CCN5

Summary

CCN5 (cellular communication network factor 5, HGNC:12770) is a protein-coding gene on chromosome 20q13.12, encoding CCN family member 5 (O76076). May play an important role in modulating bone turnover.

This gene encodes a member of the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the connective tissue growth factor (CTGF) family. WNT1 is a member of a family of cysteine-rich, glycosylated signaling proteins that mediate diverse developmental processes. The CTGF family members are characterized by four conserved cysteine-rich domains: insulin-like growth factor-binding domain, von Willebrand factor type C module, thrombospondin domain and C-terminal cystine knot-like (CT) domain. The encoded protein lacks the CT domain which is implicated in dimerization and heparin binding. It is 72% identical to the mouse protein at the amino acid level. This gene may be downstream in the WNT1 signaling pathway that is relevant to malignant transformation. Its expression in colon tumors is reduced while the other two WISP members are overexpressed in colon tumors. It is expressed at high levels in bone tissue, and may play an important role in modulating bone turnover.

Source: NCBI Gene 8839 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 72 total
• MANE Select transcript: NM_003881

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12770
Approved symbol	CCN5
Name	cellular communication network factor 5
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	CT58, CTGF-L, WISP-2
Ensembl gene	ENSG00000064205
Ensembl biotype	protein_coding
OMIM	603399
Entrez	8839

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000190983, ENST00000372865, ENST00000372868, ENST00000465000, ENST00000471629, ENST00000497421, ENST00000885413, ENST00000885414

RefSeq mRNA: 3 — MANE Select: NM_003881 NM_001323369, NM_001323370, NM_003881

CCDS: CCDS13336, CCDS82619

Canonical transcript exons

ENST00000190983 — 4 exons

Exon	Start	End
ENSE00000556531	44719897	44720113
ENSE00001318709	44715369	44715450
ENSE00003536852	44724738	44724992
ENSE00003580023	44727087	44727811

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 99.50.

FANTOM5 (CAGE): breadth broad, TPM avg 13.2292 / max 1805.9910, expressed in 525 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184750	10.0718	440
184746	1.8979	379
184745	0.7820	246
184744	0.2174	103
184748	0.1684	77
184747	0.0573	24
184749	0.0344	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
popliteal artery	UBERON:0002250	99.50	gold quality
tibial artery	UBERON:0007610	99.50	gold quality
right coronary artery	UBERON:0001625	99.32	gold quality
aorta	UBERON:0000947	99.08	gold quality
left coronary artery	UBERON:0001626	98.88	gold quality
endocervix	UBERON:0000458	98.85	gold quality
thoracic aorta	UBERON:0001515	98.85	gold quality
ascending aorta	UBERON:0001496	98.83	gold quality
right lung	UBERON:0002167	98.42	gold quality
descending thoracic aorta	UBERON:0002345	98.27	gold quality
coronary artery	UBERON:0001621	98.07	gold quality
synovial joint	UBERON:0002217	97.95	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.81	gold quality
ectocervix	UBERON:0012249	97.80	gold quality
lower esophagus	UBERON:0013473	97.73	gold quality
right atrium auricular region	UBERON:0006631	97.56	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.51	gold quality
skin of leg	UBERON:0001511	97.44	gold quality
saphenous vein	UBERON:0007318	97.26	gold quality
right ovary	UBERON:0002118	97.20	gold quality
left ovary	UBERON:0002119	97.19	gold quality
tibial nerve	UBERON:0001323	96.80	gold quality
blood vessel layer	UBERON:0004797	96.52	gold quality
cardiac atrium	UBERON:0002081	96.02	gold quality
upper lobe of left lung	UBERON:0008952	95.82	gold quality
layer of synovial tissue	UBERON:0007616	95.54	gold quality
upper lobe of lung	UBERON:0008948	94.96	gold quality
zone of skin	UBERON:0000014	94.80	gold quality
adipose tissue	UBERON:0001013	94.73	gold quality
skin of abdomen	UBERON:0001416	94.68	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-126	yes	2836.02
E-MTAB-8322	yes	2109.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPD, CREB1, CTNNB1, CUX1, ELK1, ESR1, HTATIP2, NR3C1, TP53, TWIST1

miRNA regulators (miRDB)

27 targeting CCN5, 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-6867-5P	100.00	82.21	3464
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-7156-3P	98.25	67.66	859
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-3918	96.13	64.65	1300
HSA-MIR-8071	95.69	64.93	484
HSA-MIR-877-5P	94.62	66.30	710
HSA-MIR-5739	88.09	63.94	123

Literature-anchored findings (GeneRIF, showing 40)

• Overexpression of WISP2 is associated with breast cancer (PMID:11855747)
• disruption of WISP-2 signaling by use of antisense oligomers caused a significant reduction in breast tumor cell proliferation (PMID:12659671)
• WISP2 was overexpressed in gastrointestinal peptide-independent ACTH-independent macronodular adrenal hyperplasia. (PMID:14767469)
• regulation of phosphorylation of ER-alpha and EGFR may play critical roles in EGF-induced transcriptional activation of WISP-2 gene in breast tumor cells (PMID:15798095)
• These data demonstrate that the expression of WISP2 is synergistically upregulated in RA synovial fibroblasts by estrogen and WNT pathways, and suggest an involvement in the pathology of the disease. (PMID:16038875)
• Results suggest that WISP-2 could be a reliable independent marker and that down-regulation or loss of the WISP-2 gene may be associated with the development of salivary gland tumors. (PMID:16525711)
• WISP-2/CCN5 is a novel signaling molecule that critically participates in the mitogenic action of PMA on noninvasive, WISP-2/CCN5-positive breast tumor cells through PKCalpha-dependent, multiple molecular signal transduction pathways. (PMID:16939222)
• Data suggest WISP-2/CCN5 silencing may be a critical event during differentiation and progression of pancreatic adenocarcinoma. (PMID:17383817)
• WISP-2 had greater levels of expression in node-positive tumors; higher levels in both moderate and poor prognostic groups compared with the good prognostic group; greater level in both grade 2 and 3 when compared with grade 1. (PMID:17406949)
• WISP-2/CCN5 is an important regulator involved in the maintenance of a differentiated phenotype in breast tumor epithelial cells and may play a role in tumor cell invasion and metastasis (PMID:18070926)
• Loss of CCN5 is associated with gain of oncogenic function of p53 mutants invasiveness in breast cancer (PMID:18559502)
• CCN5 mRNA and protein level was almost undetectable in poorly differentiated breast cancers compared with the moderately or well-differentiated samples and its expression inversely correlated with lymph node positivity. (PMID:18794149)
• The CCN5/WISP2 were downregulated in paired comparisons of plexiform neurofibroma and malignant peripheral nerve sheath tumor. (PMID:20010302)
• WISPs may play important but contrasting roles in colorectal cancer with WISP-1 appearing to act as a factor stimulating aggressiveness, WISP-2 as a tumour suppressor and WISP-3 having no definable beneficial or detrimental role (PMID:20372786)
• CCN5 represses expression of genes associated with epithelial-mesenchymal transition (EMT) as well as expression of key components of the transforming growth factor beta (TGF-beta) signaling pathway. (PMID:21262769)
• Studies suggest a novel regulatory pathway exists through which CCN5 exerts its anti-invasive function. (PMID:22020939)
• WISP2 gene expression is regulated both by obesity and by the region between visceral and subcutaneous adipose tissue. (PMID:22616691)
• WISP2 regulates preadipocyte commitment and PPARgamma activation by BMP4. (PMID:23359679)
• overexpression of FGFBP1 or loss of WISP-2 expression is closely related to the metastasis, invasion and poor prognosis of gallbladder cancer. (PMID:23592278)
• Regulation of invasion by WISP2 may involve the WNT signalling pathway. (PMID:23893926)
• We demonstrate that the overexpression of CCN5 in lung fibroblasts suppresses the upregulation in the expression of alpha-SMA and collagen induced by CCN2. (PMID:24276150)
• WISP2 exerts dual actions in mesenchymal precursor cells; secreted WISP2 activates canonical WNT and maintains the cells in an undifferentiated state, whereas cytosolic WISP2 regulates adipogenic commitment. (PMID:24451367)
• Loss of WISP2 in estrogen-dependent MCF7 human breast cancer cells promotes a stem-like cell phenotype. (PMID:24498388)
• WISP2 has a role in regulating tumor cell susceptibility through EMT by inducing the TGF-beta signaling pathway, KLF-4 expression and miR-7 inhibition. (PMID:24931170)
• Serum WISP2 correlated directly with fatty acid binding protein 4. Serum SFRP5 did not differ between obese (n=32) vs. nonobese (n=25) PCOS women, but reference women had lower SFRP5 (p<5x10(-6) as compared to both PCOS groups). (PMID:25089371)
• Activation of CCN5 may have the therapeutic potential to kill triple-negative breast cancer. (PMID:25132260)
• The obtained results indicate that the changes in gene expression in bone marrow progenitor cells can be involved into space flight-induced osteopenia. (PMID:25509878)
• Report opposing effects of CCN2 and CCN5 on fibroblast proliferation and transdifferentiation induced by TGF-beta. (PMID:26218313)
• Studies indicate that the CYR61 CTGF NOV matricellular proteins (CCN family of proteins) comprises the members CCN1, CCN2, CCN3, CCN4, CCN5 and CCN6 and have been identified in various types of cancer. (PMID:26498181)
• CCN3 (Nov) and CCN5 (WISP2) are novel substrates of MMP14. (PMID:27471094)
• The authors show that, in triple-negative-breast cancer (TNBC) cells enriched with tumor initiating cells, CCN5 significantly blocks cellular growth via apoptosis, reversing epithelial-mesenchymal-transition-signaling and impairing mammosphere formation, thereby blocking the tumor-forming ability and invasive capacity of these cells. (PMID:28450698)
• Results show that WISP2 and beta-catenin were more highly expressed in gastric cancer tissues and seem to correlate with early stage or without metastasis. (PMID:28739741)
• by analyzing different estrogen receptor-alpha(ER-a)-positive and ER-a-negative breast cancer cell lines, we defined the role of CCN5 in the leptin-mediated regulation of growth and invasive capacity. (PMID:29370782)
• Our findings suggest that activation of WISP2 could be a useful therapeutic strategy for the treatment of esophageal squamous cell carcinoma (PMID:30808397)
• CCN5 inhibits proliferation and promotes apoptosis of oral squamous cell carcinoma cells. (PMID:31889370)
• WISP2 promotes cell proliferation via targeting ERK and YAP in ovarian cancer cells. (PMID:32711570)
• WISP2/IGF1 promotes the survival of DSCs and impairs the cytotoxicity of decidual NK cells. (PMID:33561006)
• Protective effect of estrogen receptors (ERalpha/beta) against the intervertebral disc degeneration involves activating CCN5 via the promoter. (PMID:33660790)
• Matricellular Protein WISP2 Is an Endogenous Inhibitor of Collagen Linearization and Cancer Metastasis. (PMID:34385183)
• Dual roles of WISP2 in the progression of hepatocellular carcinoma: implications of the fibroblast infiltration into the tumor microenvironment. (PMID:34497155)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccn5	ENSDARG00000077882
mus_musculus	Ccn5	ENSMUSG00000027656
rattus_norvegicus	Ccn5	ENSRNOG00000010666

