INPP5D

Summary

INPP5D (inositol polyphosphate-5-phosphatase D, HGNC:6079) is a protein-coding gene on chromosome 2q37.1, encoding Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (Q92835). 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.

This gene is a member of the inositol polyphosphate-5-phosphatase (INPP5) family and encodes a protein with an N-terminal SH2 domain, an inositol phosphatase domain, and two C-terminal protein interaction domains. Expression of this protein is restricted to hematopoietic cells where its movement from the cytosol to the plasma membrane is mediated by tyrosine phosphorylation. At the plasma membrane, the protein hydrolyzes the 5’ phosphate from phosphatidylinositol (3,4,5)-trisphosphate and inositol-1,3,4,5-tetrakisphosphate, thereby affecting multiple signaling pathways. The protein is also partly localized to the nucleus, where it may be involved in nuclear inositol phosphate signaling processes. Overall, the protein functions as a negative regulator of myeloid cell proliferation and survival. Mutations in this gene are associated with defects and cancers of the immune system. Deficiencies in the encoded protein, SHIP1, have been associated with Inflammatory Bowel Disease types such as Crohn’s Disease and Ulcerative Colitis. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 3635 — RefSeq curated summary.

At a glance

• GWAS associations: 26
• Clinical variants (ClinVar): 8 total
• Phenotypes (HPO): 1
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001017915

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6079
Approved symbol	INPP5D
Name	inositol polyphosphate-5-phosphatase D
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Aliases	SHIP, hp51CN, SHIP1
Ensembl gene	ENSG00000168918
Ensembl biotype	protein_coding
OMIM	601582
Entrez	3635

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 6 retained_intron, 4 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000359570, ENST00000415617, ENST00000417661, ENST00000445964, ENST00000451407, ENST00000465281, ENST00000467393, ENST00000472517, ENST00000474278, ENST00000480983, ENST00000491070, ENST00000493078, ENST00000493632, ENST00000496402

RefSeq mRNA: 2 — MANE Select: NM_001017915 NM_001017915, NM_005541

CCDS: CCDS74672, CCDS77543

Canonical transcript exons

ENST00000445964 — 27 exons

Exon	Start	End
ENSE00001123934	233204126	233204717
ENSE00001133836	233198095	233198376
ENSE00001133855	233195399	233195495
ENSE00001133861	233193812	233193961
ENSE00001133868	233189850	233189937
ENSE00001133876	233185843	233185925
ENSE00001133885	233184408	233184521
ENSE00001133957	233163707	233163903
ENSE00001632389	233146367	233146438
ENSE00001637925	233146162	233146242
ENSE00001744299	233158313	233158419
ENSE00001747113	233206706	233207903
ENSE00001750558	233147471	233147594
ENSE00002501705	233161724	233161826
ENSE00003476095	233079335	233079398
ENSE00003478527	233122107	233122257
ENSE00003488825	233182410	233182499
ENSE00003521021	233177265	233177346
ENSE00003557286	233164307	233164424
ENSE00003559919	233170496	233170604
ENSE00003565392	233130508	233130648
ENSE00003570278	233170026	233170164
ENSE00003602687	233169305	233169401
ENSE00003620428	233171064	233171152
ENSE00003680639	233125745	233125919
ENSE00003747233	233139842	233139929
ENSE00003759805	233060342	233060612

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 98.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.4460 / max 1519.6742, expressed in 1022 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26024	24.4308	692
26025	7.9281	618
202613	1.7349	260
202612	1.0667	286
26026	0.6052	225
26023	0.4280	176
26034	0.1523	83
202610	0.0474	16
202611	0.0369	6
26027	0.0157	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.37	gold quality
blood	UBERON:0000178	98.07	gold quality
spleen	UBERON:0002106	97.38	gold quality
lymph node	UBERON:0000029	96.92	gold quality
leukocyte	CL:0000738	95.96	gold quality
monocyte	CL:0000576	95.78	gold quality
bone marrow	UBERON:0002371	95.59	gold quality
bone marrow cell	CL:0002092	95.43	gold quality
vermiform appendix	UBERON:0001154	95.24	gold quality
tonsil	UBERON:0002372	93.59	gold quality
sural nerve	UBERON:0015488	90.37	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.90	gold quality
right lung	UBERON:0002167	89.04	gold quality
small intestine	UBERON:0002108	88.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.59	gold quality
spinal cord	UBERON:0002240	88.54	gold quality
tibial nerve	UBERON:0001323	88.11	gold quality
saliva-secreting gland	UBERON:0001044	88.09	gold quality
placenta	UBERON:0001987	87.97	gold quality
gall bladder	UBERON:0002110	87.73	gold quality
upper lobe of left lung	UBERON:0008952	87.46	gold quality
minor salivary gland	UBERON:0001830	87.45	gold quality
corpus callosum	UBERON:0002336	86.87	gold quality
omental fat pad	UBERON:0010414	86.84	gold quality
substantia nigra	UBERON:0002038	86.74	gold quality
adipose tissue	UBERON:0001013	86.28	gold quality
lung	UBERON:0002048	86.12	gold quality
hypothalamus	UBERON:0001898	85.97	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.97	gold quality
apex of heart	UBERON:0002098	84.47	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	36.55
E-HCAD-35	yes	31.73
E-ANND-3	yes	21.38
E-HCAD-25	yes	14.99
E-CURD-119	yes	6.73
E-MTAB-7606	no	1305.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FLI1, IKZF1, IKZF2, IRF4, NR0B2

miRNA regulators (miRDB)

32 targeting INPP5D, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-7106-3P	97.33	65.33	644
HSA-MIR-335-5P	97.10	68.12	1022
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-3184-3P	96.96	66.91	845
HSA-MIR-4793-5P	96.88	65.90	872
HSA-MIR-597-5P	96.82	67.57	732
HSA-MIR-617	96.79	65.96	738
HSA-MIR-7108-5P	96.42	66.17	598
HSA-MIR-6815-5P	96.05	65.55	662

Literature-anchored findings (GeneRIF, showing 40)

• implicated as regulator of histamine release in basophils (PMID:11692111)
• SHIP localization to membrane receptors and subsequent activation along with the observed inability of SHIP -/- neutrophils to exhibit enhanced apoptosis with the stimulus combination. (PMID:11724799)
• Association of SHIP with releasability in human basophils. (PMID:12217402)
• data demonstrate that CD16 engagement on NK cells induces membrane targeting and activation of SHIP-1, which acts as negative regulator of antibody-dependent cellular cytotoxicity function (PMID:12393695)
• SHIP-1 contributes to degradation of phosphatidylinositol trisphosphate (PI(3,4,5)P3) in T cells and thus influences signaling away from PI(3,4,5)P3-dependent effectors toward effectors that are exclusively driven by phosphatidylinositol 3,4-bisphosphate. (PMID:12421919)
• SHIP expression appears to be differently altered in the early and late stages of differentiation of BCR-ABL-transformed cells (PMID:12829595)
• SHIP-1 and Lyn have roles in the negative regulation of M-CSF-R-induced Akt activation (PMID:12882960)
• SHIP positively, rather than negatively, regulates in vitro membrane recruitment of pleckstrin homology domain-containing signaling proteins Bam32 and TAPP2, which therefore specify a distinct wave of phosphatidylinositol 3-kinase signaling in B cells. (PMID:14688341)
• SHIP1 and Lyn have roles as negative regulators of integrin alpha(IIb)beta(3) adhesive and signaling function (PMID:15166241)
• SHIP1 and SHIP2 interact preferentially with Tec and inactivate it by de-phosphorylation of local PtdIns 3,4,5-P(3) and inhibition of Tec membrane localization (PMID:15492005)
• SHIP1 negatively regulates monokine-induced NK cell IFN-gamma production in vitro and in vivo and provide the first molecular explanation for an important functional distinction observed between CD56bright and CD56dim human NK subsets. (PMID:15604218)
• SHIP has a negative regulatory role in TLR2-induced neutrophil activation and in the development of related in vivo neutrophil-dependent inflammatory processes, such as acute lung injury in transgenic mice. (PMID:15944314)
• Heterologous activation of SHIP by non-G-protein-coupled receptor-mediated routes can impinge on PI3K-dependent signaling pathways activated by independently ligated G-protein-coupled chemokine receptors. (PMID:16038794)
• SHIP1 is necessary for FcgammaRIIB to negatively regulate B cell activation. (PMID:16406061)
• Upregulated in oral mucosa during chronic periodontitis compared to its level during gingival health. (PMID:16428799)
• Study showed H2O2-induced IKK activation in leukemic cells is mediated by SHIP-1; Jurkat cells expressing SHIP-1 are more resistant to H2O2-induced apoptosis than parental cells, suggesting SHIP-1 has an important role in leukemic cell responses to ROS (PMID:16619039)
• Our results indicate that SHIP1 is involved, in a Src kinase-dependent manner, in the early signaling events observed upon the cross-linking of CD32a in human neutrophils. (PMID:16682172)
• SHIP phosphorylation in stimulated human basophils undergoes modest nonspecific desensitization that persists despite dissociation of the desensitizing antigen, resulting in an immunologic memory of prior stimulation. (PMID:16818760)
• SHIP1 not only acts as a negative player in T-cell lines proliferation, but also regulates critical pathways, such as NF-kappaB (nuclear factor kappaB) activation. (PMID:17371259)
• Gene structure, expression profiling and mutation analysis of the tumour suppressor SHIP1 in Caucasian acute myeloid leukaemia (PMID:17657219)
• inactivation of SHIP1 could play a central role in the deregulation of Akt pathway and tumorigenesis, perhaps in conjunction with PTEN inactivation (PMID:19473701)
• Reducing expression of miR-21 or miR-155 led to up-regulation of phosphatase and tensin homologue (PTEN), programmed cell death 4 (PDCD4), or Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1). (PMID:19641183)
• The novel platelet adapter Dok-3 and the structurally related Dok-1 are tyrosine phosphorylated in an Src kinase-independent manner downstream of alphaIIbbeta3 in human platelets, leading to an interaction with SHIP-1. (PMID:19682241)
• Data suggest that a combination of tissue distribution, specificity, and kinetic differences is likely responsible for SHIP1 and SHIP2 in vivo functional differences. (PMID:19839650)
• In B cell lymphoma, elevated levels of miR-155, and consequent diminished SHIP1 expression are the result of autocrine stimulation by TNFalpha. (PMID:19890474)
• wtSHIP gene can down-regulate Akt phosphorylation and up-regulate cell cycle related proteins in K562 cells. (PMID:19954644)
• miR-155 led to down-regulation of SHIP, showing that it specifically targets the SHIP 3’untraslated regions. (PMID:20041145)
• This review summarizes how SHIP participates in normal immune physiology or the pathologies that result when SHIP is mutated. SHIP can have either inhibitory or activating roles in cell signaling. (PMID:21155837)
• Data suggest that SHIP-1 might regulate changes in the cytoskeleton. (PMID:21402888)
• Actin polymerization, F-actin accumulation, and Wiskott-Aldrich symptom protein phosphorylation are enhanced in SHIP-1-deficient B cells in a Bruton’s tyrosine kinase (Btk)-dependent manner. (PMID:21622861)
• indentification of LyGDI as a binding partner of SHIP, associating inducibly with the SHIP/Grb2/Shc complex (PMID:21695085)
• The identification of SHIP1 as a nuclear inositol 5 phosphatase adds another member of the phosphoinositide and inositol modulating molecules to the emerging network of inositide signaling in the nucleus. (PMID:21864674)
• data suggest that miR-155 and miR-210/SHIP-1/Akt pathways could serve as clinical biomarkers for disease progression, and that miR-155 and miR-210 might serve as novel therapeutic targets in myelodysplastic syndromes. (PMID:22249254)
• Mutation in the PxxP domain of SHIP affects cell migration and invasion ability of K562 cells through increased MMP-9 expression, FAK phosphorylation and NF-kappaB activation. (PMID:22575191)
• The CD2AP/SHIP1 complex and Cbl are recruited to blood dendritic cell (DC) antigen 2 (BDCA2) and Fc fragment of IgE high affinity I receptor (FcepsilonR1)gamma complex after BDCA2 cross-linking in human primary plasmacytoid DCs. (PMID:22706086)
• inositol phosphatase SHIP-1 inhibits NOD2-induced NF-kappaB activation by disturbing the interaction of XIAP with RIP2 (PMID:22815893)
• SHIP1 mutant P1039S which does not reduce PI3K/AKT signaling anymore is located in a PXXP SH3 domain consensus binding motif. (PMID:22820502)
• SHIP1 silencing opposes TIGIT/PVR-mediated inhibitory signaling and restores cytotoxicity of YTS cells. (PMID:23154388)
• Tks5 is needed for breast carcinoma cell invadopodium precursor stabilization, where the phox homology (PX) domain of Tks5 interacts with PI(3,4)P2. SHIP2 arrival at the invadopodium precursor coincides with the onset of PI(3,4)P2 accumulation. (PMID:24206842)
• The discovery and replication studies presented here show SHIP-1 to be a risk marker for acute ischemic stroke in the Chinese population, which appears to be a novel finding. (PMID:24352714)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	inpp5d	ENSDARG00000074283
mus_musculus	Inpp5d	ENSMUSG00000026288
rattus_norvegicus	Inpp5d	ENSRNOG00000017020
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), INPP5K (ENSG00000132376), INPP5E (ENSG00000148384), SYNJ1 (ENSG00000159082), INPPL1 (ENSG00000165458), SH2D1A (ENSG00000183918), INPP5J (ENSG00000185133), SH2D1B (ENSG00000198574), INPP5F (ENSG00000198825), INPP5B (ENSG00000204084), SACM1L (ENSG00000211456)

Protein

Protein identifiers

Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 — Q92835 (reviewed: Q92835)

Alternative names: Inositol polyphosphate-5-phosphatase D, Inositol polyphosphate-5-phosphatase of 145 kDa, Phosphatidylinositol 4,5-bisphosphate 5-phosphatase, SH2 domain-containing inositol 5’-phosphatase 1, p150Ship

All UniProt accessions (4): Q92835, H0Y5Q9, H7C403, R4GMN8

UniProt curated annotations — full annotation on UniProt →

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. Able also to hydrolyzes the 5-phosphate of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P3) and inositol 1,3,4,5-tetrakisphosphate. 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.

Subunit / interactions. Interacts with tyrosine phosphorylated form of SHC1. Interacts with tyrosine phosphorylated form of DOK1. Interacts with tyrosine phosphorylated form of DOK3. Interacts with tyrosine phosphorylated form of SLAMF1/CD150. Interacts with PTPN11 in response to IL-3. Interacts with receptor EPOR. Interacts with receptors MS4A2/FCER1B and FCER1G. Interacts with receptors FCGR2B and FCGR3. Interacts with receptor FCGR2A, leading to regulate gene expression during the phagocytic process. Interacts with GRB2. Interacts with PLCG1. Interacts with tyrosine kinases SRC and TEC. Interacts with c-Met/MET. Interacts with MILR1 (tyrosine-phosphorylated). Can weakly interact (via NPXY motif 2) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Interacts with FCRL3 and FCRL6 (tyrosine phosphorylated form). Interacts (via SH2 domain) with tyrosine phosphorylated KLRC1 (via ITIM). Interacts with MPL/TPOR.

Subcellular location. Cytoplasm. Cell membrane. Membrane raft. Cytoskeleton. Membrane.

Tissue specificity. Specifically expressed in immune and hematopoietic cells. Expressed in bone marrow and blood cells. Levels vary considerably within this compartment. Present in at least 74% of immature CD34+ cells, whereas within the more mature population of CD33+ cells, it is present in only 10% of cells. Present in the majority of T-cells, while it is present in a minority of B-cells (at protein level).

Post-translational modifications. Tyrosine phosphorylated by the members of the SRC family after exposure to a diverse array of extracellular stimuli such as cytokines, growth factors, antibodies, chemokines, integrin ligands and hypertonic and oxidative stress. Phosphorylated upon IgG receptor FCGR2B-binding.

Activity regulation. Activated upon translocation to the sites of synthesis of PtdIns(3,4,5)P3 in the membrane.

Domain organisation. The SH2 domain interacts with tyrosine phosphorylated forms of proteins such as SHC1 or PTPN11/SHP-2. It competes with that of GRB2 for binding to phosphorylated SHC1 to inhibit the Ras pathway. It is also required for tyrosine phosphorylation. The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q92835-1	1	yes
Q92835-2	2
Q92835-3	3, SIP-110

RefSeq proteins (2): NP_001017915, NP_005532 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000300	IPPc	Domain
IPR000980	SH2	Domain
IPR036691	Endo/exonu/phosph_ase_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR057509	C2_SHIP1-2_2nd	Domain
IPR057510	C2_SHIP1-2_first	Domain

Pfam: PF00017, PF22669, PF24147, PF24150

Enzyme classification (BRENDA):

• EC 3.1.3.86 — phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase (BRENDA: 6 organisms, 16 substrates, 55 inhibitors, 12 Km, 11 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
1-PHOSPHATIDYL-1D-MYO-INOSITOL 3,4,5-TRISPHOSPHA	0.001–0.088	5
1-PHOSPHATIDYL-1D-MYO-INOSITOL 4,5-BISPHOSPHATE	0.0316–0.1	3
INOSITOL 1,3,4,5-TETRAKISPHOSPHATE	0.082–0.126	3
1D-MYO-INOSITOL 1,3,4,5-TETRAKISPHOSPHATE	0.125	1

Catalyzed reactions (Rhea), 3 shown:

• 1D-myo-inositol 1,3,4,5-tetrakisphosphate + H2O = 1D-myo-inositol 1,3,4-trisphosphate + phosphate (RHEA:11392)
• 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)

UniProt features (84 total): strand 33, helix 15, modified residue 8, compositionally biased region 6, short sequence motif 5, region of interest 4, turn 4, splice variant 3, sequence variant 2, sequence conflict 2, chain 1, domain 1

Structure

Experimental structures (PDB)

99 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6XY7	X-RAY DIFFRACTION	1.09
5RWW	X-RAY DIFFRACTION	1.16
5RW2	X-RAY DIFFRACTION	1.22
5RW7	X-RAY DIFFRACTION	1.23
5RXA	X-RAY DIFFRACTION	1.24
5RWB	X-RAY DIFFRACTION	1.25
5RWV	X-RAY DIFFRACTION	1.25
5RXE	X-RAY DIFFRACTION	1.25
5RWJ	X-RAY DIFFRACTION	1.26
5RXF	X-RAY DIFFRACTION	1.26
5RW8	X-RAY DIFFRACTION	1.27
5RX2	X-RAY DIFFRACTION	1.27
5RWS	X-RAY DIFFRACTION	1.28
5RX5	X-RAY DIFFRACTION	1.28
5RWA	X-RAY DIFFRACTION	1.29
5RWD	X-RAY DIFFRACTION	1.29
5RWI	X-RAY DIFFRACTION	1.29
5RWO	X-RAY DIFFRACTION	1.29
5RX9	X-RAY DIFFRACTION	1.29
8PDI	X-RAY DIFFRACTION	1.3
5RW4	X-RAY DIFFRACTION	1.31
5RX1	X-RAY DIFFRACTION	1.31
5RW6	X-RAY DIFFRACTION	1.32
5RWK	X-RAY DIFFRACTION	1.32
5RWQ	X-RAY DIFFRACTION	1.32
5RYA	X-RAY DIFFRACTION	1.32
5RXD	X-RAY DIFFRACTION	1.33
5RWE	X-RAY DIFFRACTION	1.34
5RWX	X-RAY DIFFRACTION	1.34
5RX8	X-RAY DIFFRACTION	1.34

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92835-F1	72.23	0.44

Functional residue map

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

Post-translational modifications (8): 243, 915, 934, 944, 960, 963, 971, 1022

Function

Pathways and Gene Ontology

Reactome pathways

20 pathways

ID	Pathway
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-1855204	Synthesis of IP3 and IP4 in the cytosol
R-HSA-202424	Downstream TCR signaling
R-HSA-210990	PECAM1 interactions
R-HSA-912526	Interleukin receptor SHC signaling
R-HSA-9680350	Signaling by CSF1 (M-CSF) in myeloid cells
R-HSA-109582	Hemostasis
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1280218	Adaptive Immune System
R-HSA-1430728	Metabolism
R-HSA-1483249	Inositol phosphate metabolism
R-HSA-1483255	PI Metabolism
R-HSA-1483257	Phospholipid metabolism
R-HSA-168256	Immune System
R-HSA-202403	TCR signaling
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-449147	Signaling by Interleukins
R-HSA-451927	Interleukin-2 family signaling
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 397 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_LIPID_MODIFICATION, REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, TAATAAT_MIR126, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_ERYTHROCYTE_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_MYELOID_CELL_HOMEOSTASIS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM

GO Biological Process (29): phosphatidylinositol biosynthetic process (GO:0006661), phosphate-containing compound metabolic process (GO:0006796), apoptotic process (GO:0006915), signal transduction (GO:0007165), determination of adult lifespan (GO:0008340), negative regulation of signal transduction (GO:0009968), immunoglobulin mediated immune response (GO:0016064), negative regulation of B cell proliferation (GO:0030889), negative regulation of interleukin-6 production (GO:0032715), intracellular signal transduction (GO:0035556), positive regulation of apoptotic process (GO:0043065), positive regulation of B cell differentiation (GO:0045579), positive regulation of erythrocyte differentiation (GO:0045648), negative regulation of monocyte differentiation (GO:0045656), negative regulation of neutrophil differentiation (GO:0045659), negative regulation of osteoclast differentiation (GO:0045671), negative regulation of bone resorption (GO:0045779), negative regulation of natural killer cell mediated cytotoxicity (GO:0045953), phosphatidylinositol dephosphorylation (GO:0046856), regulation of immune response (GO:0050776), T cell receptor signaling pathway (GO:0050852), immune system process (GO:0002376), lipid metabolic process (GO:0006629), organophosphate metabolic process (GO:0019637), negative regulation of granulocyte differentiation (GO:0030853), natural killer cell mediated cytotoxicity (GO:0042267), positive regulation of lymphocyte differentiation (GO:0045621), negative regulation of immune response (GO:0050777), negative regulation of B cell activation (GO:0050869)

GO Molecular Function (9): phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity (GO:0004439), inositol-polyphosphate 5-phosphatase activity (GO:0004445), phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity (GO:0016314), SH3 domain binding (GO:0017124), phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity (GO:0034485), inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity (GO:0052659), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), membrane raft (GO:0045121), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Cytokine Signaling in Immune system	2
Immune System	2
Metabolism	2
Signaling by Interleukins	2
PI Metabolism	1
Inositol phosphate metabolism	1
TCR signaling	1
Cell surface interactions at the vascular wall	1
Interleukin-2 family signaling	1
Interleukin-3, Interleukin-5 and GM-CSF signaling	1
Phospholipid metabolism	1
Metabolism of lipids	1
Adaptive Immune System	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
phosphatidylinositol metabolic process	2
signal transduction	2
intracellular anatomical structure	2
negative regulation of myeloid leukocyte differentiation	2
phosphatidylinositol phosphate 5-phosphatase activity	2
phosphatidylinositol trisphosphate phosphatase activity	2
biosynthetic process	1
metabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
multicellular organismal process	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
B cell mediated immunity	1
regulation of B cell proliferation	1
B cell proliferation	1
negative regulation of lymphocyte proliferation	1
negative regulation of B cell activation	1
negative regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
B cell differentiation	1
regulation of B cell differentiation	1
positive regulation of lymphocyte differentiation	1
positive regulation of B cell activation	1
erythrocyte differentiation	1
positive regulation of myeloid cell differentiation	1
regulation of erythrocyte differentiation	1

Protein interactions and networks

STRING

1956 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INPP5D	FCGR2B	P31994	890
INPP5D	GRB2	P29354	882
INPP5D	SHC1	P29353	880
INPP5D	TIGIT	Q495A1	880
INPP5D	TYROBP	O43914	875
INPP5D	CD2AP	Q9Y5K6	849
INPP5D	CLEC7A	Q9BXN2	807
INPP5D	SRC	P12931	796
INPP5D	PTPN6	P29350	779
INPP5D	TREM2	Q9NZC2	752
INPP5D	DOK3	Q7L591	750
INPP5D	IRAK3	Q9Y616	736
INPP5D	CASS4	Q9NQ75	713
INPP5D	ZCWPW1	Q9H0M4	692
INPP5D	NME8	Q8N427	689

IntAct

75 interactions, top by confidence:

A	B	Type	Score
INPP5D	FCGR2B	psi-mi:“MI:0407”(direct interaction)	0.700
INPP5D	FCGR2B	psi-mi:“MI:0914”(association)	0.700
INPP5D	FCGR2B	psi-mi:“MI:0915”(physical association)	0.700
CD244	SH2D1B	psi-mi:“MI:0914”(association)	0.690
INPP5D	CD244	psi-mi:“MI:0407”(direct interaction)	0.670
INPP5D		psi-mi:“MI:0915”(physical association)	0.560
INPP5D	KHDRBS3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	INPP5D	psi-mi:“MI:0915”(physical association)	0.560
INPP5D	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.560
KRT31	INPP5D	psi-mi:“MI:0915”(physical association)	0.560
KRT40	INPP5D	psi-mi:“MI:0915”(physical association)	0.560
INPP5D	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
	INPP5D	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	INPP5D	psi-mi:“MI:0915”(physical association)	0.560
INPP5D	KRT31	psi-mi:“MI:0915”(physical association)	0.560
INPP5D	KRT40	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	INPP5D	psi-mi:“MI:0915”(physical association)	0.560
KHDRBS3	INPP5D	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (101): KRT31 (Two-hybrid), KHDRBS3 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), INPP5D (Two-hybrid), INPP5D (Affinity Capture-Western), INPP5D (Affinity Capture-Western), INPP5D (Affinity Capture-Western), DOK1 (Affinity Capture-Western), DOK2 (Affinity Capture-Western), SHC1 (Affinity Capture-Western), INPP5D (Affinity Capture-Western)

ESM2 similar proteins: A0A8I3NFE2, A0FI79, B1AVH7, B5DFA1, D2H0G5, D7PF45, O00750, O15357, O70143, P29353, P97573, P98083, Q00IB7, Q0IIE2, Q15678, Q16825, Q17R13, Q2I6J0, Q2I6J1, Q2V2M9, Q5JV73, Q5M824, Q5R7W7, Q5U2X5, Q61120, Q62130, Q62136, Q62728, Q62925, Q69Z98, Q6P4S2, Q6P549, Q80TI1, Q8AY68, Q8BMC3, Q8BYW1, Q8IWQ3, Q8K245, Q92529, Q92835

Diamond homologs: A0A8I3NFE2, A0FI79, A0JNB0, A1Y2K1, A6QLK6, B2RZ59, B5KFD7, D3ZGS3, D7PF45, F1RDG9, G5ECJ6, O14306, O14796, O15357, O35324, O60880, O88890, O88900, P00519, P00520, P00521, P00522, P03949, P06239, P06241, P09851, P0CE43, P10447, P17713, P20936, P29350, P29351, P32019, P34370, P39688, P42684, P42685, P42686, P50904, P53356

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
INPP5D	“up-regulates quantity”	“phosphatidylinositol bisphosphate”	“chemical modification”
INPP5D	“down-regulates quantity”	PIP3	“chemical modification”
miR-155	“down-regulates quantity by repression”	INPP5D	“post transcriptional regulation”
ARRB2	“up-regulates activity”	INPP5D	binding
INPP5D	“down-regulates activity”	TRAF6	binding
GRB2	“up-regulates activity”	INPP5D	binding
INPP5D	“down-regulates activity”	PLCG2	dephosphorylation
INPP5D	“down-regulates activity”	SYK	dephosphorylation
LYN	“up-regulates activity”	INPP5D	phosphorylation
SHC1	up-regulates	INPP5D	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 39 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of signaling by CBL	5	88.7×	2e-07
Signaling by CSF1 (M-CSF) in myeloid cells	6	74.2×	3e-08

GO biological processes:

GO term	Partners	Fold	FDR
cell surface receptor protein tyrosine kinase signaling pathway	6	35.9×	6e-06
regulation of cell shape	5	21.2×	5e-04
adaptive immune response	5	14.5×	1e-03
immune response	6	9.7×	1e-03
cell adhesion	7	9.0×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4588 predictions. Top by Δscore:

Variant	Effect	Δscore
2:233060608:GTGCT:G	donor_gain	1.0000
2:233060609:TGCT:T	donor_gain	1.0000
2:233060610:GCT:G	donor_gain	1.0000
2:233060610:GCTG:G	donor_gain	1.0000
2:233060612:TGTG:T	donor_loss	1.0000
2:233060613:G:C	donor_loss	1.0000
2:233060613:G:GG	donor_gain	1.0000
2:233060614:TGAG:T	donor_loss	1.0000
2:233076212:G:GT	donor_gain	1.0000
2:233076224:G:T	donor_gain	1.0000
2:233079329:TTTCA:T	acceptor_loss	1.0000
2:233079330:TTCA:T	acceptor_loss	1.0000
2:233079331:TCAGG:T	acceptor_loss	1.0000
2:233079332:CAGG:C	acceptor_loss	1.0000
2:233079333:A:AG	acceptor_gain	1.0000
2:233079333:A:C	acceptor_loss	1.0000
2:233079334:G:GG	acceptor_gain	1.0000
2:233122093:T:TA	acceptor_gain	1.0000
2:233122098:T:A	acceptor_gain	1.0000
2:233122105:A:AG	acceptor_gain	1.0000
2:233122105:AG:A	acceptor_gain	1.0000
2:233122106:G:GA	acceptor_gain	1.0000
2:233122106:GG:G	acceptor_gain	1.0000
2:233122106:GGCA:G	acceptor_gain	1.0000
2:233122106:GGCAT:G	acceptor_gain	1.0000
2:233122221:G:GT	donor_gain	1.0000
2:233122248:G:GT	donor_gain	1.0000
2:233122254:ACAG:A	donor_loss	1.0000
2:233122255:CAG:C	donor_loss	1.0000
2:233122256:AGG:A	donor_loss	1.0000

AlphaMissense

7828 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:233060521:G:C	A15P	1.000
2:233060531:T:C	L18P	1.000
2:233060534:T:A	L19H	1.000
2:233060534:T:C	L19P	1.000
2:233060554:G:T	G26W	1.000
2:233060555:G:A	G26E	1.000
2:233060555:G:T	G26V	1.000
2:233060560:T:C	F28L	1.000
2:233060561:T:C	F28S	1.000
2:233060562:C:A	F28L	1.000
2:233060562:C:G	F28L	1.000
2:233060564:T:A	L29H	1.000
2:233060564:T:C	L29P	1.000
2:233060569:C:A	R31S	1.000
2:233060570:G:C	R31P	1.000
2:233060603:T:A	L42H	1.000
2:233060603:T:C	L42P	1.000
2:233079349:T:A	V50D	1.000
2:233079357:T:G	Y53D	1.000
2:233079362:A:C	R54S	1.000
2:233079362:A:T	R54S	1.000
2:233079394:T:A	V65D	1.000
2:233122153:T:C	L82P	1.000
2:233122186:T:C	L93P	1.000
2:233158322:T:C	L347P	1.000
2:233158329:G:C	K349N	1.000
2:233158329:G:T	K349N	1.000
2:233158406:T:C	F375S	1.000
2:233161746:T:C	L387P	1.000
2:233161817:T:A	W411R	1.000

dbSNP variants (sampled 300 via entrez): RS1000019992 (2:233059039 C>T), RS1000047269 (2:233083412 C>A), RS1000049097 (2:233191018 C>G), RS1000066593 (2:233131753 G>A), RS1000073806 (2:233096062 G>A), RS1000079737 (2:233080596 G>A,T), RS1000099025 (2:233176942 A>G), RS1000099325 (2:233199033 T>C), RS1000119673 (2:233088685 G>A), RS1000156710 (2:233154591 C>G,T), RS1000190851 (2:233199194 C>T), RS1000200114 (2:233129806 C>G), RS1000203869 (2:233073634 C>A,G), RS1000237081 (2:233114130 G>A,C), RS1000298359 (2:233121061 G>C)

Disease associations

OMIM: gene MIM:601582 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): severe combined immunodeficiency (MONDO:0015974)

Orphanet (1): Severe combined immunodeficiency (Orphanet:183660)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0004430	Severe combined immunodeficiency

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST001438_2	Crohn’s disease	1.000000e-12
GCST001729_11	Crohn’s disease	4.000000e-70
GCST002238_4	Contrast sensitivity	4.000000e-06
GCST002245_13	Alzheimer’s disease (late onset)	3.000000e-08
GCST003830_47	Response to bronchodilator in chronic obstructive pulmonary disease (change in FEV1)	1.000000e-06
GCST004600_179	Eosinophil percentage of white cells	3.000000e-20
GCST004606_53	Eosinophil count	2.000000e-14
GCST004617_74	Eosinophil percentage of granulocytes	6.000000e-20
GCST004623_168	Neutrophil percentage of granulocytes	2.000000e-19
GCST004624_60	Sum eosinophil basophil counts	2.000000e-13
GCST004864_24	Perceived unattractiveness to mosquitoes	3.000000e-06
GCST005038_25	Allergic disease (asthma, hay fever or eczema)	1.000000e-10
GCST007319_19	Alzheimer’s disease (late onset)	8.000000e-06
GCST007320_105	Alzheimer’s disease or family history of Alzheimer’s disease	5.000000e-09
GCST007321_7	Family history of Alzheimer’s disease	6.000000e-06
GCST90002381_334	Eosinophil count	1.000000e-10
GCST90002381_335	Eosinophil count	2.000000e-24
GCST90002382_88	Eosinophil percentage of white cells	7.000000e-11
GCST90002382_89	Eosinophil percentage of white cells	5.000000e-34
GCST90002385_466	High light scatter reticulocyte count	9.000000e-11
GCST90002386_536	High light scatter reticulocyte percentage of red cells	2.000000e-11
GCST90002387_63	Immature fraction of reticulocytes	1.000000e-12
GCST90002387_64	Immature fraction of reticulocytes	6.000000e-13
GCST90002393_394	Monocyte count	4.000000e-09
GCST90002398_118	Neutrophil count	9.000000e-10
GCST90011900_176	Serum alkaline phosphatase levels	3.000000e-10

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0005419	contrast sensitivity measurement
EFO:0005921	FEV change measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0008380	perceived unattractiveness to mosquitos measurement
EFO:0009268	family history of Alzheimer’s disease
EFO:0007986	reticulocyte count
EFO:0005091	monocyte count
EFO:0004833	neutrophil count
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016511	Severe Combined Immunodeficiency	C16.320.798.750; C16.614.815; C18.452.284.800; C20.673.795.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1781870 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Inositol polyphosphate phosphatases

ChEMBL bioactivities

6 potent at pChembl≥5 of 26 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.60	IC50	2500	nM	CHEMBL5271592
5.58	Kd	2652	nM	MOLIBRESIB
5.50	Ki	3200	nM	CHEMBL6120493
5.37	IC50	4320	nM	MOLIBRESIB
5.22	IC50	6000	nM	CHEMBL6144748
5.21	IC50	6100	nM	CHEMBL6120493

PubChem BioAssay actives

3 with measured affinity, of 26 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3R,5S,8R,9R,10S,13R,14R,17R)-8,10,13-trimethyl-17-[(2R)-6-methylheptan-2-yl]-1,2,3,4,5,6,7,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-amine;hydrochloride	1938005: Inhibition of SHIP1 (unknown origin)	ic50	2.5000	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179198: Binding affinity against INPP5D (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	2.6520	uM

CTD chemical–gene interactions

62 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, increases methylation	7
methylmercuric chloride	increases expression, affects cotreatment	4
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	4
sodium arsenite	decreases expression, increases expression	3
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Cisplatin	affects expression, increases expression	2
Nickel	increases expression	2
Ozone	affects expression, increases abundance, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tretinoin	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	increases expression	1
sotorasib	decreases expression, affects cotreatment	1
dicrotophos	increases expression	1
lasiocarpine	increases expression	1
triphenyl phosphate	affects expression	1
quercitrin	affects expression	1
trichostatin A	increases expression	1
pyrazolo(3,4-d)pyrimidine	affects expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation, decreases methylation	1
aflatoxin B2	increases methylation	1
cupric chloride	decreases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
tricetin	increases expression	1

ChEMBL screening assays

16 unique, capped per target: 16 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1785363	Binding	Activation of SHIP1 using IP4 as substrate at 10 uM preincubated for 10 mins before addition of IP4 measured after 10 mins	Turnagainolides A and B, cyclic depsipeptides produced in culture by a Bacillus sp.: isolation, structure elucidation, and synthesis. — J Nat Prod

Cellosaurus cell lines

423 cell lines: 423 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0065	Jurkat	Cancer cell line	Male
CVCL_0354	J.CaM1.6	Cancer cell line	Male
CVCL_0367	Jurkat E6.1	Cancer cell line	Male
CVCL_0584	Jurkat Wurzburg	Cancer cell line	Male
CVCL_0D86	JPX-9	Cancer cell line	Male
CVCL_1061	Jurkat clone A3	Cancer cell line	Male
CVCL_1316	J.RT3-T3.5	Cancer cell line	Male
CVCL_1E01	JLTRG	Cancer cell line	Male
CVCL_1E02	JLTRG-R5	Cancer cell line	Male
CVCL_1F94	Jurkat-HXBc2(4)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT01420627	PHASE3	COMPLETED	EZN-2279 in Patients With ADA-SCID
NCT06940570	PHASE3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT00000603	PHASE2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00794508	PHASE2	COMPLETED	MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID
NCT01182675	PHASE2	TERMINATED	Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02177760	PHASE2	WITHDRAWN	Sirolimus Prophylaxis for aGVHD in TME SCID
NCT03619551	PHASE2	ACTIVE_NOT_RECRUITING	Conditioning SCID Infants Diagnosed Early
NCT00008450	PHASE1	COMPLETED	Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant
NCT00028236	PHASE1	COMPLETED	Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID)
NCT00152100	PHASE1	COMPLETED	Transplantation of Hematopoietic Cells in Children With Severe Combined Immunodeficiency Syndrome
NCT02860559	PHASE1	UNKNOWN	Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency
NCT01019876	PHASE2/PHASE3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT00228852	PHASE1/PHASE2	COMPLETED	IMM 0212: Busulfan With Fludarabine and Antithymocyte Globulin as Preparative Therapy for Hematopoietic Stem Cell Transplant for the Treatment of Severe Congenital T-Cell Immunodeficiency
NCT00579137	PHASE1/PHASE2	TERMINATED	Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders
NCT01129544	PHASE1/PHASE2	COMPLETED	Gene Transfer for Severe Combined Immunodeficiency, X-linked (SCID-X1) Using a Self-inactivating (SIN) Gammaretroviral Vector
NCT01852370	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT02127892	PHASE1/PHASE2	TERMINATED	SCID Bu/Flu/ATG Study With T Cell Depletion
NCT02963064	PHASE1/PHASE2	TERMINATED	JSP191 Antibody Targeting Conditioning in SCID Patients
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT03538899	PHASE1/PHASE2	RECRUITING	Autologous Gene Therapy for Artemis-Deficient SCID
NCT03597594	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Haplocompatible Transplant Using TCRα/β Depletion Followed by CD45RA-Depleted Donor Lymphocyte Infusions for Severe Combined Immunodeficiency (SCID)
NCT00001255	Not specified	COMPLETED	Gene Transfer Therapy for Severe Combined Immunodeficieny Disease (SCID) Due to Adenosine Deaminase (ADA) Deficiency: A Natural History Study
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT00006335	Not specified	COMPLETED	Influences on Female Adolescents’ Decisions Regarding Testing for Carrier Status of XSCID
NCT00055172	Not specified	RECRUITING	Genetic Basis of Immunodeficiency
NCT00695279	Not specified	COMPLETED	Long Term Follow Up Of Patients Who Have Received Gene Therapy Or Gene Marked Products
NCT00845416	Not specified	COMPLETED	Newborn Screening for Severe Combined Immunodeficiency (SCID) in a High-Risk Population
NCT01186913	Not specified	ENROLLING_BY_INVITATION	Natural History Study of SCID Disorders
NCT01346150	Not specified	UNKNOWN	Patients Treated for SCID (1968-Present)
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
NCT01953016	Not specified	COMPLETED	Participation in a Research Registry for Immune Disorders
NCT02231983	Not specified	UNKNOWN	Clinical Characteristics and Genetic Profiles of Severe Combined Immunodeficiency in China
NCT02590328	Not specified	COMPLETED	Neonatal Screening of Severe Combined Immunodeficiencies
NCT04049084	Not specified	ENROLLING_BY_INVITATION	An Observational LTFU Study for Patients Previously Treated With Autologous ex Vivo Gene Therapy for ADA-SCID
NCT04172181	Not specified	UNKNOWN	Multi-center Clinical Study of Cord Blood Stem Cell Transplantation for SCID
NCT04246840	Not specified	COMPLETED	Study Through Imaging of Visceral Lymphoid Organs in Patients With SCID Who Have Recieved Bone Marrow Allograft
NCT04331483	Not specified	WITHDRAWN	A Study to Assess a Physical Activity Program in Children, Adolescents and Young Adults Requiring Hematopoietic Stem Cell Allografts