INPP5K

Summary

INPP5K (inositol polyphosphate-5-phosphatase K, HGNC:33882) is a protein-coding gene on chromosome 17p13.3, encoding Inositol polyphosphate 5-phosphatase K (Q9BT40). 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.

This gene encodes a protein with 5-phosphatase activity toward polyphosphate inositol. The protein localizes to the cytosol in regions lacking actin stress fibers. It is thought that this protein may negatively regulate the actin cytoskeleton. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 51763 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital muscular dystrophy with cataracts and intellectual disability (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 176 total — 10 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 27
• MANE Select transcript: NM_016532

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33882
Approved symbol	INPP5K
Name	inositol polyphosphate-5-phosphatase K
Location	17p13.3
Locus type	gene with protein product
Status	Approved
Aliases	SKIP
Ensembl gene	ENSG00000132376
Ensembl biotype	protein_coding
OMIM	607875
Entrez	51763

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 16 protein_coding, 6 retained_intron, 5 nonsense_mediated_decay

ENST00000320345, ENST00000350761, ENST00000406424, ENST00000421807, ENST00000445774, ENST00000449479, ENST00000460733, ENST00000461552, ENST00000477115, ENST00000477910, ENST00000481867, ENST00000487039, ENST00000495339, ENST00000498390, ENST00000571274, ENST00000573790, ENST00000574561, ENST00000574955, ENST00000575172, ENST00000576646, ENST00000898971, ENST00000898972, ENST00000898973, ENST00000898974, ENST00000923268, ENST00000966406, ENST00000966407

RefSeq mRNA: 3 — MANE Select: NM_016532 NM_001135642, NM_016532, NM_130766

CCDS: CCDS11004, CCDS11005

Canonical transcript exons

ENST00000421807 — 12 exons

Exon	Start	End
ENSE00001198955	1494577	1495879
ENSE00001825544	1516456	1516612
ENSE00003517234	1496666	1496803
ENSE00003524267	1496060	1496164
ENSE00003537890	1496319	1496402
ENSE00003579231	1513453	1513561
ENSE00003614569	1508115	1508226
ENSE00003637578	1513872	1513979
ENSE00003644642	1506980	1507089
ENSE00003684224	1509178	1509353
ENSE00003785832	1497936	1498122
ENSE00003790640	1509683	1509799

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 98.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.7275 / max 490.8687, expressed in 1819 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163721	12.9225	1805
163723	5.2231	1744
163722	3.6185	1608
163724	2.5964	1493
163725	0.8491	526
163726	0.3049	126
163718	0.1813	69
163727	0.0150	4
163719	0.0137	1
163720	0.0029	1

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	98.04	gold quality
right lung	UBERON:0002167	96.42	gold quality
right lobe of thyroid gland	UBERON:0001119	96.25	gold quality
left lobe of thyroid gland	UBERON:0001120	96.10	gold quality
apex of heart	UBERON:0002098	95.96	gold quality
granulocyte	CL:0000094	95.30	gold quality
thyroid gland	UBERON:0002046	94.82	gold quality
skin of leg	UBERON:0001511	94.62	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.54	gold quality
lower esophagus	UBERON:0013473	94.51	gold quality
upper lobe of left lung	UBERON:0008952	94.48	gold quality
omental fat pad	UBERON:0010414	94.33	gold quality
peritoneum	UBERON:0002358	94.28	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.26	gold quality
mucosa of stomach	UBERON:0001199	94.16	gold quality
skin of abdomen	UBERON:0001416	94.10	gold quality
tibial nerve	UBERON:0001323	94.02	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.70	gold quality
monocyte	CL:0000576	93.62	gold quality
popliteal artery	UBERON:0002250	93.53	gold quality
tibial artery	UBERON:0007610	93.52	gold quality
leukocyte	CL:0000738	93.41	gold quality
left coronary artery	UBERON:0001626	93.40	gold quality
right coronary artery	UBERON:0001625	93.35	gold quality
mononuclear cell	CL:0000842	93.34	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.31	gold quality
gastrocnemius	UBERON:0001388	93.28	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.22	gold quality
ectocervix	UBERON:0012249	93.22	gold quality
aorta	UBERON:0000947	93.17	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	17.05
E-MTAB-6379	no	918.78
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
AQP2	Activation
AVP	Repression
AVPR2	Activation

Upstream regulators (CollecTRI, top): MYOD1

miRNA regulators (miRDB)

50 targeting INPP5K, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-2117	98.48	67.97	1307
HSA-MIR-6837-3P	98.42	66.71	1149
HSA-MIR-4691-5P	98.41	66.77	1343

Literature-anchored findings (GeneRIF, showing 17)

• identification of novel domain that mediates membrane ruffle localization (PMID:12536145)
• The authors report that HBV core protein interacts with a cellular SKIP (skeletal muscle and kidney enriched inositol phosphatase) protein, an endoplasmic reticulum-located phosphoinositide 5-phosphatase, both in vivo and in vitro. (PMID:18774950)
• Specific suppression of insulin signaling is achieved via the spatiotemporal regulation of SKIP through the scaffolding function of Pak1. (PMID:22751929)
• SKIP controls the IGF-II-PI 3-kinase-Akt-mTOR auto-regulation loop during myogenesis. (PMID:22815484)
• Study reveals that SKIP is a significant regulator of glioblastoma cell migration and that increased expression of SKIP may confer a survival advantage. (PMID:25241900)
• These findings suggest a model by which GRP78 regulates intracellular localization of SKIP and how SKIP binds to Pak1 on insulin stimulation. (PMID:26940976)
• In individuals exhibiting congenital muscular dystrophy, early-onset cataracts, and mild intellectual disability but normal cranial magnetic resonance imaging, we identified bi-allelic mutations in INPP5K, encoding inositol polyphosphate-5-phosphatase K. (PMID:28190456)
• Mutations in INPP5K cause a congenital muscular dystrophy syndrome with short stature, cataracts, and intellectual disability. (PMID:28190459)
• our findings further support the essential role of INPP5K in the lens and skeletal muscle development in humans and zebrafish. (PMID:28940338)
• the distribution of genotype frequency exhibited no significant differences between the Parkinson’s disease and control groups (P > 0.025) in INPP5K rs1109303 (P = 0.048, OR = 0.806, 95%CI = 0.650 - 0.998). (PMID:29607885)
• focused on the two genes CRK and INPP5K, which were regulated by rs1109303 in the occipital cortex and anterior cingulate cortex BA24, respectively (PMID:30225765)
• Phosphoinositide 5-phosphatases SKIP and SHIP2 in ruffles, the endoplasmic reticulum and the nucleus: An update. (PMID:31628071)
• The Prediction and Prognostic Significance of INPP5K Expression in Patients with Liver Cancer. (PMID:32420386)
• The phosphoinositide 5-phosphatase INPP5K: From gene structure to in vivo functions. (PMID:33060052)
• INPP5K and SIL1 associated pathologies with overlapping clinical phenotypes converge through dysregulation of PHGDH. (PMID:33792664)
• INPP5K and Atlastin-1 maintain the nonuniform distribution of ER-plasma membrane contacts in neurons. (PMID:34556534)
• INPP5K controls the dynamic structure and signaling of wild-type and mutated, leukemia-associated IL-7 receptors. (PMID:36599086)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	inpp5kb	ENSDARG00000078618
danio_rerio	inpp5ka	ENSDARG00000099563
mus_musculus	Inpp5k	ENSMUSG00000006127
rattus_norvegicus	Inpp5k	ENSRNOG00000056954
drosophila_melanogaster	CG9784	FBGN0030761
drosophila_melanogaster	CG6805	FBGN0034179
drosophila_melanogaster	Synj	FBGN0034691
drosophila_melanogaster	sp3	FBGN0038890
caenorhabditis_elegans		WBGENE00006763
caenorhabditis_elegans	sac-2	WBGENE00012353

Paralogs (13): SYNJ2 (ENSG00000078269), FIG4 (ENSG00000112367), OCRL (ENSG00000122126), INPP5E (ENSG00000148384), SYNJ1 (ENSG00000159082), INPPL1 (ENSG00000165458), INPP5D (ENSG00000168918), SH2D1A (ENSG00000183918), INPP5J (ENSG00000185133), SH2D1B (ENSG00000198574), INPP5F (ENSG00000198825), INPP5B (ENSG00000204084), SACM1L (ENSG00000211456)

Protein

Protein identifiers

Inositol polyphosphate 5-phosphatase K — Q9BT40 (reviewed: Q9BT40)

Alternative names: Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase, Phosphatidylinositol-4,5-bisphosphate 5-phosphatase, Skeletal muscle and kidney-enriched inositol phosphatase

All UniProt accessions (12): Q9BT40, C9JQW8, C9JZB0, I3L0Y0, I3L1R1, I3L2L1, I3L4A5, I3NI31, J3KN07, K7EMS8, K7ENF7, K7EPG6

UniProt curated annotations — full annotation on UniProt →

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. 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.

