PPIP5K1

Summary

PPIP5K1 (diphosphoinositol pentakisphosphate kinase 1, HGNC:29023) is a protein-coding gene on chromosome 15q15.3, encoding Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1 (Q6PFW1). Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4.

This gene encodes a dual functional inositol kinase. The encoded enzyme converts inositol hexakisphosphate to diphosphoinositol pentakisphosphate and diphosphoinositol pentakisphosphate to bis-diphosphoinositol tetrakisphosphate. This protein may be important for intracellular signaling pathways. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 15.

Source: NCBI Gene 9677 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 70 total
• Druggable target: yes
• MANE Select transcript: NM_001394395

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29023
Approved symbol	PPIP5K1
Name	diphosphoinositol pentakisphosphate kinase 1
Location	15q15.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0377, IPS1, VIP1
Ensembl gene	ENSG00000168781
Ensembl biotype	protein_coding
OMIM	610979
Entrez	9677

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 29 protein_coding, 6 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000334933, ENST00000360135, ENST00000360301, ENST00000381879, ENST00000381885, ENST00000396923, ENST00000417085, ENST00000420765, ENST00000427877, ENST00000429176, ENST00000431962, ENST00000432870, ENST00000437065, ENST00000439195, ENST00000453080, ENST00000462136, ENST00000465123, ENST00000469229, ENST00000472547, ENST00000476294, ENST00000488490, ENST00000488768, ENST00000644537, ENST00000707073, ENST00000851781, ENST00000851782, ENST00000851783, ENST00000927131, ENST00000927132, ENST00000927133, ENST00000927134, ENST00000927135, ENST00000927136, ENST00000965891, ENST00000965892, ENST00000965893, ENST00000965894, ENST00000965895

RefSeq mRNA: 29 — MANE Select: NM_001394395 NM_001130858, NM_001130859, NM_001190214, NM_001354382, NM_001354383, NM_001354384, NM_001354385, NM_001354386, NM_001354387, NM_001354388, NM_001354389, NM_001354390, NM_001354391, NM_001354392, NM_001354393, NM_001354394, NM_001354395, NM_001354396, NM_001354397, NM_001354398, NM_001354399, NM_001354400, NM_001354401, NM_001354402, NM_001393969, NM_001393970, NM_001393971, NM_001394395, NM_014659

CCDS: CCDS32215, CCDS45252, CCDS53937, CCDS86452, CCDS91989

Canonical transcript exons

ENST00000420765 — 32 exons

Exon	Start	End
ENSE00001146319	43539470	43539583
ENSE00001555902	43533475	43535476
ENSE00001614067	43584799	43584892
ENSE00001621572	43560413	43560595
ENSE00001646451	43590172	43590208
ENSE00001753134	43568463	43568553
ENSE00001774689	43564103	43564165
ENSE00003477857	43572769	43572876
ENSE00003504309	43573357	43573484
ENSE00003506843	43581853	43581954
ENSE00003561443	43573034	43573148
ENSE00003563669	43577876	43577951
ENSE00003566993	43577453	43577535
ENSE00003576241	43578070	43578156
ENSE00003576695	43581227	43581388
ENSE00003586891	43571412	43571576
ENSE00003616265	43582095	43582249
ENSE00003624786	43579019	43579120
ENSE00003634379	43577622	43577731
ENSE00003636859	43576827	43576948
ENSE00003655189	43581002	43581123
ENSE00003657261	43576371	43576553
ENSE00003660825	43577108	43577239
ENSE00003672881	43573809	43574032
ENSE00003672892	43582862	43582952
ENSE00003673706	43582564	43582649
ENSE00003681331	43571724	43571840
ENSE00003681545	43574222	43574363
ENSE00003689020	43558795	43558932
ENSE00003691074	43584358	43584532
ENSE00003784789	43583404	43583599
ENSE00003788646	43564867	43564992

