CRIP2

Summary

CRIP2 (cysteine rich protein 2, HGNC:2361) is a protein-coding gene on chromosome 14q32.33, encoding Cysteine-rich protein 2 (P52943).

This gene encodes a putative transcription factor with two LIM zinc-binding domains. The encoded protein may participate in the differentiation of smooth muscle tissue. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1397 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_001312

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2361
Approved symbol	CRIP2
Name	cysteine rich protein 2
Location	14q32.33
Locus type	gene with protein product
Status	Approved
Aliases	CRP2, ESP1
Ensembl gene	ENSG00000182809
Ensembl biotype	protein_coding
OMIM	601183
Entrez	1397

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 14 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000329146, ENST00000483017, ENST00000538259, ENST00000547643, ENST00000548309, ENST00000548923, ENST00000548989, ENST00000550577, ENST00000551738, ENST00000551836, ENST00000552643, ENST00000852172, ENST00000852173, ENST00000852174, ENST00000852175, ENST00000942976, ENST00000942977, ENST00000942978, ENST00000942979, ENST00000942980, ENST00000942981

RefSeq mRNA: 3 — MANE Select: NM_001312 NM_001270837, NM_001270841, NM_001312

CCDS: CCDS10003, CCDS59246

Canonical transcript exons

ENST00000329146 — 8 exons

Exon	Start	End
ENSE00001305445	105474821	105474905
ENSE00002338634	105479586	105480162
ENSE00003551850	105479436	105479493
ENSE00003567190	105478731	105478871
ENSE00003571158	105478266	105478360
ENSE00003626622	105479125	105479219
ENSE00003635215	105478450	105478507
ENSE00003650733	105478979	105479047

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 99.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.8614 / max 691.3117, expressed in 1527 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141910	32.9192	1497
141909	0.6983	293
141919	0.5811	346
141911	0.3241	163
141916	0.3149	177
141917	0.2570	125
207390	0.2444	118
141918	0.2172	114
141913	0.1538	84
141908	0.0559	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.78	gold quality
right atrium auricular region	UBERON:0006631	99.67	gold quality
right coronary artery	UBERON:0001625	99.56	gold quality
cardiac atrium	UBERON:0002081	99.55	gold quality
popliteal artery	UBERON:0002250	99.43	gold quality
tibial artery	UBERON:0007610	99.42	gold quality
ascending aorta	UBERON:0001496	99.40	gold quality
descending thoracic aorta	UBERON:0002345	99.40	gold quality
thoracic aorta	UBERON:0001515	99.39	gold quality
right uterine tube	UBERON:0001302	99.38	gold quality
left coronary artery	UBERON:0001626	99.38	gold quality
aorta	UBERON:0000947	99.36	gold quality
heart left ventricle	UBERON:0002084	99.32	gold quality
cardiac ventricle	UBERON:0002082	99.25	gold quality
coronary artery	UBERON:0001621	99.20	gold quality
adenohypophysis	UBERON:0002196	99.06	gold quality
lower esophagus	UBERON:0013473	98.96	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.96	gold quality
heart	UBERON:0000948	98.93	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.89	gold quality
right lung	UBERON:0002167	98.74	gold quality
tibial nerve	UBERON:0001323	98.69	gold quality
metanephros cortex	UBERON:0010533	98.62	gold quality
left uterine tube	UBERON:0001303	98.61	gold quality
anterior cingulate cortex	UBERON:0009835	98.60	gold quality
cortical plate	UBERON:0005343	98.59	gold quality
right lobe of thyroid gland	UBERON:0001119	98.56	gold quality
lower esophagus mucosa	UBERON:0035834	98.56	gold quality
cingulate cortex	UBERON:0003027	98.55	gold quality
mucosa of stomach	UBERON:0001199	98.50	gold quality

Single-cell (SCXA)

Detected in 28 experiment(s), a significant marker in 25.

