ITPRIP

Summary

ITPRIP (inositol 1,4,5-trisphosphate receptor interacting protein, HGNC:29370) is a protein-coding gene on chromosome 10q25.1, encoding Inositol 1,4,5-trisphosphate receptor-interacting protein (Q8IWB1). Enhances Ca(2+)-mediated inhibition of inositol 1,4,5-triphosphate receptor (ITPR) Ca(2+) release.

This gene encodes a membrane-associated protein that binds the inositol 1,4,5-trisphosphate receptor (ITPR). The encoded protein enhances the sensitivity of ITPR to intracellular calcium signaling. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 85450 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 112 total
• MANE Select transcript: NM_001272013

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29370
Approved symbol	ITPRIP
Name	inositol 1,4,5-trisphosphate receptor interacting protein
Location	10q25.1
Locus type	gene with protein product
Status	Approved
Aliases	bA127L20.2, DANGER, D1A
Ensembl gene	ENSG00000148841
Ensembl biotype	protein_coding
OMIM	620205
Entrez	85450

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000278071, ENST00000337478, ENST00000358187, ENST00000458723, ENST00000647721, ENST00000877295, ENST00000877296, ENST00000877297, ENST00000877298, ENST00000877299, ENST00000913746, ENST00000941388, ENST00000941389

RefSeq mRNA: 3 — MANE Select: NM_001272013 NM_001272012, NM_001272013, NM_033397

CCDS: CCDS7557

Canonical transcript exons

ENST00000337478 — 2 exons

Exon	Start	End
ENSE00001644973	104338246	104338465
ENSE00001690662	104309700	104316064

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 94.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.2154 / max 1162.7840, expressed in 1783 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111313	19.5624	1781
111312	1.6937	774
111314	0.7716	406
111311	0.1693	71
111307	0.0183	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	94.06	gold quality
lower esophagus mucosa	UBERON:0035834	93.64	gold quality
skin of leg	UBERON:0001511	93.23	gold quality
skin of abdomen	UBERON:0001416	93.13	gold quality
right atrium auricular region	UBERON:0006631	93.11	gold quality
bone marrow cell	CL:0002092	91.79	gold quality
cardiac atrium	UBERON:0002081	91.66	gold quality
right lung	UBERON:0002167	91.45	gold quality
popliteal artery	UBERON:0002250	91.38	gold quality
tibial artery	UBERON:0007610	91.38	gold quality
esophagus mucosa	UBERON:0002469	91.36	gold quality
upper lobe of left lung	UBERON:0008952	90.89	gold quality
mucosa of stomach	UBERON:0001199	90.62	gold quality
aorta	UBERON:0000947	90.10	gold quality
ectocervix	UBERON:0012249	90.02	gold quality
sural nerve	UBERON:0015488	89.84	gold quality
zone of skin	UBERON:0000014	89.42	gold quality
upper lobe of lung	UBERON:0008948	89.27	gold quality
omental fat pad	UBERON:0010414	89.26	gold quality
ascending aorta	UBERON:0001496	89.22	gold quality
peritoneum	UBERON:0002358	89.16	gold quality
blood	UBERON:0000178	89.04	gold quality
thoracic aorta	UBERON:0001515	88.80	gold quality
esophagus	UBERON:0001043	88.66	gold quality
heart left ventricle	UBERON:0002084	88.34	gold quality
embryo	UBERON:0000922	87.77	gold quality
ganglionic eminence	UBERON:0004023	87.77	gold quality
left coronary artery	UBERON:0001626	87.73	gold quality
leukocyte	CL:0000738	87.69	gold quality
adipose tissue of abdominal region	UBERON:0007808	87.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	21.32
E-ANND-3	yes	9.88

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

136 targeting ITPRIP, 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-5011-5P	100.00	83.46	5820
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6739-5P	99.80	67.87	2806

Literature-anchored findings (GeneRIF, showing 4)

• DANGER appears to allosterically modulate the sensitivity of IP(3) RtoCa(2+) inhibition, which likely alters IP(3)R-mediated Ca(2+) dynamics in cells where DANGER and IP(3)R are co-expressed (PMID:16990268)
• High DANGER expression is involved in high glucose-induced radioresistance through inhibiting DAPK-mediated anoikis in non-small cell lung cancer. (PMID:26769850)
• The suggested model of how long noncoding RNAs (lncI) TPRIP-1 orchestrates signal transduction for IFN production illustrates the essential role of lncRNAs in virus elimination. (PMID:29899107)
• ITPRIP promotes glioma progression by linking MYL9 to DAPK1 inhibition. (PMID:34111521)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	itprip	ENSDARG00000015576
danio_rerio	ITPRIP	ENSDARG00000036479
mus_musculus	Itprip	ENSMUSG00000117975
rattus_norvegicus	Itprip	ENSRNOG00000046036

Paralogs (9): CGAS (ENSG00000164430), MAB21L4 (ENSG00000172478), MAB21L3 (ENSG00000173212), MB21D2 (ENSG00000180611), MAB21L1 (ENSG00000180660), TMEM102 (ENSG00000181284), MAB21L2 (ENSG00000181541), ITPRIPL1 (ENSG00000198885), ITPRIPL2 (ENSG00000205730)

Protein

Protein identifiers

Inositol 1,4,5-trisphosphate receptor-interacting protein — Q8IWB1 (reviewed: Q8IWB1)

Alternative names: Protein DANGER

All UniProt accessions (2): Q8IWB1, X6RK76

UniProt curated annotations — full annotation on UniProt →

Function. Enhances Ca(2+)-mediated inhibition of inositol 1,4,5-triphosphate receptor (ITPR) Ca(2+) release.