Paralogs (5): CCN4 (ENSG00000104415), CCN6 (ENSG00000112761), CCN2 (ENSG00000118523), CCN3 (ENSG00000136999), CCN1 (ENSG00000142871)

Protein

Protein identifiers

CCN family member 5 — O76076 (reviewed: O76076)

Alternative names: Connective tissue growth factor-like protein, Connective tissue growth factor-related protein 58, WNT1-inducible-signaling pathway protein 2

All UniProt accessions (1): O76076

UniProt curated annotations — full annotation on UniProt →

Function. May play an important role in modulating bone turnover. Promotes the adhesion of osteoblast cells and inhibits the binding of fibrinogen to integrin receptors. In addition, inhibits osteocalcin production.

Subcellular location. Secreted.

Tissue specificity. Expressed in primary osteoblasts, fibroblasts, ovary, testes, and heart.

Similarity. Belongs to the CCN family.

Isoforms (2)

UniProt ID	Names	Canonical?
O76076-1	1	yes
O76076-2	2

RefSeq proteins (3): NP_001310298, NP_001310299, NP_003872* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00093, PF00219, PF19035

UniProt features (14 total): disulfide bond 6, domain 3, splice variant 2, signal peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O76076-F1	78.59	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (6): 70–100, 26–50, 30–52, 32–53, 39–56, 64–78

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 151 (showing top): MODULE_92, KOBAYASHI_EGFR_SIGNALING_24HR_UP, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, STOSSI_RESPONSE_TO_ESTRADIOL, GOBP_CELL_CELL_SIGNALING, SASAI_RESISTANCE_TO_NEOPLASTIC_TRANSFROMATION, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, AML_Q6, BOQUEST_STEM_CELL_CULTURED_VS_FRESH_DN, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, RIGGI_EWING_SARCOMA_PROGENITOR_DN