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 97.39.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.39	gold quality
cerebellar hemisphere	UBERON:0002245	97.24	gold quality
cerebellar cortex	UBERON:0002129	97.18	gold quality
cerebellum	UBERON:0002037	95.87	gold quality
colonic epithelium	UBERON:0000397	93.51	gold quality
sural nerve	UBERON:0015488	93.17	gold quality
rectum	UBERON:0001052	92.27	gold quality
pituitary gland	UBERON:0000007	91.25	gold quality
adenohypophysis	UBERON:0002196	90.56	gold quality
right lobe of thyroid gland	UBERON:0001119	90.35	gold quality
right frontal lobe	UBERON:0002810	90.33	gold quality
left lobe of thyroid gland	UBERON:0001120	89.35	gold quality
right adrenal gland	UBERON:0001233	89.28	gold quality
islet of Langerhans	UBERON:0000006	89.00	gold quality
right adrenal gland cortex	UBERON:0035827	88.96	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.81	gold quality
prefrontal cortex	UBERON:0000451	88.76	gold quality
small intestine	UBERON:0002108	88.72	gold quality
thyroid gland	UBERON:0002046	88.65	gold quality
left adrenal gland	UBERON:0001234	88.61	gold quality
left adrenal gland cortex	UBERON:0035825	88.28	gold quality
transverse colon	UBERON:0001157	88.24	gold quality
minor salivary gland	UBERON:0001830	88.24	gold quality
adrenal gland	UBERON:0002369	87.67	gold quality
adrenal cortex	UBERON:0001235	87.57	gold quality
right testis	UBERON:0004534	87.57	gold quality
right uterine tube	UBERON:0001302	87.50	gold quality
left testis	UBERON:0004533	87.45	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.41	gold quality
gall bladder	UBERON:0002110	87.28	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-124858	no	31.12
E-ANND-3	no	5.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting PPIP5K1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-5787	99.22	67.86	2628

Literature-anchored findings (GeneRIF, showing 4)

• Upon activation of the appropriate cell-surface receptors to stimulate PtdIns(3,4,5)P3 synthesis, human PPIP5K1 translocates from the cytoplasm to the plasma membrane. (PMID:21222653)
• results suggest that PPIP5K1 might play an important role in regulating function of exocyst complex in establishing cellular polarity and directional migration of cells (PMID:26854614)
• PPIP5K is a rare example of a single protein that catalyzes a kinase/phosphatase futile cycle. (Review) (PMID:27776974)
• This study characterized kinetic properties of the bifunctional inositol pyrophosphate 5-diphosphoinositol 1,2,3,4,6-pentakisphosphatekinase/inositol pyrophosphate, 1,5-bisdiphosphoinositol 2,3,4,6-tetrakisphosphate phosphatase activities of full-length diphosphoinositol pentakisphosphate kinase 1 and 2. (PMID:28126903)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppip5k1b	ENSDARG00000073909
danio_rerio	ppip5k1a	ENSDARG00000076143
mus_musculus	Ppip5k1	ENSMUSG00000033526
rattus_norvegicus	Mfap1a	ENSRNOG00000014436
drosophila_melanogaster	l(1)G0196	FBGN0027279
caenorhabditis_elegans	F46F11.1	WBGENE00018508

Paralogs (1): PPIP5K2 (ENSG00000145725)

Protein

Protein identifiers

Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1 — Q6PFW1 (reviewed: Q6PFW1)

Alternative names: Diphosphoinositol pentakisphosphate kinase 1, Histidine acid phosphatase domain-containing protein 2A, IP6 kinase, Inositol pyrophosphate synthase 1, InsP6 and PP-IP5 kinase 1, VIP1 homolog

All UniProt accessions (12): Q6PFW1, A0A2R8YGT1, A0A8J8ZH50, A0A9L9PYJ9, B7WPL9, C9J490, C9J5E6, C9JZX6, F8W9A8, H0Y3Y5, H7C398, H7C436

UniProt curated annotations — full annotation on UniProt →

Function. Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4. PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation. Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4. Alternatively, phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to produce (PP)2-InsP4. Activated when cells are exposed to hyperosmotic stress.

Subcellular location. Cytoplasm. Cytosol. Cell membrane.

Tissue specificity. Widely expressed, with a higher expression in skeletal muscle, heart and brain.

Domain organisation. The C-terminal acid phosphatase-like domain binds PtdIns(3,4,5)P3 and InsP6. Despite its similarity with the phosphatase domain of histidine acid phosphatases, it has no phosphatase activity.

Similarity. Belongs to the histidine acid phosphatase family. VIP1 subfamily.

Isoforms (7)

UniProt ID	Names	Canonical?
Q6PFW1-1	1	yes
Q6PFW1-2	2
Q6PFW1-3	3
Q6PFW1-4	4
Q6PFW1-5	5
Q6PFW1-6	6
Q6PFW1-7	7

RefSeq proteins (29): NP_001124330, NP_001124331, NP_001177143, NP_001341311, NP_001341312, NP_001341313, NP_001341314, NP_001341315, NP_001341316, NP_001341317, NP_001341318, NP_001341319, NP_001341320, NP_001341321, NP_001341322, NP_001341323, NP_001341324, NP_001341325, NP_001341326, NP_001341327, NP_001341328, NP_001341329, NP_001341330, NP_001341331, NP_001380898, NP_001380899, NP_001380900, NP_001381324, NP_055474 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000560	His_Pase_clade-2	Family
IPR029033	His_PPase_superfam	Homologous_superfamily
IPR033379	Acid_Pase_AS	Active_site
IPR037446	His_Pase_VIP1	Family
IPR040557	VIP1_N	Domain

Pfam: PF00328, PF18086

Enzyme classification (BRENDA):

• EC 2.7.4.21 — inositol-hexakisphosphate 5-kinase (BRENDA: 10 organisms, 35 substrates, 31 inhibitors, 11 Km, 1 kcat entries)
• EC 2.7.4.24 — diphosphoinositol-pentakisphosphate 1-kinase (BRENDA: 5 organisms, 22 substrates, 20 inhibitors, 12 Km, 5 kcat entries)
• EC 3.6.1.B18 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Substrate kinetics (BRENDA)

14 substrates with measured Km, best-characterized 14. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.037–1.4	4
INOSITOL HEXAKISPHOSPHATE	0.0007–0.0061	3
ADP	0.0052–1.39	3
1D-MYO-INOSITOL 5-DIPHOSPHATE PENTAKISPHOSPHATE	0.0001–0.0002	2
ATP	0.022–1.89	2
1D-MYO-INOSITOL HEXAKISPHOSPHATE	0.0004	1
5-DIPHOSPHO-1D-MYO-INOSITOL (1,2,3,4,6)PENTAKISP	0.002	1
ADP	1.57	1
D-MYO-INOSITOL-1,3,4,5,6-PENTAKISPHOSPHATE	0.0055	1
1,5-BIS-DIPHOSPHO-1D-MYO-INOSITOL 2,3,4,6-TETRAK	—	1
1-DIPHOSPHO-1D-MYO-INOSITOL 2,3,4,5,6-PENTAKISPH	0.0001	1
1D-MYO-INOSITOL 1,5-BIS(DIPHOSPHATE) 2,3,4,6-TET	1.94	1
5-DIPHOSPHO-1D-MYO-INOSITOL 1,2,3,4,6-PENTAKISPH	0.0001	1
DIPHOSPHOINOSITOL PENTAKISPHOSPHATE	0.7	1

Catalyzed reactions (Rhea), 2 shown:

• 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate + ATP + H(+) = 1,5-bis(diphospho)-1D-myo-inositol 2,3,4,6-tetrakisphosphate + ADP (RHEA:10276)
• 1D-myo-inositol hexakisphosphate + ATP = 1-diphospho-1D-myo-inositol 2,3,4,5,6-pentakisphosphate + ADP (RHEA:37459)

UniProt features (62 total): sequence conflict 20, binding site 14, splice variant 10, modified residue 6, compositionally biased region 5, region of interest 4, mutagenesis site 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PFW1-F1	65.02	0.30

Functional residue map

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

Ligand- & substrate-binding residues (14): 64–65; 145; 198; 205; 224–225; 224; 248–251; 257–259; 259; 273; 275; 320 …

Post-translational modifications (6): 944, 987, 1037, 1073, 1145, 1152

Mutagenesis-validated functional residues (2):

Position	Phenotype
399	decreases 8-fold the affinity for ptdins(3,4,5)p3.
417	decreases 16-fold the affinity for ptdins(3,4,5)p3.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1855167	Synthesis of pyrophosphates in the cytosol

MSigDB gene sets: 108 (showing top): GOBP_INOSITOL_PHOSPHATE_METABOLIC_PROCESS, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, CADWELL_ATG16L1_TARGETS_DN, GOBP_INOSITOL_METABOLIC_PROCESS, GOBP_ALCOHOL_BIOSYNTHETIC_PROCESS, GOBP_POLYOL_BIOSYNTHETIC_PROCESS, GOBP_ALCOHOL_METABOLIC_PROCESS, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, GOMF_KINASE_ACTIVITY, YKACATTT_UNKNOWN, GOMF_PHOSPHOTRANSFERASE_ACTIVITY_PHOSPHATE_GROUP_AS_ACCEPTOR, GAZDA_DIAMOND_BLACKFAN_ANEMIA_ERYTHROID_DN

GO Biological Process (3): inositol metabolic process (GO:0006020), inositol phosphate biosynthetic process (GO:0032958), inositol phosphate metabolic process (GO:0043647)

GO Molecular Function (10): inositol-1,3,4,5,6-pentakisphosphate kinase activity (GO:0000827), inositol hexakisphosphate kinase activity (GO:0000828), diphosphoinositol pentakisphosphate kinase activity (GO:0000829), inositol hexakisphosphate 5-kinase activity (GO:0000832), ATP binding (GO:0005524), 5-diphosphoinositol pentakisphosphate 1-kinase activity (GO:0033857), inositol hexakisphosphate 1-kinase activity (GO:0052723), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (4): cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Inositol phosphate metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphotransferase activity, phosphate group as acceptor	3
inositol phosphate kinase activity	3
cellular anatomical structure	3
polyol metabolic process	2
inositol hexakisphosphate kinase activity	2
inositol phosphate metabolic process	1
polyol biosynthetic process	1
organophosphate biosynthetic process	1
organophosphate metabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
diphosphoinositol pentakisphosphate kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cytoplasm	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

766 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPIP5K1	IP6K1	Q92551	973
PPIP5K1	IP6K3	Q96PC2	955
PPIP5K1	IP6K2	Q9UHH9	937
PPIP5K1	CATSPER2	Q96P56	927
PPIP5K1	STRC	Q7RTU9	918
PPIP5K1	CKMT1B	P12532	867
PPIP5K1	VIP	P01282	852
PPIP5K1	IPPK	Q9H8X2	804
PPIP5K1	IPMK	Q8NFU5	718
PPIP5K1	ADCYAP1	P18509	700
PPIP5K1	VIPR1	P32241	665
PPIP5K1	SCT	P09683	658
PPIP5K1	DHX58	Q96C10	650
PPIP5K1	ITPK1	Q13572	619
PPIP5K1	A0A2R8Y809	A0A2R8Y809	598
PPIP5K1	TBCE	Q15813	598

IntAct

39 interactions, top by confidence:

A	B	Type	Score
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
CETN1	SFI1	psi-mi:“MI:0914”(association)	0.640
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
MAD2L1	PPIP5K2	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
PPIP5K1	MYH14	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350
DUSP16	MEIOC	psi-mi:“MI:0914”(association)	0.350
ZHX1-C8orf76	FANCG	psi-mi:“MI:0914”(association)	0.350
ATG7	IFT56	psi-mi:“MI:0914”(association)	0.350
FAM167A	IFT56	psi-mi:“MI:0914”(association)	0.350
INF2	PIPSL	psi-mi:“MI:0914”(association)	0.350
PLEKHG7	MROH6	psi-mi:“MI:0914”(association)	0.350
EEF1AKMT3	SMCHD1	psi-mi:“MI:0914”(association)	0.350
HES6	RGPD3	psi-mi:“MI:0914”(association)	0.350
UBXN6	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
C9orf163	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
PUDP	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
CRYBB3	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
UPP1	A2ML1	psi-mi:“MI:0914”(association)	0.350
SF3B3	MYO9A	psi-mi:“MI:0914”(association)	0.350
NSUN5P1		psi-mi:“MI:0914”(association)	0.350
CIAO2A		psi-mi:“MI:0914”(association)	0.350
PPARD	ACACB	psi-mi:“MI:0914”(association)	0.350
NPRL2	APAF1	psi-mi:“MI:0914”(association)	0.350
NFKBIB	APAF1	psi-mi:“MI:0914”(association)	0.350
NT5C	APAF1	psi-mi:“MI:0914”(association)	0.350
CIB2	APAF1	psi-mi:“MI:0914”(association)	0.350
DHDH	ZNF185	psi-mi:“MI:0914”(association)	0.350

BioGRID (55): PPIP5K1 (Affinity Capture-RNA), PPIP5K1 (Affinity Capture-MS), PPIP5K1 (Affinity Capture-RNA), PPIP5K1 (Proximity Label-MS), PPIP5K1 (Affinity Capture-MS), PPIP5K1 (Affinity Capture-MS), PPIP5K1 (Affinity Capture-MS), PPIP5K1 (Affinity Capture-MS), PPIP5K1 (Affinity Capture-MS), PPIP5K1 (Affinity Capture-MS), PPIP5K1 (Affinity Capture-MS), PPIP5K1 (Affinity Capture-MS), PPIP5K1 (Affinity Capture-MS), PPIP5K1 (Affinity Capture-MS), PPIP5K1 (Affinity Capture-MS)

ESM2 similar proteins: A0JMH0, A2ARP1, A5PK74, A7Z050, A9JTG5, B5DE73, B5DFG1, D3YY23, D3ZU57, O00562, O35954, O43304, P0C644, P0CB42, P16386, Q01433, Q02356, Q09200, Q10468, Q32P28, Q3SZL5, Q3U308, Q3V1T4, Q4KLM6, Q5HZW3, Q5RDF1, Q5RF50, Q5U2N3, Q5ZMM1, Q68J42, Q6ICH7, Q6JHU7, Q6PD26, Q6PFW1, Q6YRM6, Q80VP9, Q86TL0, Q8BGV9, Q8BGW1, Q8CG71

Diamond homologs: A2ARP1, A7Z050, F4J8C6, O43314, O74429, P0C644, P91309, Q06685, Q5RDF1, Q5REW0, Q5XHF8, Q6PFW1, Q6ZQB6, Q84WW3, Q9VR59, Q9CMJ8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5115 predictions. Top by Δscore:

Variant	Effect	Δscore
15:43535473:CTGT:C	acceptor_gain	1.0000
15:43535474:TGTC:T	acceptor_loss	1.0000
15:43535477:C:CA	acceptor_loss	1.0000
15:43535477:C:CC	acceptor_gain	1.0000
15:43535478:T:A	acceptor_loss	1.0000
15:43558931:CC:C	acceptor_gain	1.0000
15:43558932:CC:C	acceptor_gain	1.0000
15:43568457:CCATA:C	donor_loss	1.0000
15:43568458:CATA:C	donor_loss	1.0000
15:43568459:ATACC:A	donor_loss	1.0000
15:43568460:TACCT:T	donor_loss	1.0000
15:43568461:ACCT:A	donor_loss	1.0000
15:43568552:ACC:A	acceptor_loss	1.0000
15:43568554:C:CA	acceptor_loss	1.0000
15:43568555:T:A	acceptor_loss	1.0000
15:43569272:T:TA	donor_gain	1.0000
15:43571410:ACCT:A	donor_gain	1.0000
15:43571411:CCTC:C	donor_gain	1.0000
15:43571413:T:TA	donor_gain	1.0000
15:43571572:TCATT:T	acceptor_gain	1.0000
15:43571573:CATT:C	acceptor_gain	1.0000
15:43571573:CATTC:C	acceptor_gain	1.0000
15:43571574:ATT:A	acceptor_gain	1.0000
15:43571575:TT:T	acceptor_gain	1.0000
15:43571576:TC:T	acceptor_loss	1.0000
15:43571577:C:CC	acceptor_gain	1.0000
15:43571577:CT:C	acceptor_loss	1.0000
15:43571579:A:AC	acceptor_gain	1.0000
15:43571579:A:C	acceptor_gain	1.0000
15:43571582:C:CT	acceptor_gain	1.0000