Experiment	Marker?	Max mean expression
E-MTAB-8221	yes	1672.08
E-MTAB-9906	yes	1376.31
E-MTAB-8410	yes	1014.03
E-MTAB-7407	yes	455.76
E-MTAB-10855	yes	412.62
E-MTAB-8911	yes	263.37
E-MTAB-10287	yes	92.23
E-HCAD-1	yes	55.69
E-GEOD-134144	yes	51.39
E-HCAD-11	yes	50.80
E-GEOD-135922	yes	45.57
E-MTAB-8142	yes	43.76
E-HCAD-10	yes	41.83
E-CURD-46	yes	41.71
E-MTAB-6701	yes	38.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting CRIP2, 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-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-6767-5P	90.00	62.41	97
HSA-MIR-542-5P	87.47	60.42	76

Literature-anchored findings (GeneRIF, showing 8)

• Function of avian CRIP2 in smooth muscle differentiation (PMID:12530967)
• These findings suggest that ADAM19 autolysis is activated by lipopolysaccharide and that ADAM19 promotes the secretion of CRIP2. (PMID:20460109)
• CRIP2 acts as a transcription repressor of the NF-kappaB-mediated proangiogenic cytokine expression and thus functionally inhibits tumor formation and angiogenesis (PMID:21540330)
• CRIP2 expression is down-regulated in ESCC tissues and cell lines. (PMID:22154084)
• High CRP2 expression is associated with breast cancer cell invasion and metastasis. (PMID:26883198)
• HOXA9 inhibits HIF1A-mediated glycolysis through interacting with CRIP2 to repress cutaneous squamous cell carcinoma development. (PMID:29662084)
• APEX2-based Proximity Labeling of Atox1 Identifies CRIP2 as a Nuclear Copper-binding Protein that Regulates Autophagy Activation. (PMID:34550632)
• Prognosis biomarker and potential therapeutic target CRIP2 associated with radiosensitivity in NSCLC cells. (PMID:34773852)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	crip2l	ENSDARG00000033201
mus_musculus	Crip2	ENSMUSG00000006356
rattus_norvegicus	Crip2	ENSRNOG00000005041
rattus_norvegicus		ENSRNOG00000063576

Paralogs (20): FHL1 (ENSG00000022267), LMO3 (ENSG00000048540), LHX5 (ENSG00000089116), ZFHX4 (ENSG00000091656), LHX2 (ENSG00000106689), LHX6 (ENSG00000106852), LHX3 (ENSG00000107187), LHX4 (ENSG00000121454), LMO2 (ENSG00000135363), ZFHX2 (ENSG00000136367), LMX1B (ENSG00000136944), ZFHX3 (ENSG00000140836), LMO4 (ENSG00000143013), LHX9 (ENSG00000143355), CRIP3 (ENSG00000146215), LHX8 (ENSG00000162624), LMX1A (ENSG00000162761), LMO1 (ENSG00000166407), CRIP1 (ENSG00000213145), LHX1 (ENSG00000273706)

Protein

Protein identifiers

Cysteine-rich protein 2 — P52943 (reviewed: P52943)

Alternative names: Protein ESP1

All UniProt accessions (3): P52943, H0YFA4, H0YHD8

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with TGFB1I1.

Tissue specificity. Widespread tissue expression; highest levels in the heart.

Isoforms (2)

UniProt ID	Names	Canonical?
P52943-1	1	yes
P52943-2	2

RefSeq proteins (3): NP_001257766, NP_001257770, NP_001303* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain

Pfam: PF00412

UniProt features (19 total): strand 5, turn 4, modified residue 4, domain 2, chain 1, helix 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2CU8	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52943-F1	73.78	0.06

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): 23, 104, 138, 144

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 199 (showing top): MODULE_97, HORIUCHI_WTAP_TARGETS_DN, MYOGENIN_Q6, MODULE_169, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, MODULE_182, CAGCTG_AP4_Q5, EFC_Q6, UEDA_PERIFERAL_CLOCK, KESHELAVA_MULTIPLE_DRUG_RESISTANCE, GROSS_HYPOXIA_VIA_ELK3_UP, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_6

GO Biological Process (2): positive regulation of cell population proliferation (GO:0008284), hemopoiesis (GO:0030097)

GO Molecular Function (3): zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): cell cortex (GO:0005938)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell development	1
transition metal ion binding	1
binding	1
cation binding	1
cytoplasm	1
cell periphery	1

Protein interactions and networks

STRING

926 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRIP2	SRF	P11831	665
CRIP2	STEEP1	Q9H5V9	443
CRIP2	AGO2	Q9UKV8	433
CRIP2	CNR1	P21554	429
CRIP2	CLBA1	Q96F83	422
CRIP2	SLC25A6	P12236	406
CRIP2	MMUT	P22033	398
CRIP2	GLIPR2	Q9H4G4	386
CRIP2	DOK4	Q8TEW6	380
CRIP2	RPAIN	Q86UA6	379
CRIP2	NUDT14	O95848	374
CRIP2	NT5E	P21589	372
CRIP2	VWA5B2	Q8N398	349
CRIP2	NDRG4	Q9ULP0	336
CRIP2	LRWD1	Q9UFC0	334

IntAct

46 interactions, top by confidence:

A	B	Type	Score
SARNP	DDX39A	psi-mi:“MI:0914”(association)	0.740
SARNP	ZC3H11A	psi-mi:“MI:0914”(association)	0.610
ERBB2	CRIP2	psi-mi:“MI:0915”(physical association)	0.550
ERBB2	HAX1	psi-mi:“MI:0914”(association)	0.530
CRIP2	RELA	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
CRIP2	ATXN1	psi-mi:“MI:0915”(physical association)	0.370
CRIP2	ATP1B1	psi-mi:“MI:0915”(physical association)	0.370
GADD45G	CRIP2	psi-mi:“MI:0915”(physical association)	0.370
KLF10	CRIP2	psi-mi:“MI:0915”(physical association)	0.370
OSGEP	CRIP2	psi-mi:“MI:0915”(physical association)	0.370
CRIP2	PCYT2	psi-mi:“MI:0915”(physical association)	0.370
SMN1	CRIP2	psi-mi:“MI:0915”(physical association)	0.370
SPRY2	CRIP2	psi-mi:“MI:0915”(physical association)	0.370
CRIP2	TK1	psi-mi:“MI:0915”(physical association)	0.370
MYO1C	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
	VWA8	psi-mi:“MI:0914”(association)	0.350
BVLF1	VWA8	psi-mi:“MI:0914”(association)	0.350
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
ACOT6	ATP6V1G2	psi-mi:“MI:0914”(association)	0.350
AEN	CRIP2	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
SSX1	ACO1	psi-mi:“MI:0914”(association)	0.350
FMNL2	PLPBP	psi-mi:“MI:0914”(association)	0.350
MSC	TCF3	psi-mi:“MI:0914”(association)	0.350
VCP	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (57): CRIP2 (Reconstituted Complex), CRIP2 (Affinity Capture-MS), CRIP2 (Affinity Capture-MS), CRIP2 (Affinity Capture-MS), CRIP2 (Affinity Capture-MS), CRIP2 (Affinity Capture-MS), CRIP2 (Affinity Capture-MS), CRIP2 (Affinity Capture-MS), CRIP2 (Protein-RNA), CRIP2 (Two-hybrid), CRIP2 (Reconstituted Complex), CRIP2 (Affinity Capture-RNA), CRIP2 (Affinity Capture-MS), CRIP2 (Affinity Capture-MS), CRIP2 (Affinity Capture-MS)

ESM2 similar proteins: O00151, O04193, O35115, O70400, O70433, O80839, P21291, P29675, P36201, P47875, P50238, P50461, P50462, P50463, P50464, P52943, P52944, P53777, P63254, P63255, P67966, P67967, P97315, Q0VFX8, Q14192, Q16527, Q1ECF5, Q1LZA7, Q24400, Q2KI95, Q3MHY1, Q4KM31, Q4U0T9, Q500W4, Q56K04, Q5E9E1, Q5R7Y1, Q5RCT4, Q5RGJ5, Q5ZLR4

Diamond homologs: B0KYV5, D4A1F2, F1LR10, F1MF74, F1QH17, F1QWK4, F1RA39, F6QZ15, G3MWR8, G5EF51, O04193, O60952, O77506, O80839, O94851, P21291, P29675, P36201, P47875, P50460, P50461, P50462, P50463, P52943, P53777, P67966, P67967, P97314, P97315, Q05158, Q0E908, Q0VFX8, Q14847, Q16527, Q1ECF5, Q1LZA7, Q32LE9, Q3B7M5, Q3MHY1, Q4KM31

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKG1	unknown	CRIP2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 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
Cellular response to chemical stress	5	19.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1235 predictions. Top by Δscore:

Variant	Effect	Δscore
14:105474337:G:GT	donor_gain	1.0000
14:105478259:C:A	acceptor_gain	1.0000
14:105478264:A:AG	acceptor_gain	1.0000
14:105478265:G:GA	acceptor_gain	1.0000
14:105478265:GCC:G	acceptor_gain	1.0000
14:105478265:GCCGA:G	acceptor_gain	1.0000
14:105478448:A:AG	acceptor_gain	1.0000
14:105478449:G:GG	acceptor_gain	1.0000
14:105478727:GCAGG:G	acceptor_loss	1.0000
14:105478728:CAGGC:C	acceptor_loss	1.0000
14:105478837:G:GT	donor_gain	1.0000
14:105478869:GAG:G	donor_gain	1.0000
14:105478977:A:AG	acceptor_gain	1.0000
14:105478978:G:GC	acceptor_gain	1.0000
14:105479123:A:AG	acceptor_gain	1.0000
14:105479124:G:GG	acceptor_gain	1.0000
14:105479217:G:GT	donor_gain	1.0000
14:105479217:GAGG:G	donor_loss	1.0000
14:105479220:G:GA	donor_loss	1.0000
14:105479221:T:A	donor_loss	1.0000
14:105479226:G:T	donor_gain	1.0000
14:105479434:A:AG	acceptor_gain	1.0000
14:105479435:G:GG	acceptor_gain	1.0000
14:105474337:G:T	donor_gain	0.9900
14:105478264:AG:A	acceptor_loss	0.9900
14:105478265:GC:G	acceptor_gain	0.9900
14:105478358:GAGGT:G	donor_loss	0.9900
14:105478359:AGGTG:A	donor_loss	0.9900
14:105478360:GGTG:G	donor_loss	0.9900
14:105478361:G:T	donor_loss	0.9900

AlphaMissense

1349 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:105474875:T:C	C5R	1.000
14:105478295:T:A	W25R	1.000
14:105478295:T:C	W25R	1.000
14:105478297:G:C	W25C	1.000
14:105478297:G:T	W25C	1.000
14:105478307:T:C	C29R	1.000
14:105478316:T:A	C32S	1.000
14:105478316:T:C	C32R	1.000
14:105478317:G:C	C32S	1.000
14:105478468:T:C	C53R	1.000
14:105478480:T:C	C57R	1.000
14:105478499:G:A	G63E	1.000
14:105479017:T:C	C126R	1.000
14:105479154:T:A	W146R	1.000
14:105479154:T:C	W146R	1.000
14:105479156:G:C	W146C	1.000
14:105479156:G:T	W146C	1.000
14:105479166:T:C	C150R	1.000
14:105479170:T:C	L151P	1.000
14:105479175:T:A	C153S	1.000
14:105479175:T:C	C153R	1.000
14:105479176:G:C	C153S	1.000
14:105479184:T:A	C156S	1.000
14:105479184:T:C	C156R	1.000
14:105479185:G:A	C156Y	1.000
14:105479185:G:C	C156S	1.000
14:105479454:T:A	C174S	1.000
14:105479454:T:C	C174R	1.000
14:105479455:G:A	C174Y	1.000
14:105479455:G:C	C174S	1.000

dbSNP variants (sampled 300 via entrez): RS1001013417 (14:105474085 G>A,T), RS1002227634 (14:105473699 C>T), RS1002460344 (14:105479338 T>C), RS1002740023 (14:105478188 G>C,T), RS1003117198 (14:105478294 C>T), RS1003879487 (14:105475132 G>A,T), RS1005595030 (14:105473669 G>A), RS1005810491 (14:105478930 G>A,C,T), RS1005874753 (14:105472194 T>C), RS1005958548 (14:105473373 G>A,C,T), RS1006111617 (14:105478153 C>A,T), RS1006144310 (14:105478010 C>T), RS1006668523 (14:105473019 C>T), RS1006701395 (14:105472788 T>G), RS1006947011 (14:105478824 G>A)

Disease associations

OMIM: gene MIM:601183 | 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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects cotreatment, decreases methylation, decreases expression, increases expression	4
sodium arsenite	increases abundance, increases expression, affects expression, affects methylation, affects cotreatment (+1 more)	4
Tobacco Smoke Pollution	affects expression, decreases expression	3
Valproic Acid	increases expression, increases methylation, affects expression	3
Cyclosporine	decreases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Doxorubicin	affects expression	2
Smoke	decreases expression, increases abundance, increases expression	2
2,4,6-tribromophenol	decreases expression	1
propionaldehyde	increases expression	1
decabromobiphenyl ether	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
tetrahydropalmatine	decreases expression	1
arsenite	affects binding, decreases reaction	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
potassium chromate(VI)	decreases expression	1
monomethylarsonous acid	increases expression	1
nutlin 3	increases secretion, affects cotreatment, increases expression	1
ICG 001	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Bortezomib	decreases expression	1

Clinical trials (associated diseases)

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