K signaling events;PI Metabolism;IL4;EPO signaling pathway;Phospholipid metabolism;GMCSF-mediated signaling events;Insulin Pathway;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Fc-epsilon receptor I signaling in mast cells;IL4-mediated signaling events;TCR signaling in naïve CD4+ T cells;IL3-mediated signaling events;Interleukin-3, 5 and GM-CSF signaling
(Consensus)
Recessive Scores
- pRec
- 0.105
Haploinsufficiency Scores
- pHI
- hipred
- Y
- hipred_score
- 0.790
- ghis
- 0.446
Essentials
- essential_gene_CRISPR
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.961
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Inpp5d
- Phenotype
- immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); neoplasm; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype;
Gene ontology
- Biological process
- phosphatidylinositol biosynthetic process;phosphate-containing compound metabolic process;apoptotic process;signal transduction;determination of adult lifespan;negative regulation of signal transduction;immunoglobulin mediated immune response;cytokine-mediated signaling pathway;negative regulation of B cell proliferation;intracellular signal transduction;positive regulation of apoptotic process;inositol phosphate metabolic process;negative regulation of interleukin-6 biosynthetic process;positive regulation of B cell differentiation;positive regulation of erythrocyte differentiation;negative regulation of monocyte differentiation;negative regulation of neutrophil differentiation;negative regulation of osteoclast differentiation;negative regulation of bone resorption;phosphatidylinositol dephosphorylation;negative regulation of immune response;T cell receptor signaling pathway;leukocyte migration
- Cellular component
- cytosol;cytoskeleton;plasma membrane;membrane raft
- Molecular function
- inositol-polyphosphate 5-phosphatase activity;protein binding;phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity;SH3 domain binding;phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity;inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity