INPP5K

inositol polyphosphate-5-phosphatase K, the group of Phosphoinositide phosphatases

Basic information

Region (hg38): 17:1494576-1516742

Links

ENSG00000132376 ∙ NCBI:51763 ∙ OMIM:607875 ∙ HGNC:33882 ∙ Uniprot:Q9BT40 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the INPP5K gene.

• Congenital muscular dystrophy with cataracts and intellectual disability (2 variants)
• not provided (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.

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				19	6	25
missense	2	2	33	4	6	47
nonsense		1				1
start loss						0
frameshift		1				1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			2	4		6
non coding				2	3	5
Total	2	4	34	25	15

Highest pathogenic variant AF is 0.00000657

Variants in INPP5K

This is a list of pathogenic ClinVar variants found in the INPP5K region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-1495873-G-A		Inborn genetic diseases	Uncertain significance (Nov 10, 2022)
17-1495875-G-A		Inborn genetic diseases	Uncertain significance (Dec 03, 2021)
17-1495877-G-A			Likely benign (Jul 01, 2022)
17-1496081-C-T			Benign (Dec 31, 2019)
17-1496097-CTG-C		Congenital muscular dystrophy with cataracts and intellectual disability	Pathogenic (Apr 04, 2017)
17-1496103-C-G		Congenital muscular dystrophy with cataracts and intellectual disability	Uncertain significance (Dec 03, 2021)
17-1496119-GAA-G		Inborn genetic diseases	Likely pathogenic (Oct 05, 2020)
17-1496135-G-A		INPP5K-related disorder	Benign/Likely benign (Nov 18, 2019)
17-1496140-G-C		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
17-1496145-T-C		Inborn genetic diseases	Uncertain significance (May 11, 2021)
17-1496310-G-C			Likely benign (May 24, 2018)
17-1496315-G-A		Inborn genetic diseases	Uncertain significance (Mar 14, 2024)
17-1496328-G-A			Benign (Dec 31, 2019)
17-1496352-G-A			Likely benign (May 21, 2018)
17-1496362-C-G			Uncertain significance (May 29, 2019)
17-1496364-G-A			Benign/Likely benign (Jul 01, 2024)
17-1496392-C-T		Inborn genetic diseases	Uncertain significance (Dec 19, 2020)
17-1496658-C-G			Likely benign (May 31, 2018)
17-1496690-C-T		INPP5K-related disorder	Likely benign (Apr 01, 2024)
17-1496691-G-A		Inborn genetic diseases	Uncertain significance (Jul 13, 2021)
17-1496746-C-T		Inborn genetic diseases	Likely benign (Dec 08, 2023)
17-1496811-C-T			Likely benign (Apr 24, 2018)
17-1497939-C-T		INPP5K-related disorder	Likely benign (Jun 08, 2023)
17-1497969-G-A			Likely benign (May 03, 2018)
17-1497972-G-A			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

• 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