IRAG2

Summary

IRAG2 (inositol 1,4,5-triphosphate receptor associated 2, HGNC:6690) is a protein-coding gene on chromosome 12p12.1, encoding Inositol 1,4,5-triphosphate receptor associated 2 (Q12912). Plays a role in the delivery of peptides to major histocompatibility complex (MHC) class I molecules; this occurs in a transporter associated with antigen processing (TAP)-independent manner.

The protein encode dby this gene is expressed in a developmentally regulated manner in lymphoid cell lines and tissues. The protein is localized to the cytoplasmic face of the endoplasmic reticulum.

Source: NCBI Gene 4033 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 76 total
• MANE Select transcript: NM_001366544

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6690
Approved symbol	IRAG2
Name	inositol 1,4,5-triphosphate receptor associated 2
Location	12p12.1
Locus type	gene with protein product
Status	Approved
Aliases	JAW1
Ensembl gene	ENSG00000118308
Ensembl biotype	protein_coding
OMIM	602003
Entrez	4033

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 18 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000354454, ENST00000361433, ENST00000536173, ENST00000547044, ENST00000548766, ENST00000549437, ENST00000550945, ENST00000553398, ENST00000554272, ENST00000554942, ENST00000555141, ENST00000555165, ENST00000555194, ENST00000555877, ENST00000555885, ENST00000556485, ENST00000556887, ENST00000557270, ENST00000557472, ENST00000557489, ENST00000636465, ENST00000878408, ENST00000878409, ENST00000878410, ENST00000878411, ENST00000940909, ENST00000940910, ENST00000940911, ENST00000940912

RefSeq mRNA: 14 — MANE Select: NM_001366544 NM_001204126, NM_001204127, NM_001366540, NM_001366541, NM_001366542, NM_001366543, NM_001366544, NM_001366545, NM_001366546, NM_001366547, NM_001366548, NM_001366549, NM_001394803, NM_006152

CCDS: CCDS8701, CCDS91664

Canonical transcript exons

ENST00000556887 — 22 exons

Exon	Start	End
ENSE00001406179	25063720	25063816
ENSE00001407703	25062820	25062900
ENSE00002362489	25061592	25061653
ENSE00002403620	25066365	25066512
ENSE00002517447	25052706	25052956
ENSE00003463110	25104009	25104058
ENSE00003526335	25102198	25102241
ENSE00003538262	25069350	25069431
ENSE00003538706	25096910	25097044
ENSE00003558500	25079244	25079290
ENSE00003559267	25090057	25090197
ENSE00003575853	25079656	25079763
ENSE00003588023	25104361	25104462
ENSE00003590583	25106943	25107050
ENSE00003593325	25088100	25088157
ENSE00003622257	25089614	25089677
ENSE00003646121	25089763	25089790
ENSE00003650788	25103837	25103899
ENSE00003651018	25083423	25083493
ENSE00003673681	25101178	25101325
ENSE00003676826	25079398	25079462
ENSE00003928866	25107817	25108335

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 98.04.

FANTOM5 (CAGE): breadth broad, TPM avg 16.3602 / max 5559.8335, expressed in 560 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124762	6.6492	429
124760	5.3667	401
124763	1.5035	241
124756	1.3390	225
124761	0.6163	122
124764	0.3175	106
206651	0.1440	62
124759	0.0747	17
124771	0.0701	34
124758	0.0697	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.04	gold quality
vermiform appendix	UBERON:0001154	96.49	gold quality
monocyte	CL:0000576	96.46	gold quality
mononuclear cell	CL:0000842	96.30	gold quality
leukocyte	CL:0000738	96.23	gold quality
blood	UBERON:0000178	95.82	gold quality
lymph node	UBERON:0000029	95.79	gold quality
oocyte	CL:0000023	95.61	gold quality
granulocyte	CL:0000094	95.52	gold quality
bone marrow	UBERON:0002371	95.26	gold quality
spleen	UBERON:0002106	95.05	gold quality
epithelium of nasopharynx	UBERON:0001951	94.84	gold quality
caecum	UBERON:0001153	94.08	gold quality
bone marrow cell	CL:0002092	93.90	gold quality
thymus	UBERON:0002370	92.48	gold quality
right uterine tube	UBERON:0001302	92.30	gold quality
body of pancreas	UBERON:0001150	91.83	gold quality
mucosa of urinary bladder	UBERON:0001259	90.35	gold quality
tonsil	UBERON:0002372	89.28	gold quality
colonic epithelium	UBERON:0000397	88.69	gold quality
palpebral conjunctiva	UBERON:0001812	88.53	gold quality
trabecular bone tissue	UBERON:0002483	88.00	gold quality
pharyngeal mucosa	UBERON:0000355	87.73	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.46	gold quality
diaphragm	UBERON:0001103	86.99	gold quality
rectum	UBERON:0001052	86.36	gold quality
right lung	UBERON:0002167	86.09	gold quality
urethra	UBERON:0000057	86.02	gold quality
small intestine	UBERON:0002108	85.87	gold quality
mucosa of transverse colon	UBERON:0004991	84.69	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-75688	yes	3104.44
E-MTAB-8410	yes	2480.77
E-MTAB-9906	yes	2014.72
E-GEOD-125970	yes	742.22
E-CURD-122	yes	20.19
E-ANND-3	yes	13.24
E-CURD-114	yes	7.70
E-MTAB-6075	no	1484.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting IRAG2, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-5000-5P	97.40	66.11	1055
HSA-MIR-600	97.07	66.73	1259

Literature-anchored findings (GeneRIF, showing 3)

• Clinical variability and probable founder effect in oculocutaneous albinism type 7. (PMID:31694064)
• Jaw1/LRMP increases Ca(2+) influx upon GPCR stimulation with heterogeneous effect on the activity of each ITPR subtype. (PMID:35676525)
• Jaw1/LRMP is associated with the maintenance of Golgi ribbon structure. (PMID:36689741)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrmp	ENSDARG00000045574
mus_musculus	Irag2	ENSMUSG00000030263
rattus_norvegicus	Irag2	ENSRNOG00000029308

Paralogs (1): IRAG1 (ENSG00000072952)

Protein

Protein identifiers

Inositol 1,4,5-triphosphate receptor associated 2 — Q12912 (reviewed: Q12912)

Alternative names: Lymphoid-restricted membrane protein, Protein Jaw1

All UniProt accessions (11): A0A0G2JL87, A0A1B0GU45, Q12912, F5H006, F8VRE4, F8W9L6, G3V2F6, G3V3C2, G3V513, H0YJ39, H0YJC6

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the delivery of peptides to major histocompatibility complex (MHC) class I molecules; this occurs in a transporter associated with antigen processing (TAP)-independent manner. May play a role in taste signal transduction via ITPR3. May play a role during fertilization in pronucleus congression and fusion. Plays a role in maintaining nuclear shape, maybe as a component of the LINC complex and through interaction with microtubules. Plays a role in the regulation of cellular excitability by regulating the hyperpolarization-activated cyclic nucleotide-gated HCN4 channel activity.

Subunit / interactions. Interacts (via coiled-coil domain) with ITPR3. Interacts with SUN1 and SUN2. Interacts with microtubules. Interacts with HCN4; regulates HCN4 channel activity.

Subcellular location. Cytoplasm Endoplasmic reticulum membrane. Nucleus envelope. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle pole. Chromosome.

Tissue specificity. Expressed at high levels in pre B-cells, mature B-cells and pre T-cells. Expressed at low levels in mature T-cells and plasma B-cells. Expressed in germinal center B-cells, splenic marginal zone cells and B-cell lymphomas. Expressed in neuronal cells in the cerebral cortex, epithelial cells in tonsil, adrenal glands, zymogen-producing cells in the stomach and epithelial cells in seminal vesicles.

Post-translational modifications. The removal of the C-terminal lumenal domain occurs by proteolytic processing.