AlphaMissense

9804 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:43573089:C:A	S841I	1.000
15:43573095:A:G	F839S	1.000
15:43573101:A:G	L837P	1.000
15:43573985:A:G	W716R	1.000
15:43573985:A:T	W716R	1.000
15:43576549:A:G	L593P	1.000
15:43576553:C:G	G592R	1.000
15:43576831:G:T	A590D	1.000
15:43576833:G:C	F589L	1.000
15:43576833:G:T	F589L	1.000
15:43576834:A:G	F589S	1.000
15:43576835:A:G	F589L	1.000
15:43576843:G:T	A586D	1.000
15:43576870:G:A	S577F	1.000
15:43576873:G:T	A576D	1.000
15:43576885:A:G	L572P	1.000
15:43577143:C:T	G539E	1.000
15:43577144:C:A	G539W	1.000
15:43577144:C:G	G539R	1.000
15:43577144:C:T	G539R	1.000
15:43577146:A:G	L538P	1.000
15:43577190:C:A	W523C	1.000
15:43577190:C:G	W523C	1.000
15:43577192:A:G	W523R	1.000
15:43577192:A:T	W523R	1.000
15:43577509:C:G	R488P	1.000
15:43577523:G:C	F483L	1.000
15:43577523:G:T	F483L	1.000
15:43577524:A:G	F483S	1.000
15:43577525:A:G	F483L	1.000

dbSNP variants (sampled 300 via entrez): RS1000048187 (15:43533933 C>T), RS1000140531 (15:43563035 A>G), RS1000327933 (15:43540193 A>G), RS1000331662 (15:43558378 C>T), RS1000381673 (15:43539789 G>A), RS1000486287 (15:43540480 C>T), RS1000855411 (15:43554861 G>A), RS1000901994 (15:43554620 TACACACACACACAG>T), RS1000985577 (15:43552355 C>G,T), RS1001029112 (15:43548879 T>C), RS1001051832 (15:43558566 A>G), RS1001087667 (15:43551653 A>G), RS1001314392 (15:43557629 T>C), RS1001327974 (15:43541756 A>T), RS1001366743 (15:43559971 T>A,C)

Disease associations

OMIM: gene MIM:610979 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001808_11	Tumor biomarkers	1.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005127	cancer biomarker measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5046 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
bisphenol F	affects cotreatment, decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
beta-lapachone	decreases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
Acrolein	increases abundance, affects cotreatment, decreases expression, increases oxidation	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Calcitriol	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Ozone	increases abundance, affects cotreatment, decreases expression, increases oxidation	1
Testosterone	decreases expression	1
Vanadates	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Cyclosporine	increases methylation	1
Gold Compounds	increases expression	1
Lactic Acid	increases expression	1
tert-Butylhydroperoxide	decreases expression	1
Volatile Organic Compounds	affects cotreatment, decreases expression, increases oxidation	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3102182	Binding	Inhibition of human VIP1 receptor at 10 uM relative to control	Discovery of 2,5-diarylnicotinamides as selective orexin-2 receptor antagonists (2-SORAs). — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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