Subunit / interactions. Interacts with ITPR.

Subcellular location. Cell membrane. Nucleus outer membrane.

Tissue specificity. Detected in brain where it is concentrated in cerebellar Purkinje cells (at protein level).

Similarity. Belongs to the ITPRIP family.

RefSeq proteins (3): NP_001258941, NP_001258942, NP_203755 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024810	MAB21L/cGLR	Family
IPR026250	ITPRIP-like	Family
IPR046906	Mab-21_HhH/H2TH-like	Domain

Pfam: PF20266

UniProt features (10 total): topological domain 2, glycosylation site 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1, coiled-coil region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWB1-F1	79.67	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 (1): 547

Glycosylation sites (2): 27, 80

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 200 (showing top): GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, BILD_HRAS_ONCOGENIC_SIGNATURE, GOBP_NEGATIVE_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_VIA_DEATH_DOMAIN_RECEPTORS, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_VIA_DEATH_DOMAIN_RECEPTORS, TGACATY_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_VIA_DEATH_DOMAIN_RECEPTORS, GOBP_NEGATIVE_REGULATION_OF_APOPTOTIC_SIGNALING_PATHWAY, SENESE_HDAC1_TARGETS_UP, CAGCCTC_MIR4855P, MILI_PSEUDOPODIA_CHEMOTAXIS_DN

GO Biological Process (4): extrinsic apoptotic signaling pathway via death domain receptors (GO:0008625), negative regulation of extrinsic apoptotic signaling pathway via death domain receptors (GO:1902042), signal transduction (GO:0007165), negative regulation of signal transduction (GO:0009968)

GO Molecular Function (2): protein kinase inhibitor activity (GO:0004860), protein binding (GO:0005515)

GO Cellular Component (4): nuclear outer membrane (GO:0005640), plasma membrane (GO:0005886), membrane (GO:0016020), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
extrinsic apoptotic signaling pathway	1
extrinsic apoptotic signaling pathway via death domain receptors	1
regulation of extrinsic apoptotic signaling pathway via death domain receptors	1
negative regulation of extrinsic apoptotic signaling pathway	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
protein kinase activity	1
kinase inhibitor activity	1
protein kinase regulator activity	1
binding	1
nuclear membrane	1
organelle outer membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
membrane	1
cell periphery	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

870 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITPRIP	ITPR3	Q14573	589
ITPRIP	ITPR1	Q14643	574
ITPRIP	RASSF3	Q86WH2	520
ITPRIP	RASSF5	Q8WWW0	507
ITPRIP	LSMEM1	Q8N8F7	488
ITPRIP	OSBPL2	Q9H1P3	446
ITPRIP	MDP1	Q86V88	445
ITPRIP	SLC75A1	Q14728	425
ITPRIP	IFI6	P09912	422
ITPRIP	TMX4	Q9H1E5	408
ITPRIP	ANO6	Q4KMQ2	403
ITPRIP	OR10H5	Q8NGA6	399
ITPRIP	MB21D2	Q8IYB1	387
ITPRIP	SLC4A7	Q9Y6M7	382
ITPRIP	CNNM4	Q6P4Q7	377

IntAct

96 interactions, top by confidence:

A	B	Type	Score
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
ITPRIP	PGRMC2	psi-mi:“MI:0915”(physical association)	0.670
PGRMC2	ITPRIP	psi-mi:“MI:0915”(physical association)	0.670
STK4	STRN	psi-mi:“MI:0914”(association)	0.610
ITPRIP	RASSF3	psi-mi:“MI:0915”(physical association)	0.560
ITPRIP	SGTB	psi-mi:“MI:0915”(physical association)	0.560
RASSF3	ITPRIP	psi-mi:“MI:0915”(physical association)	0.560
Rassf1	VAPB	psi-mi:“MI:0915”(physical association)	0.560
ITPRIP	NLGN3	psi-mi:“MI:0915”(physical association)	0.540
ITPRIP	NLGN3	psi-mi:“MI:0403”(colocalization)	0.540
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
CD1B	TOR1B	psi-mi:“MI:0914”(association)	0.530
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
NRROS	NDUFA3	psi-mi:“MI:0914”(association)	0.530
NCEH1	CLGN	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
RASSF1	MAP1B	psi-mi:“MI:0914”(association)	0.530
Hacd3	ITPRIP	psi-mi:“MI:0915”(physical association)	0.400
ITPRIP	Usp19	psi-mi:“MI:0915”(physical association)	0.400
ITPRIP	CACYBP	psi-mi:“MI:0915”(physical association)	0.400
PPP5C	ITPRIP	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (99): ITPRIP (Affinity Capture-MS), ITPRIP (Affinity Capture-MS), ITPRIP (Affinity Capture-MS), ITPRIP (Affinity Capture-MS), ITPRIP (Affinity Capture-MS), ITPRIP (Affinity Capture-MS), ITPRIP (Two-hybrid), ITPRIP (Affinity Capture-Western), ITPRIP (Affinity Capture-MS), ITPRIP (Affinity Capture-MS), ITPRIP (Affinity Capture-MS), ITPRIP (Affinity Capture-MS), ITPRIP (Affinity Capture-MS), ITPRIP (Affinity Capture-MS), ITPRIP (Affinity Capture-MS)