Similarity. Belongs to the IRAG2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q12912-1	1	yes
Q12912-2	2

RefSeq proteins (14): NP_001191055, NP_001191056, NP_001353469, NP_001353470, NP_001353471, NP_001353472, NP_001353473, NP_001353474, NP_001353475, NP_001353476, NP_001353477, NP_001353478, NP_001381732, NP_006143 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008677	MRVI1	Family

Pfam: PF05781

UniProt features (26 total): modified residue 4, sequence variant 4, compositionally biased region 3, region of interest 3, chain 2, topological domain 2, sequence conflict 2, helix 2, splice variant 1, strand 1, transmembrane region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8B46	X-RAY DIFFRACTION	1.67
8B5X	X-RAY DIFFRACTION	1.98
7Z8Y	X-RAY DIFFRACTION	2.29

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12912-F1	58.72	0.25

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 (4): 91, 363, 370, 424

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 298 (showing top): GOBP_SINGLE_FERTILIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_VESICLE_LOCALIZATION, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, MODULE_45, MODULE_64, GOBP_MEMBRANE_FUSION, GOBP_VESICLE_TARGETING, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_MICROTUBULE_ORGANIZING_CENTER, MODULE_118, GOBP_ORGANELLE_MEMBRANE_FUSION, GOBP_NUCLEUS_ORGANIZATION

GO Biological Process (5): immune system process (GO:0002376), obsolete vesicle targeting (GO:0006903), vesicle fusion (GO:0006906), nucleus organization (GO:0006997), single fertilization (GO:0007338)

GO Molecular Function (2): microtubule binding (GO:0008017), protein binding (GO:0005515)

GO Cellular Component (12): spindle pole (GO:0000922), nuclear envelope (GO:0005635), chromosome (GO:0005694), endoplasmic reticulum membrane (GO:0005789), centrosome (GO:0005813), plasma membrane (GO:0005886), membrane (GO:0016020), azurophil granule membrane (GO:0035577), nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
endomembrane system	2
intracellular membraneless organelle	2
intracellular membrane-bounded organelle	2
biological_process	1
vesicle organization	1
vesicle-mediated transport	1
organelle membrane fusion	1
organelle organization	1
fertilization	1
tubulin binding	1
binding	1
spindle	1
nucleus	1
organelle envelope	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
centriole	1
microtubule organizing center	1
membrane	1
cell periphery	1
lysosomal membrane	1
secretory granule membrane	1
azurophil granule	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1244 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IRAG2	KASH5	Q8N6L0	696
IRAG2	SYNE4	Q8N205	624
IRAG2	LMNTD1	Q8N9Z9	543
IRAG2	DNAI7	Q6TDU7	542
IRAG2	SH2D7	A6NKC9	519
IRAG2	SUN3	Q8TAQ9	481
IRAG2	SYNE2	Q8WXH0	475
IRAG2	SUN1	O94901	468
IRAG2	SYNE1	Q8NF91	461
IRAG2	ETFRF1	Q6IPR1	446
IRAG2	VGLL4	Q14135	440
IRAG2	SUN5	Q8TC36	430
IRAG2	SUN2	Q9UH99	420
IRAG2	BCAT1	P54687	419
IRAG2	SYNE3	Q6ZMZ3	415

IntAct

16 interactions, top by confidence:

A	B	Type	Score
SUN1	IRAG2	psi-mi:“MI:0407”(direct interaction)	0.620
IRAG2	SUN1	psi-mi:“MI:0407”(direct interaction)	0.620
SUN2	IRAG2	psi-mi:“MI:0407”(direct interaction)	0.440
IRAG2	CORO1C	psi-mi:“MI:0915”(physical association)	0.400
EPHA1	PIK3R2	psi-mi:“MI:2364”(proximity)	0.270
	IRAG2	psi-mi:“MI:0915”(physical association)	0.000
IRAG2		psi-mi:“MI:0915”(physical association)	0.000
IRAG2	chdC	psi-mi:“MI:0915”(physical association)	0.000
YWHAE	IRAG2	psi-mi:“MI:0915”(physical association)	0.000
IRAG2	WNK1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): LRMP (Affinity Capture-MS), LRMP (Affinity Capture-MS), LRMP (Proximity Label-MS), LRMP (Protein-RNA), CORO1C (Proximity Label-MS), LRMP (Affinity Capture-MS), LRMP (Affinity Capture-MS), LRMP (Proximity Label-MS), LRMP (Affinity Capture-MS), LRMP (Proximity Label-MS), LRMP (Affinity Capture-RNA), LRMP (Proximity Label-MS), LRMP (Proximity Label-MS), LRMP (Proximity Label-MS), LRMP (Proximity Label-MS)

ESM2 similar proteins: A0A140LFM6, A0A1B0GVH6, A0A1L8H8C0, A0A2K1JJ00, A0JMD2, A2ARZ3, A2AWL7, A4IGV6, A6H5Y1, D3ZJ47, E9Q309, F1QPR4, F5H4B4, H0WFA5, O14513, O35413, O94875, P0CAX8, P48437, Q12912, Q15468, Q1LXZ9, Q1X8D7, Q28FG2, Q3UTJ2, Q3ZBS1, Q499E5, Q49A88, Q4V7H1, Q5T5U3, Q5VT06, Q62417, Q62770, Q69Z38, Q6DFB0, Q80TY4, Q8BLN6, Q8CB14, Q8IWI9, Q8K0T7

Diamond homologs: Q12912, Q5RHB5, Q60664, Q9N1F0, Q9WUX5, Q9Y6F6, Q2T9R2, Q80VJ8, Q8N6L0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2984 predictions. Top by Δscore:

Variant	Effect	Δscore
12:25063718:A:AG	acceptor_gain	1.0000
12:25063719:G:GG	acceptor_gain	1.0000
12:25063815:GG:G	donor_gain	1.0000
12:25063816:GG:G	donor_gain	1.0000
12:25066513:G:GG	donor_gain	1.0000
12:25069432:G:GG	donor_gain	1.0000
12:25079392:TGGCA:T	acceptor_loss	1.0000
12:25079393:GGCA:G	acceptor_loss	1.0000
12:25079394:GCA:G	acceptor_loss	1.0000
12:25079395:CA:C	acceptor_loss	1.0000
12:25079396:A:AG	acceptor_gain	1.0000
12:25079396:AG:A	acceptor_gain	1.0000
12:25079396:AGGGA:A	acceptor_loss	1.0000
12:25079397:G:GC	acceptor_loss	1.0000
12:25079397:G:GG	acceptor_gain	1.0000
12:25079397:GG:G	acceptor_gain	1.0000
12:25079397:GGGA:G	acceptor_gain	1.0000
12:25079460:GTG:G	donor_gain	1.0000
12:25079461:TGG:T	donor_loss	1.0000
12:25079463:G:GA	donor_loss	1.0000
12:25079464:T:A	donor_loss	1.0000
12:25088154:GGAG:G	donor_gain	1.0000
12:25088155:GAGG:G	donor_gain	1.0000
12:25089678:G:GG	donor_gain	1.0000
12:25089761:A:AG	acceptor_gain	1.0000
12:25089762:G:GA	acceptor_gain	1.0000
12:25089762:GC:G	acceptor_gain	1.0000
12:25096908:A:AG	acceptor_gain	1.0000
12:25096909:G:GG	acceptor_gain	1.0000
12:25101172:T:A	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000043128 (12:25002447 A>G), RS1000067516 (12:25096527 G>A), RS1000115510 (12:25054676 G>A), RS1000126534 (12:25083644 G>C), RS1000135704 (12:25034135 G>A), RS1000165330 (12:25066046 C>T), RS1000195336 (12:25066362 C>T), RS1000256203 (12:25019795 C>G), RS1000285866 (12:25007479 G>A), RS1000344088 (12:25078337 G>C), RS1000369505 (12:25089266 A>G), RS1000382780 (12:25025625 T>C), RS1000459170 (12:25066905 C>T), RS1000510208 (12:25026816 A>G), RS1000549627 (12:25054442 C>T)

Disease associations

OMIM: gene MIM:602003 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, increases expression	3
Benzo(a)pyrene	increases expression, increases methylation	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
bisphenol F	increases expression	1
bisphenol A	affects expression	1
arsenite	increases methylation	1
bisphenol B	increases expression	1
ON 01910	affects expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants, Occupational	affects expression	1
Cadmium	decreases expression, increases abundance	1
Carmustine	decreases expression	1
Cisplatin	increases expression	1
Curcumin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Nickel	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Silicon Dioxide	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1898	U-2973	Cancer cell line	Male

Clinical trials (associated diseases)

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