Subunit / interactions. Interacts with GPR78; necessary for INPP5K localization at the endoplasmic reticulum. Interacts with PAK1; competes with GPR78.

Subcellular location. Endoplasmic reticulum. Cytoplasm.

Tissue specificity. Ubiquitously expressed with highest levels in skeletal muscle, heart and kidney.

Disease relevance. Muscular dystrophy, congenital, with cataracts and impaired intellectual development (MDCCAID) [MIM:617404] An autosomal recessive form of muscular dystrophy with onset in early childhood and characterized by progressive muscle weakness. Almost all patients also have early-onset cataracts and intellectual disability of varying severity. Some patients have seizures. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type II family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BT40-1	1	yes
Q9BT40-2	2

RefSeq proteins (3): NP_001129114, NP_057616, NP_570122 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000300	IPPc	Domain
IPR036691	Endo/exonu/phosph_ase_sf	Homologous_superfamily
IPR041611	SKICH	Domain
IPR046985	IP5	Family

Pfam: PF17751, PF22669

Enzyme classification (BRENDA):

• EC 3.1.3.56 — inositol-polyphosphate 5-phosphatase (BRENDA: 35 organisms, 62 substrates, 55 inhibitors, 44 Km, 15 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-MYO-INOSITOL 1,4,5-TRISPHOSPHATE	0.001–0.32	19
5-DIPHOSPHOINOSITOL 1,2,3,4,6-PENTAKISPHOSPHATE	0.007–0.0481	11
D-MYO-INOSITOL 1,3,4,5-TETRAKISPHOSPHATE	0.0008–0.019	7
1,5-BISDIPHOSPHOINOSITOL 2,3,4,6-TETRAKISPHOSPHA	0.0101	1
5-DIPHOSPHOINOSITOL 1,3,4,6-TETRAKISPHOSPHATE	0.0568	1
7-METHYL-6-THIOGUANOSINE	0.056	1

Catalyzed reactions (Rhea), 5 shown:

• 1D-myo-inositol 1,3,4,5-tetrakisphosphate + H2O = 1D-myo-inositol 1,3,4-trisphosphate + phosphate (RHEA:11392)
• 1D-myo-inositol 1,4,5-trisphosphate + H2O = 1D-myo-inositol 1,4-bisphosphate + phosphate (RHEA:19797)
• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) + phosphate (RHEA:22764)
• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) + phosphate (RHEA:25528)
• 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) + phosphate (RHEA:43548)

UniProt features (22 total): sequence variant 9, mutagenesis site 5, region of interest 3, sequence conflict 3, chain 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
22MJ	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BT40-F1	88.97	0.74

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (5):

Position	Phenotype
310	no phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity.
349	no effect on egf-induced ruffle localization.
361	significant decrease in egf-induced ruffle localization.
362	significant decrease in egf-induced ruffle localization.
376	no effect on egf-induced ruffle localization.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-1430728	Metabolism
R-HSA-1483255	PI Metabolism
R-HSA-1483257	Phospholipid metabolism
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 382 (showing top): GOBP_LIPID_MODIFICATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_PHOSPHOLIPID_DEPHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_PROTEIN_TARGETING

GO Biological Process (35): in utero embryonic development (GO:0001701), regulation of glycogen biosynthetic process (GO:0005979), phosphatidylinositol biosynthetic process (GO:0006661), G protein-coupled receptor signaling pathway (GO:0007186), negative regulation of D-glucose transmembrane transport (GO:0010829), actin cytoskeleton organization (GO:0030036), cellular response to insulin stimulus (GO:0032869), cellular response to hormone stimulus (GO:0032870), negative regulation of dephosphorylation (GO:0035305), positive regulation of urine volume (GO:0035810), glucose homeostasis (GO:0042593), host-mediated suppression of viral transcription (GO:0043922), negative regulation of glycogen biosynthetic process (GO:0045719), negative regulation of single stranded viral RNA replication via double stranded DNA intermediate (GO:0045869), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), negative regulation of insulin receptor signaling pathway (GO:0046627), phosphatidylinositol dephosphorylation (GO:0046856), negative regulation of stress fiber assembly (GO:0051497), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), negative regulation of calcium ion transport (GO:0051926), cellular response to cAMP (GO:0071320), cellular response to tumor necrosis factor (GO:0071356), cellular response to epidermal growth factor stimulus (GO:0071364), protein localization to plasma membrane (GO:0072659), negative regulation of protein targeting to membrane (GO:0090315), ruffle assembly (GO:0097178), positive regulation of renal water transport (GO:2001153), lipid metabolic process (GO:0006629), phospholipid metabolic process (GO:0006644), response to insulin (GO:0032868), glycerolipid metabolic process (GO:0046486), regulation of transport (GO:0051049), cellular response to oxygen-containing compound (GO:1901701), negative regulation of RNA biosynthetic process (GO:1902679)

GO Molecular Function (14): phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity (GO:0004439), vasopressin receptor activity (GO:0005000), inositol bisphosphate phosphatase activity (GO:0016312), phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity (GO:0034485), phosphatidylinositol trisphosphate phosphatase activity (GO:0034594), phosphatidylinositol phosphate 5-phosphatase activity (GO:0034595), lipid phosphatase activity (GO:0042577), inositol trisphosphate phosphatase activity (GO:0046030), inositol-1,4,5-trisphosphate 5-phosphatase activity (GO:0052658), inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity (GO:0052659), inositol-polyphosphate 5-phosphatase activity (GO:0004445), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791)

GO Cellular Component (11): ruffle (GO:0001726), nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), trans-Golgi network (GO:0005802), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), ruffle membrane (GO:0032587), neuron projection (GO:0043005), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
PI Metabolism	1
Phospholipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
glycogen biosynthetic process	2
phosphatidylinositol metabolic process	2
negative regulation of RNA biosynthetic process	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
phosphatidylinositol phosphate 5-phosphatase activity	2
inositol phosphate phosphatase activity	2
phosphatidylinositol phosphate phosphatase activity	2
inositol-polyphosphate 5-phosphatase activity	2
plasma membrane bounded cell projection	2
intracellular membrane-bounded organelle	2
chordate embryonic development	1
regulation of glucan biosynthetic process	1
regulation of glycogen metabolic process	1
biosynthetic process	1
G protein-coupled receptor activity	1
signal transduction	1
regulation of D-glucose transmembrane transport	1
negative regulation of transmembrane transport	1
D-glucose transmembrane transport	1
cytoskeleton organization	1
actin filament-based process	1
response to insulin	1
cellular response to peptide hormone stimulus	1
response to hormone	1
cellular response to chemical stimulus	1
cellular response to endogenous stimulus	1
dephosphorylation	1
regulation of dephosphorylation	1
negative regulation of phosphate metabolic process	1
regulation of urine volume	1
carbohydrate homeostasis	1
host-mediated perturbation of viral transcription	1
host-mediated suppression of viral proces	1
regulation of glycogen biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
negative regulation of glycogen metabolic process	1
single stranded viral RNA replication via double stranded DNA intermediate	1

Protein interactions and networks

STRING

1106 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INPP5K	INPP5A	Q14642	582
INPP5K	ARHGAP1	Q07960	523
INPP5K	INPP4A	Q96PE3	490
INPP5K	PHYKPL	Q8IUZ5	474
INPP5K	KDSR	Q06136	462
INPP5K	SCIN	Q9Y6U3	458
INPP5K	ARL8B	Q9NVJ2	448
INPP5K	INPP4B	O15327	436
INPP5K	GSN	P06396	434
INPP5K	RAC1	P15154	431
INPP5K	AP2A1	O95782	426
INPP5K	GULP1	Q9UBP9	425
INPP5K	ZFHX2	Q9C0A1	424
INPP5K	ARFIP2	P53365	423
INPP5K	AKT1	P31749	422

IntAct

100 interactions, top by confidence:

A	B	Type	Score
MAD2L1BP	INPP5K	psi-mi:“MI:0915”(physical association)	0.870
INPP5K	MAD2L1BP	psi-mi:“MI:0915”(physical association)	0.870
KRT31	INPP5K	psi-mi:“MI:0915”(physical association)	0.780
INPP5K	FATE1	psi-mi:“MI:0915”(physical association)	0.780
INPP5K	KRT31	psi-mi:“MI:0915”(physical association)	0.780
FATE1	INPP5K	psi-mi:“MI:0915”(physical association)	0.780
ARL6IP1	INPP5K	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
INPP5K	GART	psi-mi:“MI:0914”(association)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
FADS6	INPP5K	psi-mi:“MI:0915”(physical association)	0.560
INPP5K	GOLT1B	psi-mi:“MI:0915”(physical association)	0.560
SFT2D2	INPP5K	psi-mi:“MI:0915”(physical association)	0.560
INPP5K	TNFRSF10D	psi-mi:“MI:0915”(physical association)	0.560
ATP5PF	INPP5K	psi-mi:“MI:0915”(physical association)	0.560
PBX3	INPP5K	psi-mi:“MI:0915”(physical association)	0.560
INPP5K	KLK6	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (94): INPP5K (Two-hybrid), INPP5K (Two-hybrid), FATE1 (Two-hybrid), INPP5K (Affinity Capture-RNA), INPP5K (Affinity Capture-RNA), INPP5K (Affinity Capture-MS), INPP5K (Affinity Capture-MS), INPP5K (Affinity Capture-MS), INPP5K (Two-hybrid), INPP5K (Two-hybrid), MAD2L1BP (Affinity Capture-MS), KATNA1 (Affinity Capture-MS), USP47 (Affinity Capture-MS), RFX1 (Affinity Capture-MS), UBB (Affinity Capture-MS)

ESM2 similar proteins: A0JN54, A1ZAW0, A8XP91, B4JT42, D3ZGS3, G5ECL2, O15056, O17907, O18964, O35646, O43001, O43426, O55207, O62471, O74369, O76745, O88501, O88673, P16885, P20192, P23743, P32019, P34370, P40384, P41888, P51556, P56523, Q01968, Q08227, Q09315, Q0J954, Q22036, Q24239, Q5EAF2, Q62910, Q6DNF3, Q6NVF0, Q7XR46, Q8C5L6, Q8CHC4

Diamond homologs: A0A8I3NFE2, A8MR21, D3ZGS3, D7PF45, G5ECL2, O14306, O15056, O15357, O18964, O43001, O43426, O55207, P32019, P40559, P50942, P59644, P97573, Q01968, Q08227, Q0WQ41, Q0WT19, Q12271, Q15735, Q2I6J0, Q2I6J1, Q5U2Z7, Q62910, Q66GQ6, Q6NVF0, Q6P4S2, Q6P549, Q7Z5H3, Q84MA2, Q8BL80, Q8C4V1, Q8C5L6, Q8CHC4, Q8GTS0, Q8H0Z6, Q8K337

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

176 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	4
Uncertain significance	83
Likely benign	30
Benign	16

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
1703618	GRCh37/hg19 17p13.3(chr17:525-1464281)	Pathogenic
1710311	NM_016532.4(INPP5K):c.165G>T (p.Leu55Phe)	Pathogenic
1710312	NM_016532.4(INPP5K):c.753_756del (p.Arg251fs)	Pathogenic
4075912	GRCh37/hg19 17p13.3(chr17:1407876-1414210)x1	Pathogenic
417778	NM_016532.4(INPP5K):c.899A>G (p.Tyr300Cys)	Pathogenic
417779	NM_016532.4(INPP5K):c.277A>G (p.Met93Val)	Pathogenic
417780	NM_016532.4(INPP5K):c.67G>A (p.Val23Met)	Pathogenic
417781	NM_016532.4(INPP5K):c.805G>A (p.Asp269Asn)	Pathogenic
417782	NM_016532.4(INPP5K):c.1251_1252del (p.Asn417fs)	Pathogenic
523260	GRCh37/hg19 17p13.3(chr17:1361431-2573023)	Pathogenic
1708251	NM_016532.4(INPP5K):c.653G>A (p.Trp218Ter)	Likely pathogenic
1708252	NM_016532.4(INPP5K):c.925A>G (p.Ser309Gly)	Likely pathogenic
2227818	NM_016532.4(INPP5K):c.1229_1230del (p.Phe410fs)	Likely pathogenic
417783	NM_016532.4(INPP5K):c.418G>A (p.Gly140Ser)	Likely pathogenic

SpliceAI

2248 predictions. Top by Δscore:

Variant	Effect	Δscore
17:1496055:CTTA:C	donor_loss	1.0000
17:1496057:TA:T	donor_loss	1.0000
17:1496058:A:AC	donor_gain	1.0000
17:1496058:ACC:A	donor_loss	1.0000
17:1496059:C:CA	donor_loss	1.0000
17:1496059:C:CC	donor_gain	1.0000
17:1496162:AAC:A	acceptor_gain	1.0000
17:1496165:C:CA	acceptor_loss	1.0000
17:1496165:C:CC	acceptor_gain	1.0000
17:1496166:T:A	acceptor_loss	1.0000
17:1496314:CGTA:C	donor_loss	1.0000
17:1496318:C:CA	donor_loss	1.0000
17:1496398:CCCAC:C	acceptor_gain	1.0000
17:1496399:CCACC:C	acceptor_gain	1.0000
17:1496403:C:A	acceptor_loss	1.0000
17:1496404:T:A	acceptor_loss	1.0000
17:1496644:T:TA	donor_gain	1.0000
17:1496804:C:CC	acceptor_gain	1.0000
17:1497937:T:TA	donor_gain	1.0000
17:1498123:C:CC	acceptor_gain	1.0000
17:1509176:A:AC	donor_gain	1.0000
17:1509177:C:CC	donor_gain	1.0000
17:1509177:CT:C	donor_gain	1.0000
17:1509214:CAATT:C	donor_gain	1.0000
17:1509353:CCTGG:C	acceptor_gain	1.0000
17:1496160:TAAAC:T	acceptor_gain	0.9900
17:1496161:AAAC:A	acceptor_gain	0.9900
17:1496163:AC:A	acceptor_gain	0.9900
17:1496164:CC:C	acceptor_gain	0.9900
17:1496399:CCAC:C	acceptor_gain	0.9900

AlphaMissense

2979 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:1498090:C:G	R270P	0.999
17:1498100:A:G	W267R	0.999
17:1498100:A:T	W267R	0.999
17:1508199:G:C	N194K	0.999
17:1508199:G:T	N194K	0.999
17:1497958:A:T	V314D	0.998
17:1497968:G:C	H311D	0.998
17:1497972:G:C	S309R	0.998
17:1497972:G:T	S309R	0.998
17:1497974:T:G	S309R	0.998
17:1498091:G:T	R270S	0.998
17:1508206:T:A	D192V	0.998
17:1508206:T:C	D192G	0.998
17:1508206:T:G	D192A	0.998
17:1508209:C:A	G191V	0.998
17:1508209:C:T	G191E	0.998
17:1513963:A:G	W21R	0.998
17:1513963:A:T	W21R	0.998
17:1497961:G:T	P313H	0.997
17:1497966:G:C	H311Q	0.997
17:1497966:G:T	H311Q	0.997
17:1498098:C:A	W267C	0.997
17:1498098:C:G	W267C	0.997
17:1507022:G:T	P245H	0.997
17:1508196:A:C	F195L	0.997
17:1508196:A:T	F195L	0.997
17:1508198:A:G	F195L	0.997
17:1508205:G:C	D192E	0.997
17:1508205:G:T	D192E	0.997
17:1508207:C:G	D192H	0.997

dbSNP variants (sampled 300 via entrez): RS1000146033 (17:1499915 C>G,T), RS1000176871 (17:1499627 C>T), RS1000189222 (17:1503802 C>T), RS1000437017 (17:1508644 G>C), RS1000463430 (17:1515049 G>A), RS1000509545 (17:1498599 T>A), RS1000582848 (17:1495690 C>G), RS1000629066 (17:1503729 A>C), RS1000645814 (17:1509108 C>T), RS1000661201 (17:1502332 G>C), RS1000664998 (17:1503972 A>G), RS1000730424 (17:1503573 A>G), RS1000771551 (17:1507454 G>A), RS1001229721 (17:1515135 G>T), RS1001316367 (17:1511570 A>G)

Disease associations

OMIM: gene MIM:607875 | disease phenotypes: MIM:617404, MIM:247200, MIM:160500, MIM:613155, MIM:117000, MIM:607432

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital muscular dystrophy with cataracts and intellectual disability	Strong	Autosomal recessive
Marinesco-Sjogren syndrome	Supportive	Autosomal recessive

Mondo (8): congenital muscular dystrophy with cataracts and intellectual disability (MONDO:0024607), Miller-Dieker lissencephaly syndrome (MONDO:0009532), distal myopathy (MONDO:0018949), muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 (MONDO:0013159), congenital muscular dystrophy (MONDO:0019950), congenital myopathy (MONDO:0019952), lissencephaly spectrum disorders (MONDO:0018838), Marinesco-Sjogren syndrome (MONDO:0009567)

Orphanet (6): Congenital muscular dystrophy-cataract-intellectual disability syndrome (Orphanet:662184), Miller-Dieker syndrome (Orphanet:531), Distal myopathy (Orphanet:599), Congenital muscular dystrophy (Orphanet:97242), Congenital myopathy (Orphanet:97245), Lissencephaly (Orphanet:48471)

HPO phenotypes

27 total (28 of 27 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000486	Strabismus
HP:0000518	Cataract
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001288	Gait disturbance
HP:0002061	Lower limb spasticity
HP:0002093	Respiratory insufficiency
HP:0002650	Scoliosis
HP:0002808	Kyphosis
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003306	Spinal rigidity
HP:0003307	Hyperlordosis
HP:0003391	Gowers sign
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003676	Progressive
HP:0003701	Proximal muscle weakness
HP:0004322	Short stature
HP:0007126	Proximal amyotrophy
HP:0009126	Increased adipose tissue
HP:0011463	Childhood onset
HP:0030051	Tip-toe gait
HP:0001339	Lissencephaly

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004599_112	Mean platelet volume	2.000000e-09

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D054082	Lissencephaly	C10.500.507.450.499; C16.131.666.507.450.499

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Inositol polyphosphate phosphatases

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation	2
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
exemestane	increases expression	1
2-palmitoylglycerol	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Cadmium	decreases expression	1
Doxorubicin	decreases expression	1
Glucosamine	increases expression, decreases reaction	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Vitamin E	increases expression	1
Cadmium Chloride	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1UK	Abcam HeLa INPP5K KO	Cancer cell line	Female
CVCL_D7SB	Ubigene A-549 INPP5K KO	Cancer cell line	Male
CVCL_SS72	HAP1 INPP5K (-) 1	Cancer cell line	Male
CVCL_SS73	HAP1 INPP5K (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