ESM2 similar proteins: A0JNQ6, A6NC42, A6NGQ2, A6NGR9, A6QP75, A7E3N7, A9X185, E1BDF2, E9PGG2, F6SZT2, P0C7A0, P85965, Q06VW1, Q0ZFW8, Q14DK4, Q3UK37, Q3UV16, Q3ZBN4, Q400G9, Q4VXA5, Q587J8, Q5JSQ8, Q60953, Q60I26, Q60I27, Q6NUI2, Q6ZUX3, Q810I0, Q8BH06, Q8C0R7, Q8IWB1, Q8IWY9, Q8IYX4, Q8K4C2, Q8N6L0, Q8N7F7, Q8NCV1, Q8TE82, Q91WA6, Q95JV3

Diamond homologs: A2ASA8, A7MB64, Q3TNL8, Q66H52, Q6GPH6, Q8IWB1, Q90XY5, Q567X9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	103
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

647 predictions. Top by Δscore:

Variant	Effect	Δscore
10:104316060:CTTTC:C	acceptor_gain	1.0000
10:104316061:TTTC:T	acceptor_gain	1.0000
10:104316065:C:CC	acceptor_gain	1.0000
10:104316065:CT:C	acceptor_loss	1.0000
10:104316066:T:C	acceptor_loss	1.0000
10:104316062:TTC:T	acceptor_gain	0.9900
10:104316063:TC:T	acceptor_gain	0.9900
10:104316064:CC:C	acceptor_gain	0.9900
10:104316072:C:CT	acceptor_gain	0.9800
10:104316065:C:T	acceptor_gain	0.9600
10:104316073:A:T	acceptor_gain	0.9600
10:104333678:T:A	donor_gain	0.9500
10:104333786:ACAG:A	donor_gain	0.9400
10:104333787:CAGC:C	donor_gain	0.9400
10:104333625:AC:A	donor_gain	0.9300
10:104333626:CC:C	donor_gain	0.9300
10:104332489:A:AC	donor_gain	0.9200
10:104332490:C:CC	donor_gain	0.9200
10:104331462:C:A	donor_gain	0.9100
10:104333634:T:TA	donor_gain	0.9000
10:104316061:TTTCC:T	acceptor_gain	0.8800
10:104316062:TTCC:T	acceptor_gain	0.8800
10:104316063:TCC:T	acceptor_gain	0.8800
10:104314506:T:TA	donor_gain	0.8700
10:104316064:CCT:C	acceptor_gain	0.8700
10:104316065:C:A	acceptor_gain	0.8700
10:104316066:T:A	acceptor_gain	0.8600
10:104326291:T:TA	donor_gain	0.8500
10:104333660:AGG:A	donor_gain	0.8500
10:104332491:T:C	donor_gain	0.8400

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000138883 (10:104330003 C>A), RS1000180583 (10:104325511 C>T), RS1000206992 (10:104324672 T>TA), RS1000234357 (10:104325803 A>C), RS1000333009 (10:104319002 A>G), RS1000403677 (10:104312779 A>G,T), RS1000460556 (10:104336515 G>A,C,T), RS1000486442 (10:104313587 G>A,C), RS1000584453 (10:104337421 G>A), RS1000636865 (10:104337885 G>A,T), RS1000747510 (10:104331542 A>G), RS1000977825 (10:104336382 C>T), RS1001004394 (10:104314129 T>A,C), RS1001008238 (10:104319814 C>G), RS1001240667 (10:104327067 G>A,T)

Disease associations

OMIM: gene MIM:620205 | 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
GCST90002395_35	Mean platelet volume	6.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression, affects expression, increases abundance	4
Valproic Acid	affects cotreatment, increases expression, decreases expression	4
Estradiol	affects cotreatment, increases expression	3
potassium chromate(VI)	increases expression, decreases expression, affects cotreatment	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression	2
Benzo(a)pyrene	increases methylation, affects methylation, increases expression	2
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
Asbestos, Crocidolite	affects expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
ginger extract	increases abundance, affects cotreatment, affects expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
dodecyldimethylamine oxide	increases expression	1
beta-lapachone	increases expression	1
afimoxifene	increases expression, affects reaction	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
didecyldimethylammonium	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1

Clinical trials (associated diseases)

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