CIRBP

Summary

CIRBP (cold inducible RNA binding protein, HGNC:1982) is a protein-coding gene on chromosome 19p13.3, encoding Cold-inducible RNA-binding protein (Q14011). Cold-inducible mRNA binding protein that plays a protective role in the genotoxic stress response by stabilizing transcripts of genes involved in cell survival.

Enables mRNA 3’-UTR binding activity and small ribosomal subunit rRNA binding activity. Involved in mRNA stabilization; positive regulation of translation; and response to UV. Located in cytoplasm and nucleoplasm.

Source: NCBI Gene 1153 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_001300829

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1982
Approved symbol	CIRBP
Name	cold inducible RNA binding protein
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	CIRP
Ensembl gene	ENSG00000099622
Ensembl biotype	protein_coding
OMIM	602649
Entrez	1153

Gene structure

Transcript identifiers

Ensembl transcripts: 56 — 31 protein_coding, 13 nonsense_mediated_decay, 11 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000320936, ENST00000413636, ENST00000444172, ENST00000585630, ENST00000585913, ENST00000585914, ENST00000586472, ENST00000586548, ENST00000586555, ENST00000586636, ENST00000586773, ENST00000587169, ENST00000587323, ENST00000587896, ENST00000588030, ENST00000588090, ENST00000588230, ENST00000588344, ENST00000588411, ENST00000588917, ENST00000589161, ENST00000589235, ENST00000589266, ENST00000589686, ENST00000589710, ENST00000590171, ENST00000590188, ENST00000590347, ENST00000590704, ENST00000591055, ENST00000591097, ENST00000591376, ENST00000591622, ENST00000591659, ENST00000591935, ENST00000592051, ENST00000592234, ENST00000592412, ENST00000592467, ENST00000592815, ENST00000593048, ENST00000593093, ENST00000593128, ENST00000593283, ENST00000621399, ENST00000628979, ENST00000908650, ENST00000908651, ENST00000908652, ENST00000916895, ENST00000916896, ENST00000916897, ENST00000916898, ENST00000952605, ENST00000952606, ENST00000952607

RefSeq mRNA: 3 — MANE Select: NM_001300829 NM_001280, NM_001300815, NM_001300829

CCDS: CCDS12059, CCDS74244, CCDS74245

Canonical transcript exons

ENST00000587896 — 6 exons

Exon	Start	End
ENSE00002284955	1269332	1269410
ENSE00003501315	1270928	1271036
ENSE00003581600	1271329	1271467
ENSE00003619232	1271140	1271246
ENSE00003625670	1271551	1271632
ENSE00003842494	1271981	1274810

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 250.3245 / max 1379.3749, expressed in 1827 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172930	246.6478	1827
172929	1.0550	568
172933	1.0491	521
172934	0.8662	432
208630	0.4985	293
172935	0.2080	93

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.76	gold quality
corpus epididymis	UBERON:0004359	99.74	gold quality
caput epididymis	UBERON:0004358	99.73	gold quality
parietal pleura	UBERON:0002400	99.71	gold quality
germinal epithelium of ovary	UBERON:0001304	99.70	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.70	gold quality
right uterine tube	UBERON:0001302	99.69	gold quality
cerebellar cortex	UBERON:0002129	99.68	gold quality
cerebellar hemisphere	UBERON:0002245	99.68	gold quality
pituitary gland	UBERON:0000007	99.63	gold quality
adenohypophysis	UBERON:0002196	99.63	gold quality
middle temporal gyrus	UBERON:0002771	99.61	gold quality
left ovary	UBERON:0002119	99.60	gold quality
ventricular zone	UBERON:0003053	99.60	gold quality
endothelial cell	CL:0000115	99.59	gold quality
ovary	UBERON:0000992	99.59	gold quality
mucosa of stomach	UBERON:0001199	99.58	gold quality
palpebral conjunctiva	UBERON:0001812	99.58	gold quality
paraflocculus	UBERON:0005351	99.56	gold quality
mammary duct	UBERON:0001765	99.55	gold quality
pigmented layer of retina	UBERON:0001782	99.55	gold quality
cerebellum	UBERON:0002037	99.55	gold quality
right ovary	UBERON:0002118	99.55	gold quality
ganglionic eminence	UBERON:0004023	99.55	gold quality
endocervix	UBERON:0000458	99.54	gold quality
seminal vesicle	UBERON:0000998	99.54	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.53	gold quality
right lobe of thyroid gland	UBERON:0001119	99.52	gold quality
thyroid gland	UBERON:0002046	99.52	gold quality
visceral pleura	UBERON:0002401	99.52	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	76.82
E-HCAD-10	yes	45.67
E-CURD-122	yes	36.51
E-GEOD-135922	yes	26.80
E-CURD-46	yes	20.35
E-GEOD-125970	yes	12.77
E-MTAB-10042	yes	12.14
E-CURD-112	yes	5.62
E-MTAB-9154	no	1950.07
E-MTAB-8205	no	876.01
E-MTAB-6108	no	808.87
E-MTAB-10283	no	668.28
E-MTAB-11268	no	406.74
E-HCAD-6	no	34.48
E-MTAB-10287	no	21.44

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1

miRNA regulators (miRDB)

25 targeting CIRBP, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-4691-3P	98.11	66.83	1204
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-383-5P	96.86	67.55	820
HSA-MIR-4301	95.00	65.22	554
HSA-MIR-3610	93.97	64.11	73

Literature-anchored findings (GeneRIF, showing 40)

• results suggest that cold inducible RNA binding protein may participate in the cell cycle regulation of normal endometrium and the loss of its expression may be involved in endometrial carcinogenesis (PMID:12819390)
• RBM3 and CIRP are adaptatively expressed in response to hypoxia by a mechanism that involves neither HIF-1 nor mitochondria (PMID:15075239)
• CIRP enhanced extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation, and treatment with an MEK inhibitor decreased the proliferation caused by CIRP. (PMID:19158277)
• pharmacological modulation of RBM3 and CIRBP may represent novel therapeutic approaches for prostate cancer. (PMID:19277990)
• CIRBP contributes to ultraviolet light- and lipopolysaccharide-induced expression of IL1beta by regulating NFkappaB activity. (PMID:23437386)
• CIRBP regulates the expression of interleukin-1beta in an NF-kappaB-dependent fashion. (PMID:23437386)
• report increased levels of cold-inducible RNA-binding protein (CIRP) in the blood of individuals admitted to the surgical intensive care unit with hemorrhagic shock (PMID:24097189)
• High levels of CIRP protein expression was associated with a short survival rate in oral squamous cell carcinoma patients. (PMID:25027624)
• Cirp promotes the development of intestinal inflammation and colorectal tumors through regulating apoptosis and production of TNFalpha and IL23 in inflammatory cells. (PMID:25187386)
• The expression of CIRP in pituitary adenoma is closely related with tumor proliferation and invasion, and its significantly elevated expression level indicates post-op recurrence. (PMID:25934796)
• CIRP inhibits DNA damage-induced apoptosis by regulating p53 protein.CIRP suppresses p53 upregulation during apoptosis.CIRP regulates the expression of genes involved in apoptosis. (PMID:26188505)
• Study shows that CIRP elevated plasma concentration is significantly associated with poor prognosis among patients with sepsis. Therefore, CIRP is a potential predictor of sepsis prognosis. (PMID:26361390)
• CIRP protein regulates telomerase activity in a temperature-dependent manner by regulating the level of TERT mRNAs. (PMID:26673712)
• Clinically, CIRP overexpression is significantly correlated with Cushing’s disease recurrence. CIRP appears to play a critical tumorigenesis function in Cushing’s disease and its expression might be a useful biomarker for tumor recurrence. (PMID:26824322)
• hnRNP A18 can promote tumor growth in in vivo models by coordinating the translation of pro-survival transcripts to support the demands of proliferating cells and increase survival under cellular stress. (PMID:26824423)
• In human abdominal aortic aneurysm (AAA) tissue, Cold-inducible RNA-binding protein (CIRP) exhibited a 5.6-fold and 93% increase in mRNA and protein expression, respectively. In a rat AAA model, CIRP was upregulated significantly in a time-dependent manner in the serum and AAA tissue. (PMID:26936526)
• CIRP was expressed in the bronchi of human COPD patients and was involved in inflammatory factors and MUC5AC expression after cold stimulation through the ERK and NF-kappaB pathways (PMID:27184164)
• The serum and synovial concentrations of CIRP in the rheumatoid arthritis patients were increased, suggesting that CIRP mediates inflammation and is a potential marker for synovial inflammation. (PMID:27315340)
• We found out that the link between CIRP and Snail is mediated by ERK and p38 pathways. EMT is a critical component of carcinoma metastasis and invasion. As demonstrated in this study, the biological role of CIRP in EMT may explain why CIRP overexpression has been associated with a bad prognosis in cancer patients. (PMID:27395339)
• this study shows that CIRP expression in bronchial airway epithelial cells of patients with chronic obstructive pulmonary disease is higher than that in healthy person (PMID:27423012)
• cold temperature can induce an airway inflammatory response and excess mucus production via a CIRP-mediated increase in mRNA stability and protein translation (PMID:27477308)
• We generated a transgenic mouse model overexpressing human CIRP in the mammary epithelium to ask if it plays a role in mammary gland development. Effects of CIRP overexpression on mammary gland morphology, cell proliferation, and apoptosis were studied from puberty through pregnancy, lactation and weaning (PMID:27837912)
• Increased synovial fluid CIRP concentrations were closely associated with the severity of knee osteoarthritis (PMID:27840101)
• CIRP Expression Is Induced in Skin Cancer Cells and in Keratinocytes Exposed to Lower-Dose But Not Higher-Dose UVB Radiation. (PMID:27864909)
• Crystal structure of the hnRNP A18 RNA recognition motif has been reported. (PMID:28368279)
• Low CIRP expression is associated with colon Cancer. (PMID:28373441)
• Cold induction of serine and arginine rich splicing factor 5 (SRSF5) is independent of cold-inducible RNA-binding protein (CIRP) and RNA-binding motif protein 3 (RBM3). (PMID:28536481)
• This study reports that cold-inducible RNA-binding protein (CIRBP) is a newly identified key regulator in DNA double-strand break (DSB) repair. (PMID:29432179)
• CIRP mediates the activation of STAT3-Bag-1 signaling cascade via activating the Janus kinase family proteins and NF-kappaB signaling pathways upon UV irradiation. (PMID:29981150)
• CIRBP could be a novel oncogene in human bladder cancer inducing transcription of HIF-1alpha. (PMID:30315244)
• Compared with pre-operation levels, CIRP levels significantly increased 6 h after cardiovascular surgery with CPB. Multiple linear regression analysis showed that the length of CPB time contributed to CIRP production (P=0.013). (PMID:31054221)
• downregulation of CIRP may render cardiac cells prone to apoptosis in heart failure. (PMID:31405566)
• Extracellular CIRP as an endogenous TREM-1 ligand to fuel inflammation in sepsis. (PMID:32027618)
• Cold-inducible RNA-binding protein might determine the severity and the presences of major/minor criteria for severe community-acquired pneumonia and best predicted mortality. (PMID:32689999)
• Cold-inducible RNA binding protein promotes breast cancer cell malignancy by regulating Cystatin C levels. (PMID:33172965)
• CIRP Sensitizes Cancer Cell Responses to Ionizing Radiation. (PMID:33429432)
• Human antigen R (HuR) and Cold inducible RNA-binding protein (CIRP) influence intestinal mucosal barrier function in ulcerative colitis by competitive regulation on Claudin1. (PMID:33638934)
• Cold-inducible RNA-binding protein (CIRP) potentiates uric acid-induced IL-1beta production. (PMID:33902703)
• ATP regulates RNA-driven cold inducible RNA binding protein phase separation. (PMID:33991007)
• CIRP Secretion during Cardiopulmonary Bypass Is Associated with Increased Risk of Postoperative Acute Kidney Injury. (PMID:34233365)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cirbp	ENSMUSG00000045193
rattus_norvegicus		ENSRNOG00000088478

Paralogs (36): DAZAP1 (ENSG00000071626), RBM23 (ENSG00000100461), RBM3 (ENSG00000102317), NCL (ENSG00000115053), TIA1 (ENSG00000116001), HNRNPA2B1 (ENSG00000122566), RBM19 (ENSG00000122965), RBM39 (ENSG00000131051), MSI1 (ENSG00000135097), HNRNPA1 (ENSG00000135486), HNRNPD (ENSG00000138668), HNRNPA1L2 (ENSG00000139675), RBMX (ENSG00000147274), A1CF (ENSG00000148584), TIAL1 (ENSG00000151923), RBM46 (ENSG00000151962), HNRNPDL (ENSG00000152795), MSI2 (ENSG00000153944), RBM47 (ENSG00000163694), RBMY1F (ENSG00000169800), HNRNPA3 (ENSG00000170144), RBMXL2 (ENSG00000170748), RBM4B (ENSG00000173914), RBM4 (ENSG00000173933), RBMXL3 (ENSG00000175718), HNRNPA0 (ENSG00000177733), TRNAU1AP (ENSG00000180098), HNRNPAB (ENSG00000197451), RBMXL1 (ENSG00000213516), HNRNPA1L3 (ENSG00000224578), RBMY1J (ENSG00000226941), RBMY1A1 (ENSG00000234414), RBMY1E (ENSG00000242389), RBMY1B (ENSG00000242875), RBMY1D (ENSG00000244395), DND1 (ENSG00000256453)

Protein

Protein identifiers

Cold-inducible RNA-binding protein — Q14011 (reviewed: Q14011)

Alternative names: A18 hnRNP, Glycine-rich RNA-binding protein CIRP

All UniProt accessions (17): Q14011, D6W5Y5, F6WMK9, K7EIF7, K7EJV1, K7EJV5, K7ELL4, K7ELT6, K7ELV6, K7EMY9, K7ENN6, K7ENX8, K7EPM4, K7EQL0, K7EQR7, K7EQX4, Q53XX5

UniProt curated annotations — full annotation on UniProt →

Function. Cold-inducible mRNA binding protein that plays a protective role in the genotoxic stress response by stabilizing transcripts of genes involved in cell survival. Acts as a translational activator. Seems to play an essential role in cold-induced suppression of cell proliferation. Binds specifically to the 3’-untranslated regions (3’-UTRs) of stress-responsive transcripts RPA2 and TXN. Acts as a translational repressor. Promotes assembly of stress granules (SGs), when overexpressed.

Subunit / interactions. Interacts with EIF4G1. Associates with ribosomes.

Subcellular location. Nucleus. Nucleoplasm. Cytoplasm.

Tissue specificity. Ubiquitous.

Post-translational modifications. Methylated on arginine residues. Methylation of the RGG motifs is a prerequisite for recruitment into SGs. Phosphorylated by CK2, GSK3A and GSK3B. Phosphorylation by GSK3B increases RNA-binding activity to the TXN 3’-UTR transcript upon exposure to UV radiation.

Domain organisation. Both the RRM domain and the arginine, glycine (RGG) rich domain are necessary for binding to the TXN 3’-untranslated region. Both the RRM domain and the arginine, glycine (RGG) rich domain (RGG repeats) are necessary for optimal recruitment into SGs upon cellular stress. The C-terminal domain containing RGG repeats is necessary for translational repression.

Induction. By cold stress in response to DNA damage induced by UV irradiation or UV mimetic agents. Up-regulated by hypoxia.

Isoforms (3)

UniProt ID	Names	Canonical?
Q14011-1	1	yes
Q14011-2	2
Q14011-3	3

RefSeq proteins (3): NP_001271, NP_001287744, NP_001287758* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR003954	RRM_euk-type	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034278	RBM3/CIRBP_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR050441	RBM	Family

Pfam: PF00076

UniProt features (25 total): modified residue 6, strand 4, helix 4, splice variant 3, compositionally biased region 3, turn 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5TBX	X-RAY DIFFRACTION	1.77
8CMK	X-RAY DIFFRACTION	2.94
1X5S	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14011-F1	61.78	0.00

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 (6): 159, 163, 130, 138, 146, 156

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 291 (showing top): WANG_CLIM2_TARGETS_UP, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_DN, GOBP_RESPONSE_TO_COLD, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, HSIAO_HOUSEKEEPING_GENES, CHANDRAN_METASTASIS_DN, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOMF_TRANSLATION_REGULATOR_ACTIVITY, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP

GO Biological Process (7): response to cold (GO:0009409), response to UV (GO:0009411), stress granule assembly (GO:0034063), positive regulation of translation (GO:0045727), positive regulation of mRNA splicing, via spliceosome (GO:0048026), mRNA stabilization (GO:0048255), negative regulation of translation (GO:0017148)

GO Molecular Function (6): RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), translation repressor activity (GO:0030371), small ribosomal subunit rRNA binding (GO:0070181), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), cytoplasm (GO:0005737), cytoplasmic stress granule (GO:0010494)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translation	2
regulation of translation	2
binding	2
cellular anatomical structure	2
response to stress	1
response to temperature stimulus	1
response to light stimulus	1
membraneless organelle assembly	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
mRNA splicing, via spliceosome	1
positive regulation of RNA splicing	1
regulation of mRNA splicing, via spliceosome	1
positive regulation of mRNA processing	1
regulation of mRNA stability	1
RNA stabilization	1
negative regulation of mRNA catabolic process	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
nucleic acid binding	1
mRNA binding	1
negative regulation of translation	1
translation regulator activity	1
rRNA binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
intracellular anatomical structure	1
cytoplasmic ribonucleoprotein granule	1

Protein interactions and networks

STRING

2808 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CIRBP	TLR4	O00206	845
CIRBP	TREM1	Q9NP99	726
CIRBP	LY96	Q9Y6Y9	656
CIRBP	KHDRBS1	Q07666	581
CIRBP	PER3	P56645	567
CIRBP	YBX1	P16990	546
CIRBP	EIF4G1	Q04637	544
CIRBP	TXN	P10599	517
CIRBP	HNRNPL	P14866	493
CIRBP	FAM174C	Q9BVV8	484
CIRBP	FUS	P35637	478
CIRBP	RIOK3	O14730	463
CIRBP	JUN	P05412	459
CIRBP	CALM1	P02593	450
CIRBP	EGR1	P18146	447

IntAct

206 interactions, top by confidence:

A	B	Type	Score
CIRBP	HNRNPK	psi-mi:“MI:0915”(physical association)	0.800
HNRNPK	CIRBP	psi-mi:“MI:0915”(physical association)	0.800
TNPO3	CIRBP	psi-mi:“MI:0407”(direct interaction)	0.740
SNRPA	CIRBP	psi-mi:“MI:0915”(physical association)	0.670
CIRBP	RBMX	psi-mi:“MI:0915”(physical association)	0.670
KHDRBS2	CIRBP	psi-mi:“MI:0915”(physical association)	0.670
CIRBP	KHDRBS2	psi-mi:“MI:0915”(physical association)	0.670
RBMX	CIRBP	psi-mi:“MI:0915”(physical association)	0.670
CIRBP	SNRPA	psi-mi:“MI:0915”(physical association)	0.670
ATXN1	CIRBP	psi-mi:“MI:0915”(physical association)	0.670
PLK1	EVI5	psi-mi:“MI:0914”(association)	0.660
CIRBP	PSPH	psi-mi:“MI:0915”(physical association)	0.570
CIRBP	RBMY1A1	psi-mi:“MI:0915”(physical association)	0.560
CIRBP	RBMY1F	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (210): HNRNPK (Two-hybrid), RBMY1A1 (Two-hybrid), SNRPA (Two-hybrid), RBMX (Two-hybrid), LNX1 (Two-hybrid), RBMY1F (Two-hybrid), KHDRBS2 (Two-hybrid), CIRBP (Affinity Capture-RNA), CIRBP (Affinity Capture-RNA), CIRBP (Affinity Capture-MS), CIRBP (Affinity Capture-MS), CIRBP (Reconstituted Complex), RBMX (Two-hybrid), CCNB2 (Co-fractionation), CIRBP (Co-fractionation)

ESM2 similar proteins: A0A0A0LLY1, A0A2R8Y4L2, A5A6H4, O89086, O93235, P04256, P09651, P09867, P10979, P17130, P21522, P27484, P49310, P49311, P49312, P51968, P51989, P51991, P51992, P60824, P60825, P60826, P98179, Q03250, Q03251, Q03878, Q05966, Q13151, Q14011, Q28521, Q28IQ9, Q2HJ60, Q32P51, Q38896, Q41188, Q43472, Q5RF83, Q61B10, Q6URK4, Q8BG05

Diamond homologs: A0A0A0LLY1, A0A0D1C8Z4, A5A6M3, C0HFE5, D3Z4I3, D4AE41, M0R7T6, O22703, O35698, O75526, O89086, O93235, P04147, P0C8Z4, P10979, P19682, P19683, P19684, P28644, P38159, P39697, P48809, P49310, P49311, P49313, P49314, P60824, P60825, P60826, P84586, P98179, Q03250, Q03251, Q03878, Q04836, Q05966, Q08473, Q08935, Q08937, Q14011

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 143 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
mRNA Polyadenylation	9	9.0×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of mRNA splicing, via spliceosome	5	22.8×	7e-04
intrinsic apoptotic signaling pathway	6	18.1×	3e-04
regulation of alternative mRNA splicing, via spliceosome	8	16.4×	3e-05
mRNA processing	11	7.3×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1899 predictions. Top by Δscore:

Variant	Effect	Δscore
19:1271033:GAAG:G	donor_gain	1.0000
19:1271037:GTG:G	donor_loss	1.0000
19:1271038:T:A	donor_loss	1.0000
19:1271133:T:TA	acceptor_gain	1.0000
19:1271136:A:AG	acceptor_gain	1.0000
19:1271136:ACAGT:A	acceptor_gain	1.0000
19:1271137:C:G	acceptor_gain	1.0000
19:1271137:CA:C	acceptor_loss	1.0000
19:1271138:A:AG	acceptor_gain	1.0000
19:1271138:AGT:A	acceptor_gain	1.0000
19:1271138:AGTG:A	acceptor_gain	1.0000
19:1271139:G:GT	acceptor_gain	1.0000
19:1271139:GT:G	acceptor_gain	1.0000
19:1271139:GTG:G	acceptor_gain	1.0000
19:1271139:GTGG:G	acceptor_gain	1.0000
19:1271139:GTGGT:G	acceptor_gain	1.0000
19:1271244:AAGG:A	donor_loss	1.0000
19:1271246:GGT:G	donor_loss	1.0000
19:1271248:T:A	donor_loss	1.0000
19:1271327:A:AG	acceptor_gain	1.0000
19:1271327:AGTCT:A	acceptor_gain	1.0000
19:1271328:G:GT	acceptor_gain	1.0000
19:1271328:GT:G	acceptor_gain	1.0000
19:1271328:GTC:G	acceptor_gain	1.0000
19:1271328:GTCT:G	acceptor_gain	1.0000
19:1271328:GTCTG:G	acceptor_gain	1.0000
19:1271976:TGCA:T	acceptor_loss	1.0000
19:1271977:GCA:G	acceptor_loss	1.0000
19:1271978:CA:C	acceptor_loss	1.0000
19:1271979:A:AC	acceptor_loss	1.0000

AlphaMissense

1896 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:1270956:T:A	L8H	1.000
19:1270956:T:C	L8P	1.000
19:1270958:T:C	F9L	1.000
19:1270959:T:C	F9S	1.000
19:1270959:T:G	F9C	1.000
19:1270960:T:A	F9L	1.000
19:1270960:T:G	F9L	1.000
19:1270962:T:A	V10D	1.000
19:1270965:G:A	G11E	1.000
19:1270971:T:A	L13Q	1.000
19:1270971:T:C	L13P	1.000
19:1270998:T:C	L22P	1.000
19:1271009:T:C	F26L	1.000
19:1271011:C:A	F26L	1.000
19:1271011:C:G	F26L	1.000
19:1271022:G:A	G30E	1.000
19:1271022:G:T	G30V	1.000
19:1271146:T:A	V37D	1.000
19:1271176:G:C	R47P	1.000
19:1271178:G:A	G48R	1.000
19:1271178:G:C	G48R	1.000
19:1271179:G:A	G48E	1.000
19:1271181:T:C	F49L	1.000
19:1271182:T:C	F49S	1.000
19:1271183:T:A	F49L	1.000
19:1271183:T:G	F49L	1.000
19:1271184:G:A	G50R	1.000
19:1271184:G:C	G50R	1.000
19:1271184:G:T	G50W	1.000
19:1271185:G:A	G50E	1.000

dbSNP variants (sampled 300 via entrez): RS1000552140 (19:1269140 G>A,T), RS1000665216 (19:1268990 C>T), RS1001184541 (19:1272547 C>T), RS1001218200 (19:1271878 C>T), RS1001274601 (19:1272644 G>A,C), RS1001336262 (19:1268903 G>T), RS1001490388 (19:1271825 T>G), RS1001626954 (19:1272790 G>C), RS1001649380 (19:1274980 A>C), RS1001765224 (19:1275107 T>C), RS1001986180 (19:1274273 G>A), RS1002151238 (19:1274458 G>A), RS1002529993 (19:1269319 G>A,C), RS1003169088 (19:1270237 C>A,G,T), RS1003283966 (19:1270358 G>A)

Disease associations

OMIM: gene MIM:602649 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002390_510	Mean corpuscular hemoglobin	2.000000e-19
GCST90002392_49	Mean corpuscular volume	4.000000e-19

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	5
methylmercuric chloride	decreases expression, increases expression	3
sodium arsenite	affects cotreatment, increases expression, decreases expression, increases abundance	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	2
Acetaminophen	increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Tretinoin	affects cotreatment, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression, affects cotreatment	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
beta-lapachone	increases expression	1
o,p’-DDT	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
ochratoxin A	decreases expression	1
vanadyl sulfate	decreases expression	1
beta-methylcholine	affects expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
pentabromodiphenyl ether	increases expression	1
K 7174	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2UE	Abcam HEK293T CIRBP KO	Transformed cell line	Female
CVCL_B8DS	Abcam HCT 116 CIRBP KO	Cancer cell line	Male
CVCL_B9G0	Abcam A-549 CIRBP KO	Cancer cell line	Male
CVCL_D2EF	Abcam MCF-7 CIRBP KO	Cancer cell line	Female

Clinical trials (associated diseases)

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