50 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02887365	PHASE4	UNKNOWN	A Phase II Study of Tegafur-Uracil as Maintenance Chemotherapy in Patients With Stage II of Colon Cancer
NCT01422200	PHASE4	COMPLETED	Flu Vaccine Study in Neuromuscular Patients 2011
NCT07549399	PHASE3	NOT_YET_RECRUITING	SCRT + Chemo Targeted Immuno-neoadjuvant Therapy for High-risk pMMR/MSS RC
NCT07551479	PHASE3	NOT_YET_RECRUITING	SCRT Based iTNT vs. LCRT Based TNT for MSS Locally Advanced Rectal Cancer
NCT03271047	PHASE2	COMPLETED	Study of Binimetinib + Nivolumab Plus or Minus Ipilimumab in Patients With Previously Treated Microsatellite-stable (MSS) Metastatic Colorectal Cancer With RAS Mutation
NCT04030260	PHASE2	UNKNOWN	Regorafenib and PD-1 Antibody in Combination With Radiotherapy for pMMR/MSS Metastatic Colorectal Cancer
NCT04098068	PHASE2	COMPLETED	Study of MK-3475 (Pembrolizumab) in Patients With Microsatellite Unstable (MSI) Tumors (Cohort D)
NCT04483219	PHASE2	UNKNOWN	Tyrosine Kinase Inhibitor (TKI) + Anti-PD-1 Antibody in TKI-responded Microsatellite Stability/Proficient Mismatch Repair (MSS/pMMR) Metastatic Colorectal Adenocarcinoma.
NCT04527068	PHASE2	UNKNOWN	QL1101 in Combination With JS001 in Patients With pMMR/MSS Refractory Metastatic Colorectal Cancer
NCT04659382	PHASE2	UNKNOWN	Study to Evaluate Efficacy and Safety of Selective Internal Radiation Therapy Plus Xelox, Bevacizumab and Atezolizumab (Immune Chekpoint Inhibitor) in Patients With Liver-dominant Metastatic Colorectal Cancer
NCT05731726	PHASE2	RECRUITING	Serplulimab Combined With CAPEOX + Celecoxib as Neoadjuvant Treatment for Locally Advanced Rectal Cancer
NCT05733611	PHASE2	TERMINATED	RP2/RP3 in Combination With Atezolizumab and Bevacizumab for the Treatment of Patients With CRC
NCT05815303	PHASE2	UNKNOWN	XELOX Combined With Cadonilimab Versus XELOX as Neoadjuvant Treatment for Locally Advanced, pMMR Rectal Cancer
NCT05933980	PHASE2	UNKNOWN	Toripalimab,Celecoxib and Regorafenib in the Treatment of Refractory Advanced Colorectal Cancer
NCT05970302	PHASE2	RECRUITING	XELOX +Bev +Tislelizumab for First-line Treatment of MSS/pMMR RAS-mutated mCRC
NCT06321081	PHASE2	RECRUITING	ICE Study: Combination of Irinotecan Plus Cetuximab and Envafolimab as a Rechallenge Regimen in mCRC
NCT06415851	PHASE2	NOT_YET_RECRUITING	Chemotherapy Plus Bevacizumab and Anti-PD-1 Followed by Induction Therapy of Chemotherapy Plus Bevacizumab
NCT06593548	PHASE2	NOT_YET_RECRUITING	Lvosidenib (AK112) Combined With CapeOX and Radiotherapy in Patients With Unresectable Metastatic MSS-type Colorectal Cancer
NCT06850103	PHASE2	RECRUITING	SCRT-CAPEOX-Serplulimab for MSS/pMMR Rectal Cancer With Oligometastases
NCT06908031	PHASE2	RECRUITING	SCRT + mFOLFOX6 + PD-1 Antibody + Targeted Therapy for HIgh-Risk pMMR/MSS Rectal Cancer
NCT07156682	PHASE2	NOT_YET_RECRUITING	QL1706 Plus XELOX as Neoadjuvant Therapy for MSS/pMMR Clinical Stage III Colon Cancer
NCT07506109	PHASE2	RECRUITING	A Phase II Study of Sintilimab Combined With Ipilimumab N01, Cetuximab and Dabrafenib in Patients With Microsatellite-Stable, BRAF V600E-Mutated Metastatic Colorectal Cancer
NCT07527520	PHASE2	NOT_YET_RECRUITING	Neoadjuvant Moderately Hypofractionated Radiotherapy Combined With Chemotherapy and Immunotherapy for High-risk pMMR/MSS Locally Advanced Rectal Cancer: A Prospective, Multi-center Randomized Control Phase II Trial
NCT03274804	PHASE1	COMPLETED	Combined PD-1 and CCR5 Inhibition for the Treatment of Refractory Microsatellite Stable mCRC
NCT04046445	PHASE1	ACTIVE_NOT_RECRUITING	Phase 1b Study to Evaluate ATP128, VSV-GP128 and BI 754091, in Patients With Stage IV Colorectal Cancer
NCT07001592	PHASE1	RECRUITING	Intra-tumoral (IT) Injection of vvDD-hIL2-2-RG-1 for Metastatic Gastrointestinal and Peritoneal Tumors
NCT01805024	PHASE1	COMPLETED	Congenital Muscular Dystrophy Ascending Multiple Dose Cohort Study Analyzing Pharmacokinetics at Three Dose Levels In Children and Adolescents With Assessment of Safety and Tolerability of Omigapil (CALLISTO)
NCT01403402	Not specified	RECRUITING	Congenital Muscle Disease Study of Patient and Family Reported Medical Information
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT05877573	Not specified	RECRUITING	Toripalimab Combined With Neoadjuvant Chemoradiotherapy as First-line Treatment for Locally Advanced，High-Risk，MSS Rectal Cancer
NCT06199232	Not specified	ACTIVE_NOT_RECRUITING	Targeted Treatment Plus Tislelizumab and HAIC for Advanced CRCLM Failed From Standard Systemic Treatment
NCT06936488	Not specified	ENROLLING_BY_INVITATION	A Prospective, Single Arm, Open Label, Phase II Clinical Study on the Efficacy and Safety of Ivonescimab (AK112) Combined With TAS-102 in the Treatment of Refractory MSS/pMMR Advanced Colorectal Cancer
NCT07502989	Not specified	RECRUITING	Muscle Health Measurements Using Electrical Impedance Myography
NCT01836627	Not specified	COMPLETED	A Study to Test Lung Stretch Therapy (Hyperinsufflation) in Children With Collagen VI Muscular Dystrophy
NCT04001595	Not specified	UNKNOWN	Global FKRP Registry
NCT05102916	Not specified	RECRUITING	Swiss Registry for Neuromuscular Disorders
NCT05982119	Not specified	RECRUITING	Assessments in Patients With Muscular Pathology and in Control Subjects : The ActiLiège Next Study
NCT06529848	Not specified	RECRUITING	Impact of Exercise Training on Ischemia With Non-Obstructive Coronary Arteries (INOCA): The ExINOCA Study
NCT07138963	Not specified	RECRUITING	Phenotype - Genotype Correlation in a Sample of Egyptian Patients With Congenital Myopathies and Congenital Muscular Dystrophies
NCT02020187	Not specified	COMPLETED	Aerobic Training in Patients With Congenital Myopathies