INPP5K
inositol polyphosphate-5-phosphatase K, the group of Phosphoinositide phosphatases
Basic information
Region (hg38): 17:1494577-1516742
Links
Phenotypes
GenCC
Source:
- congenital muscular dystrophy with cataracts and intellectual disability (Strong), mode of inheritance: AR
- congenital muscular dystrophy with cataracts and intellectual disability (Strong), mode of inheritance: AR
- Marinesco-Sjogren syndrome (Supportive), mode of inheritance: AR
- congenital muscular dystrophy with cataracts and intellectual disability (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Muscular dystrophy, congenital, with cataracts and intellectual disability | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Musculoskeletal; Neurologic; Ophthalmologic | 28190456; 28190459 |
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn_genetic_diseases (65 variants)
- not_provided (50 variants)
- Congenital_muscular_dystrophy_with_cataracts_and_intellectual_disability (27 variants)
- INPP5K-related_disorder (10 variants)
- Muscular_dystrophy-dystroglycanopathy_(congenital_with_intellectual_disability),_type_B1 (2 variants)
- Congenital_myopathy (1 variants)
- not_specified (1 variants)
- Precursor_Cell_Lymphoblastic_Leukemia-Lymphoma (1 variants)
- Distal_myopathy (1 variants)
- Congenital_muscular_dystrophy (1 variants)
- See_cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the INPP5K gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016532.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 20 | 29 | ||||
| missense | 69 | 92 | ||||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 3 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 7 | 6 | 72 | 29 | 12 |
Highest pathogenic variant AF is 0.000014251
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| INPP5K | protein_coding | protein_coding | ENST00000421807 | 12 | 22318 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0000423 | 0.992 | 125724 | 0 | 24 | 125748 | 0.0000954 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.601 | 248 | 276 | 0.898 | 0.0000166 | 2953 |
| Missense in Polyphen | 88 | 108.67 | 0.8098 | 1255 | ||
| Synonymous | 0.469 | 113 | 120 | 0.945 | 0.00000803 | 848 |
| Loss of Function | 2.34 | 11 | 23.1 | 0.475 | 0.00000107 | 260 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000264 | 0.000264 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.000139 | 0.000139 |
| European (Non-Finnish) | 0.0000796 | 0.0000791 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.000131 | 0.000131 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Inositol 5-phosphatase which acts on inositol 1,4,5- trisphosphate, inositol 1,3,4,5-tetrakisphosphate, phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. Has 6-fold higher affinity for phosphatidylinositol 4,5-bisphosphate than for inositol 1,4,5- trisphosphate (PubMed:10753883). Negatively regulates assembly of the actin cytoskeleton. Controls insulin-dependent glucose uptake among inositol 3,4,5-trisphosphate phosphatases; therefore, is the specific regulator for insulin signaling in skeletal muscle (By similarity). {ECO:0000250|UniProtKB:Q8C5L6, ECO:0000269|PubMed:10753883, ECO:0000269|PubMed:28190456, ECO:0000269|PubMed:28190459}.;
- Pathway
- Inositol phosphate metabolism - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Notch Signaling Pathway;Notch Signaling Pathway;D-<i>myo</i>-inositol (1,3,4)-trisphosphate biosynthesis;superpathway of D-<i>myo</i>-inositol (1,4,5)-trisphosphate metabolism;Metabolism of lipids;1D-<i>myo</i>-inositol hexakisphosphate biosynthesis II (mammalian);3-phosphoinositide degradation;D-<i>myo</i>-inositol (1,4,5)-trisphosphate degradation;Metabolism;superpathway of inositol phosphate compounds;Phosphatidylinositol phosphate metabolism;Synthesis of PIPs at the plasma membrane;PI Metabolism;Phospholipid metabolism
(Consensus)
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- loftool
- 0.0696
- rvis_EVS
- -0.07
- rvis_percentile_EVS
- 48.78
Haploinsufficiency Scores
- pHI
- hipred
- Y
- hipred_score
- 0.589
- ghis
- 0.444
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.957
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Inpp5k
- 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); muscle phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- inpp5ka
- Affected structure
- skeletal muscle
- Phenotype tag
- abnormal
- Phenotype quality
- structure
Gene ontology
- Biological process
- negative regulation of protein phosphorylation;regulation of glycogen biosynthetic process;negative regulation of protein kinase activity;phosphatidylinositol biosynthetic process;G protein-coupled receptor signaling pathway;negative regulation of peptidyl-threonine phosphorylation;negative regulation of glucose transmembrane transport;dephosphorylation;actin cytoskeleton organization;cellular response to insulin stimulus;cellular response to hormone stimulus;negative regulation of peptidyl-serine phosphorylation;negative regulation of dephosphorylation;positive regulation of urine volume;glucose homeostasis;negative regulation of MAP kinase activity;negative regulation by host of viral transcription;negative regulation of glycogen biosynthetic process;negative regulation of single stranded viral RNA replication via double stranded DNA intermediate;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;negative regulation of insulin receptor signaling pathway;inositol phosphate dephosphorylation;phosphatidylinositol dephosphorylation;negative regulation of stress fiber assembly;negative regulation of protein kinase B signaling;negative regulation of calcium ion transport;cellular response to cAMP;cellular response to tumor necrosis factor;cellular response to epidermal growth factor stimulus;protein localization to plasma membrane;negative regulation of protein targeting to membrane;ruffle assembly;negative regulation of glycogen (starch) synthase activity;positive regulation of renal water transport
- Cellular component
- ruffle;nucleus;cytoplasm;endoplasmic reticulum;trans-Golgi network;cytosol;plasma membrane;membrane;ruffle membrane;neuron projection;perinuclear region of cytoplasm
- Molecular function
- phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity;inositol-polyphosphate 5-phosphatase activity;vasopressin receptor activity;protein binding;inositol bisphosphate phosphatase activity;phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity;phosphatidylinositol trisphosphate phosphatase activity;phosphatidylinositol phosphate 5-phosphatase activity;lipid phosphatase activity;inositol trisphosphate phosphatase activity;inositol-1,4,5-trisphosphate 5-phosphatase activity;inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity