CCN1

Summary

CCN1 (cellular communication network factor 1, HGNC:2654) is a protein-coding gene on chromosome 1p22.3, encoding CCN family member 1 (O00622). Promotes cell proliferation, chemotaxis, angiogenesis and cell adhesion.

The secreted protein encoded by this gene is growth factor-inducible and promotes the adhesion of endothelial cells. The encoded protein interacts with several integrins and with heparan sulfate proteoglycan. This protein also plays a role in cell proliferation, differentiation, angiogenesis, apoptosis, and extracellular matrix formation.

Source: NCBI Gene 3491 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_001554

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2654
Approved symbol	CCN1
Name	cellular communication network factor 1
Location	1p22.3
Locus type	gene with protein product
Status	Approved
Aliases	GIG1
Ensembl gene	ENSG00000142871
Ensembl biotype	protein_coding
OMIM	602369
Entrez	3491

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000451137, ENST00000480413, ENST00000674743, ENST00000674818, ENST00000675083, ENST00000676007, ENST00000866036, ENST00000920797, ENST00000920798, ENST00000968417

RefSeq mRNA: 1 — MANE Select: NM_001554 NM_001554

CCDS: CCDS706

Canonical transcript exons

ENST00000451137 — 5 exons

Exon	Start	End
ENSE00000956871	85581365	85581578
ENSE00000956872	85581928	85582284
ENSE00000956873	85582416	85582624
ENSE00001746075	85580761	85581047
ENSE00001770285	85582740	85583950

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 99.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.0538 / max 45.1243, expressed in 1007 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3828	336.1480	1532
201567	1.7838	842
3830	1.2700	710

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left uterine tube	UBERON:0001303	99.61	gold quality
smooth muscle tissue	UBERON:0001135	99.60	gold quality
gall bladder	UBERON:0002110	99.59	gold quality
vena cava	UBERON:0004087	99.58	gold quality
saphenous vein	UBERON:0007318	99.45	gold quality
blood vessel layer	UBERON:0004797	99.41	gold quality
mucosa of stomach	UBERON:0001199	99.40	gold quality
lower lobe of lung	UBERON:0008949	99.37	gold quality
omental fat pad	UBERON:0010414	99.32	gold quality
right coronary artery	UBERON:0001625	99.30	gold quality
peritoneum	UBERON:0002358	99.30	gold quality
left coronary artery	UBERON:0001626	99.24	gold quality
coronary artery	UBERON:0001621	99.18	gold quality
nipple	UBERON:0002030	99.14	gold quality
ascending aorta	UBERON:0001496	99.13	gold quality
tibia	UBERON:0000979	99.12	gold quality
thoracic aorta	UBERON:0001515	99.11	gold quality
mammary duct	UBERON:0001765	99.07	gold quality
parietal pleura	UBERON:0002400	99.07	gold quality
upper lobe of left lung	UBERON:0008952	99.03	gold quality
epithelium of mammary gland	UBERON:0003244	99.02	gold quality
aorta	UBERON:0000947	99.01	gold quality
trachea	UBERON:0003126	99.00	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.96	gold quality
upper lobe of lung	UBERON:0008948	98.95	gold quality
popliteal artery	UBERON:0002250	98.94	gold quality
tibial artery	UBERON:0007610	98.94	gold quality
ventricular zone	UBERON:0003053	98.88	gold quality
pleura	UBERON:0000977	98.86	gold quality
cardia of stomach	UBERON:0001162	98.80	gold quality

Single-cell (SCXA)

Detected in 29 experiment(s), a significant marker in 26.

Experiment	Marker?	Max mean expression
E-CURD-126	yes	5531.51
E-MTAB-6653	yes	4104.74
E-HCAD-23	yes	3366.25
E-MTAB-8410	yes	2993.37
E-MTAB-9906	yes	1423.17
E-GEOD-84465	yes	1418.74
E-CURD-7	yes	1381.28
E-ENAD-21	yes	1381.28
E-MTAB-8894	yes	968.82
E-HCAD-56	yes	924.29
E-GEOD-36552	yes	254.13
E-MTAB-6701	yes	129.71
E-HCAD-1	yes	75.46
E-MTAB-10287	yes	72.67
E-CURD-114	yes	61.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting CCN1, 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-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646

Literature-anchored findings (GeneRIF, showing 40)

• Elevated levels of connective tissue growth factor, WISP-1, and CYR61 in primary breast cancers associated with more advanced features. (PMID:11751417)
• Organization and expression of the Cyr61 gene in normal human fibroblasts. In serum-stimulated fibroblasts, an alternative RNA containing an in-frame deletion within exon 4 which disrupts the thrombospondin type 1 repeat was detected. (PMID:11810026)
• promotes tumor growth; increased Cyr61 expression is associated with an aggressive phenotype of breast cancer cells (PMID:11840342)
• Identification of integrin alpha(M)beta(2) as an adhesion receptor on human peripheral blood monocytes for Cyr61 and connective tissue growth factor: immediate-early gene products expressed in atherosclerotic lesions. (PMID:12036876)
• Cyr61 is an early marker of extracellular matrix remodeling in rat bladder cells (PMID:12217894)
• role in promoting cell survival and tubule formation in human umbilical vein endothelial cells (PMID:12364323)
• in addition to its proangiogenic activity, Cyr61 may be a novel mediator of progesterone activity in enhancing growth-factor-driven tumor growth in breast cancer. (PMID:12374462)
• Cyr61 promotes breast tumorigenesis and cancer progression (PMID:12444554)
• CYR61 has an integrin alphaMbeta2 binding site mediating monocyte adhesion (PMID:12736251)
• these findings define the T1 sequence in CCN1 as a novel binding motif for integrin alpha 6 beta 1 (PMID:12826661)
• Regulates angiogenesis and endothelial cell function. (review) (PMID:12831056)
• The expression of the CYR61 gene depends on the physiologic state of G-actin monomers (PMID:12899698)
• Cyr61 is a hypoxia-inducible angiogenesis factor in malignant melanoma with tumor stage-dependent expression (PMID:12939282)
• Lysophosphatidic acids induce CYR61 by activating G protein-coupled receptors. CYR61 acts as secreted autocrine and/or paracrine mediator in stromal and epithelial hyperplasia. Potential importance of this signaling mechanism in the disease. (PMID:14988385)
• CYR61 and CTGF may play a role in the progression of gliomas; their levels at diagnosis may have prognostic significance. (PMID:15041728)
• Cyr61 plays an important role in resistance to chemotherapeutic agent-induced apoptosis in human breast cancer MCF-7 cells by a mechanism involving the activation of the integrins/NF-kappaB/XIAP signaling pathway (PMID:15044484)
• Results suggest that Cyr61 may represent a gene characteristic for endometriosis and may play an important role in the development and persistence of endometriotic lesions. (PMID:15044605)
• evidence that adenylate cyclase as well as one or several protein kinases might be involved in the mechanoregulation of Cyr61, CTGF and Nov genes (PMID:15053922)
• serum growth factors induce the cysteine rich angiogenic inducer 61(CYR61) gene in both prostate stromal and epithelial cells, and CYR61 plays functional roles in cell adhesion, morphology, and proliferation (PMID:15389821)
• Cyr61 has a role in suppressing growth of human endometrial cancer cells (PMID:15471875)
• Cyr61 and CTGF genes may play an important role in hepatocellular carcinogenesis and correlate with recurrence and metastasis of hepatocellular carcinoma (PMID:15526358)
• new role for cyr61 in HeLa cells infected with Coxsackievirus B3, which is associated with the cell death induced by virus infection (PMID:15564459)
• CYR61 is sufficient to promote breast cancer cell proliferation, cell survival, and Taxol resistance. (PMID:15592521)
• Cyr61 gene expression is significantly downregulated in the tumors of hepatocellular carcinoma patients. (PMID:15782120)
• Recombinant cyr61 was expressed as a fusion protein with the Fc-domain of human IgG and purified using affinity chromatography on protein G-Sepharose columns. rCyr61 stimulated blood vessel formation and cell proliferation. (PMID:15878827)
• Cyr61 expression provides cytoprotection in hyperoxia-induced pulmonary epithelial cell death and that this effect was in part mediated via the Akt signaling pathway (PMID:15961723)
• Results suggest that CCN1 may play a role in ovarian carcinogenesis by stimulating survival and antiapoptotic signaling pathways. (PMID:16243794)
• CYR61 is regulated by the Wnt signal and plays an important role in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells. (PMID:16581771)
• In early-onset pre-eclamptic placentae, CYR61 was expressed at a significantly lower level compared with normal matched controls, indicating a potential role of this molecule in the pathogenesis of early-onset pre-eclampsia. (PMID:16675545)
• The 3 most significantly overexpressed genes in rheumatoid arthritis were laeverin, 11beta-hydroxysteroid dehydrogenase type 2 (a steroid pathway enzyme), and cysteine-rich, angiogenic inducer 61 (a known angiogenic factor). (PMID:16804865)
• These data identify CYR61 as a pivotal regulator of collagen production and degradation in aged and photoaged human skin. (PMID:16877350)
• IGFBP-3, IGFBP-4, and IGFBP-10/CYR61 mRNA levels were up-regulated in Barrett’s and tumour tissue of oesophageal adenocarcinoma patients (PMID:17056474)
• Experiments using a recombinant mutant human CYR61 promoter-directed reporter gene expression confirmed transcriptional regulation of CYR61 by FOXO3a. (PMID:17234971)
• CCN1 promotes integrin-dependent recruitment of CD34+ progenitor cells to endothelial cells, which may contribute to paracrine effects on angiogenesis and tissue regeneration. (PMID:17429007)
• We found significant differences in gene expression, specifically with a group of genes, including CYR61, known to be responsive to estrogen or to interact with estrogen receptor. (PMID:17437852)
• Downregulation of the Cyr61 is associated with lung cancer. (PMID:17579708)
• In normal endometrium Cyr61 expression is highest in proliferatory phase; it is overexpressed in midsecretory phase in polycystic ovary syndrome (PCOS) and endometrial cancer. (PMID:17601910)
• VEGF-mediated up-regulation of CCN1 in osteoblasts that attracts endothelial cells and promotes angiogenesis. Such a loop could be operative during fracture healing. (PMID:17626014)
• Exercise with high mechanical loading induced the expression of Cyr61 in human skeletal muscle. (PMID:17673559)
• CCN1 is expressed in podocytes, acts on glomerular cells to modulate glomerular remodeling, and is downregulated in diseased kidneys. Impairment of CCN1 expression in podocytes may contribute to progression of glomerular disease with mesangial expansion. (PMID:17699553)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccn1	ENSDARG00000023062
mus_musculus	Ccn1	ENSMUSG00000028195
rattus_norvegicus	Ccn1	ENSRNOG00000014350

Paralogs (5): CCN5 (ENSG00000064205), CCN4 (ENSG00000104415), CCN6 (ENSG00000112761), CCN2 (ENSG00000118523), CCN3 (ENSG00000136999)

Protein

Protein identifiers

CCN family member 1 — O00622 (reviewed: O00622)

Alternative names: Cellular communication network factor 1, Cysteine-rich angiogenic inducer 61, Insulin-like growth factor-binding protein 10, Protein CYR61, Protein GIG1

All UniProt accessions (3): O00622, A0A6Q8PGQ1, Q6FI18

UniProt curated annotations — full annotation on UniProt →

Function. Promotes cell proliferation, chemotaxis, angiogenesis and cell adhesion. Appears to play a role in wound healing by up-regulating, in skin fibroblasts, the expression of a number of genes involved in angiogenesis, inflammation and matrix remodeling including VEGA-A, VEGA-C, MMP1, MMP3, TIMP1, uPA, PAI-1 and integrins alpha-3 and alpha-5. CCN1-mediated gene regulation is dependent on heparin-binding. Down-regulates the expression of alpha-1 and alpha-2 subunits of collagen type-1. Promotes cell adhesion and adhesive signaling through integrin alpha-6/beta-1, cell migration through integrin alpha-v/beta-5 and cell proliferation through integrin alpha-v/beta-3.

Subunit / interactions. Interaction with integrins is heparin- and cell-type-dependent and promotes cell adhesion. In skin fibroblasts it binds ITGA6/ITGB1, in endothelial cells, binds ITGAV/ITGB3 and in platelets, ITGA2B/ITGB3. Binds, in vitro, ITGAV/ITGB5.

Subcellular location. Secreted.

Similarity. Belongs to the CCN family.

RefSeq proteins (1): NP_001545* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000867	IGFBP-like	Domain
IPR000884	TSP1_rpt	Repeat
IPR001007	VWF_dom	Domain
IPR006207	Cys_knot_C	Domain
IPR006208	Glyco_hormone_CN	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR012395	IGFBP_CNN	Family
IPR017891	Insulin_GF-bd_Cys-rich_CS	Conserved_site
IPR036383	TSP1_rpt_sf	Homologous_superfamily
IPR043973	TSP1_CCN	Domain
IPR050941	CCN	Family

Pfam: PF00007, PF00093, PF00219, PF19035

UniProt features (24 total): disulfide bond 11, domain 4, sequence conflict 4, signal peptide 1, chain 1, sequence variant 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4D0Z	X-RAY DIFFRACTION	2.2
4D11	X-RAY DIFFRACTION	2.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00622-F1	72.85	0.22

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): 188

Disulfide bonds (11): 32–53, 39–56, 64–78, 70–91, 286–323, 303–337, 314–353, 317–355, 322–359, 26–50, 30–52

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 553 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, MODULE_52, TSUNODA_CISPLATIN_RESISTANCE_UP, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, HNF3ALPHA_Q6, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_REGULATION_OF_CARTILAGE_DEVELOPMENT

GO Biological Process (35): osteoblast differentiation (GO:0001649), intussusceptive angiogenesis (GO:0002041), atrioventricular valve morphogenesis (GO:0003181), apoptotic process involved in heart morphogenesis (GO:0003278), ventricular septum development (GO:0003281), chemotaxis (GO:0006935), cell adhesion (GO:0007155), signal transduction (GO:0007165), integrin-mediated signaling pathway (GO:0007229), positive regulation of cell-substrate adhesion (GO:0010811), extracellular matrix organization (GO:0030198), positive regulation of cell migration (GO:0030335), positive regulation of bone mineralization (GO:0030501), positive regulation of BMP signaling pathway (GO:0030513), positive regulation of osteoblast proliferation (GO:0033690), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), positive regulation of cell differentiation (GO:0045597), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of transcription by RNA polymerase II (GO:0045944), atrial septum morphogenesis (GO:0060413), chondroblast differentiation (GO:0060591), chorio-allantoic fusion (GO:0060710), labyrinthine layer blood vessel development (GO:0060716), positive regulation of cartilage development (GO:0061036), regulation of ERK1 and ERK2 cascade (GO:0070372), reactive oxygen species metabolic process (GO:0072593), positive regulation of ceramide biosynthetic process (GO:2000304), apoptotic process (GO:0006915), positive regulation of biosynthetic process (GO:0009891), regulation of macromolecule biosynthetic process (GO:0010556), positive regulation of ossification (GO:0045778), positive regulation of developmental process (GO:0051094), cell-cell adhesion (GO:0098609), regulation of multicellular organismal development (GO:2000026)

GO Molecular Function (6): integrin binding (GO:0005178), heparin binding (GO:0008201), growth factor binding (GO:0019838), extracellular matrix binding (GO:0050840), extracellular matrix structural constituent (GO:0005201), protein binding (GO:0005515)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), extracellular matrix (GO:0031012), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of proteins	2
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	2
cellular process	2
apoptotic process	2
regulation of apoptotic process	2
binding	2
ossification	1
angiogenesis	1
atrioventricular valve development	1
heart valve morphogenesis	1
heart morphogenesis	1
apoptotic process involved in morphogenesis	1
cardiac ventricle development	1
cardiac septum development	1
response to chemical	1
taxis	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor signaling pathway	1
regulation of cell-substrate adhesion	1
cell-substrate adhesion	1
positive regulation of cell adhesion	1
extracellular structure organization	1
external encapsulating structure organization	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
bone mineralization	1
regulation of bone mineralization	1
positive regulation of ossification	1
positive regulation of biomineral tissue development	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of cell population proliferation	1
osteoblast proliferation	1
regulation of osteoblast proliferation	1
positive regulation of programmed cell death	1
negative regulation of programmed cell death	1

Protein interactions and networks

STRING

1952 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCN1	IGFBP7	Q16270	919
CCN1	ITGAV	P06756	788
CCN1	VWF	P04275	784
CCN1	SPARC	P09486	764
CCN1	LATS1	O95835	753
CCN1	ANKRD1	Q15327	750
CCN1	YAP1	P46937	681
CCN1	AZU1	P20160	678
CCN1	TEAD1	P28347	677
CCN1	EGR1	P18146	675
CCN1	ITGB3	P05106	663
CCN1	CD44	P16070	662
CCN1	FOS	P01100	655
CCN1	AMOTL2	Q9Y2J4	652
CCN1	THBS1	P07996	650

IntAct

42 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CCN1	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
CCN1	SMPD2	psi-mi:“MI:0915”(physical association)	0.560
APOD	CCN1	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
ZWINT		psi-mi:“MI:0915”(physical association)	0.400
Mis12	CCN1	psi-mi:“MI:0915”(physical association)	0.400
CNTROB	CENPX	psi-mi:“MI:0914”(association)	0.350
MYC	ILVBL	psi-mi:“MI:0914”(association)	0.350
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
SOX2	DDX39A	psi-mi:“MI:0914”(association)	0.350
CFTR	POTEF	psi-mi:“MI:0914”(association)	0.350
	CCN1	psi-mi:“MI:0914”(association)	0.350
CASP8	CCN1	psi-mi:“MI:0914”(association)	0.350
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350
ADAMTS1	CCN1	psi-mi:“MI:0914”(association)	0.350
ATF3	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (53): CYR61 (Affinity Capture-MS), CYR61 (Affinity Capture-MS), CYR61 (Affinity Capture-MS), CYR61 (Affinity Capture-MS), CYR61 (Affinity Capture-MS), CYR61 (Affinity Capture-MS), CYR61 (Affinity Capture-MS), CYR61 (Two-hybrid), UBQLN2 (Two-hybrid), CYR61 (Affinity Capture-MS), CYR61 (Affinity Capture-RNA), CYR61 (Reconstituted Complex), CYR61 (Affinity Capture-MS), CYR61 (Proximity Label-MS), CYR61 (Reconstituted Complex)

ESM2 similar proteins: A0A0R4IKU3, A0A8M9PFP2, A1A5Y0, A2A863, A2VCU8, A5A6L1, B0S5G3, L7VG99, O00622, O08841, O35118, O42493, O93512, P08163, P08833, P16042, P16144, P17668, P18406, Q07663, Q0VCN6, Q13753, Q501P1, Q53RD9, Q5R9Q9, Q61220, Q61592, Q64632, Q6DDW2, Q7T3Q2, Q7ZV46, Q7ZXL5, Q8R4Y4, Q8R553, Q8VDA1, Q91166, Q91167, Q91713, Q99JH7, Q9BQT9

Diamond homologs: A5A6L1, D3Z5L9, D3ZKF5, O00622, O18739, O19113, O54775, O76076, O95388, O95389, P18406, P19336, P28686, P29268, P29279, P42642, P48745, P51609, Q64299, Q99PP0, Q9ES72, Q9JHC6, Q9QZQ5, Q9R1E9, Q9Z0G4, E1BJW1, Q98UI9, Q9NQ30, A2RT60, A4IIA2, A9JRB3, P12843, P47877, Q5XHC5, Q9JLL0, Q9NZV1, Q80T14, P97682, Q9QYY7, Q7T3Q2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	3
Benign	15

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2498 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:85581509:T:A	C70S	1.000
1:85581510:G:A	C70Y	1.000
1:85581510:G:C	C70S	1.000
1:85581533:T:A	C78S	1.000
1:85581534:G:C	C78S	1.000
1:85581572:T:A	C91S	1.000
1:85581573:G:A	C91Y	1.000
1:85581573:G:C	C91S	1.000
1:85581574:C:G	C91W	1.000
1:85581939:G:T	G97C	1.000
1:85581948:T:A	C100S	1.000
1:85581948:T:C	C100R	1.000
1:85581949:G:A	C100Y	1.000
1:85581949:G:C	C100S	1.000
1:85581949:G:T	C100F	1.000
1:85581950:T:G	C100W	1.000
1:85581987:T:C	F113L	1.000
1:85581988:T:C	F113S	1.000
1:85581988:T:G	F113C	1.000
1:85581989:C:A	F113L	1.000
1:85581989:C:G	F113L	1.000
1:85582011:T:A	C121S	1.000
1:85582011:T:C	C121R	1.000
1:85582012:G:C	C121S	1.000
1:85582013:C:G	C121W	1.000
1:85582017:T:A	C123S	1.000
1:85582017:T:C	C123R	1.000
1:85582018:G:A	C123Y	1.000
1:85582018:G:C	C123S	1.000
1:85582019:T:G	C123W	1.000

dbSNP variants (sampled 300 via entrez): RS1000706725 (1:85579245 G>C), RS1000846287 (1:85580855 C>G,T), RS1001078275 (1:85579665 G>A,C,T), RS1002071007 (1:85580184 G>C), RS1002730214 (1:85582258 A>T), RS1002786926 (1:85580743 G>C), RS1003234344 (1:85582639 G>A), RS1004079244 (1:85583196 G>A), RS1004412930 (1:85583631 A>G), RS1004844369 (1:85578838 C>T), RS1005696455 (1:85581813 A>C,G,T), RS1006868273 (1:85581318 T>A), RS1006873852 (1:85578858 G>A,C), RS1006894670 (1:85581558 C>G,T), RS1007209365 (1:85581217 T>G)

Disease associations

OMIM: gene MIM:602369 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST007269_24	Pulse pressure	7.000000e-09
GCST009391_1535	Metabolite levels	1.000000e-09
GCST012033_1	Sleep (1/3-day periodicity)	4.000000e-08
GCST90020024_15	A body shape index	3.000000e-09
GCST90020029_1257	Waist circumference adjusted for body mass index	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0010510	NG-monomethyl-arginine measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression	8
Valproic Acid	affects cotreatment, increases expression, affects expression	7
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	6
Estradiol	decreases expression, affects expression, affects cotreatment, increases expression	5
Aflatoxin B1	affects expression, increases expression	5
sodium arsenite	decreases reaction, affects methylation, affects binding, increases expression, increases methylation (+3 more)	4
Cyclosporine	increases expression, affects expression, decreases expression	4
bisphenol A	affects cotreatment, decreases methylation, decreases expression	3
Copper	increases expression, affects binding	3
Fluorouracil	affects response to substance, increases expression	3
Hydrogen Peroxide	increases expression, affects expression	3
Lipopolysaccharides	affects response to substance, affects reaction, affects expression, increases expression	3
methylparaben	decreases expression, increases expression	2
cupric chloride	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
torcetrapib	increases expression	2
Capecitabine	decreases expression, decreases response to substance	2
Troglitazone	decreases expression	2
Acetaminophen	increases expression	2
Ethanol	decreases reaction, increases expression, increases reaction, decreases expression	2
Carbamazepine	affects expression	2
Diclofenac	affects expression, increases expression	2
Formaldehyde	increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Silicon Dioxide	increases expression	2
Silver	increases expression	2
Tobacco Smoke Pollution	affects expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression, decreases expression	2

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1PR	Abcam HeLa CCN1 KO	Cancer cell line	Female
CVCL_SK28	HAP1 CYR61 (-) 1	Cancer cell line	Male
CVCL_XN07	HAP1 CYR61 (-) 2	Cancer cell line	Male
CVCL_XN08	HAP1 CYR61 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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