GO Biological Process (4): cell adhesion (GO:0007155), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), positive regulation of cell differentiation (GO:0045597)

GO Molecular Function (3): integrin binding (GO:0005178), heparin binding (GO:0008201), protein binding (GO:0005515)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), extracellular matrix (GO:0031012), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
cell communication	2
signaling	2
regulation of cellular process	1
cellular response to stimulus	1
cell differentiation	1
regulation of cell differentiation	1
positive regulation of cellular process	1
positive regulation of developmental process	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
binding	1
intracellular membrane-bounded organelle	1
external encapsulating structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

870 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCN5	WNT1	P04628	797
CCN5	VWF	P04275	626
CCN5	WNT4	P56705	600
CCN5	IGF1	P01343	565
CCN5	IGF2	P01344	484
CCN5	ZNF423	Q2M1K9	475
CCN5	CTNNB1	P35222	435
CCN5	NTRK1	P04629	431
CCN5	CADM4	Q8NFZ8	399
CCN5	SPARC	P09486	392
CCN5	CD99L2	Q8TCZ2	384
CCN5	CD99	P14209	382
CCN5	SFRP2	Q96HF1	380
CCN5	LY96	Q9Y6Y9	373
CCN5	ESR1	P03372	353

IntAct

11 interactions, top by confidence:

A	B	Type	Score
CCN5	HOXA1	psi-mi:“MI:0915”(physical association)	0.560
CCN5	ICAM1	psi-mi:“MI:0914”(association)	0.530
CCN5	TRIM68	psi-mi:“MI:0914”(association)	0.530
TFAP2A	CCN5	psi-mi:“MI:0915”(physical association)	0.370
CCN5	TFAP2C	psi-mi:“MI:0915”(physical association)	0.370
syd	CCN5	psi-mi:“MI:0915”(physical association)	0.000
fliH	CCN5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): PRKRIR (Affinity Capture-MS), CTU2 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), TRIM68 (Affinity Capture-MS), PITHD1 (Affinity Capture-MS), ICAM1 (Affinity Capture-MS), TRIM68 (Affinity Capture-MS), HOXA1 (Two-hybrid), TRIM68 (Affinity Capture-MS), ICAM1 (Affinity Capture-MS), UROS (Affinity Capture-MS), ERP44 (Affinity Capture-MS), WISP2 (Two-hybrid), WISP2 (Biochemical Activity), WISP2 (Biochemical Activity)

ESM2 similar proteins: A0JM12, A1A5Y0, A4FV93, A5PKD8, A6BM72, B2LW77, D3ZUK3, E9QJQ6, O00468, O75095, O76076, O88281, O95407, P15800, P23142, P31695, P55268, P97607, Q5VY43, Q5W7P8, Q61292, Q61982, Q6DIB5, Q6UXH1, Q6UY11, Q6ZWJ8, Q75N90, Q80T14, Q80T91, Q80V70, Q80W15, Q86XX4, Q8C088, Q8K1E3, Q8MJJ9, Q8N2S1, Q8VIK5, Q96I82, Q96KG7, Q99466

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, A2AJ76, A2ASQ1, A5PKD8, A5YT95, A9JRB3, D0NJ41, G4V4G1, O00468, O60575, O95633, O96790, P0CJ14, P0DKM9, P0DKT1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

653 predictions. Top by Δscore:

Variant	Effect	Δscore
20:44724869:G:GT	donor_gain	1.0000
20:44724908:A:T	donor_gain	1.0000
20:44724736:A:AG	acceptor_gain	0.9900
20:44724737:G:GG	acceptor_gain	0.9900
20:44724907:G:GT	donor_gain	0.9900
20:44720114:G:GG	donor_gain	0.9800
20:44724736:AGT:A	acceptor_gain	0.9800
20:44724737:GTG:G	acceptor_gain	0.9800
20:44724912:TCG:T	donor_gain	0.9800
20:44727082:CCTA:C	acceptor_loss	0.9800
20:44727084:TAGG:T	acceptor_loss	0.9800
20:44727085:A:T	acceptor_loss	0.9800
20:44727086:G:GA	acceptor_loss	0.9800
20:44722432:G:GT	donor_gain	0.9700
20:44724734:GCAGT:G	acceptor_loss	0.9700
20:44724735:CA:C	acceptor_loss	0.9700
20:44724737:G:GT	acceptor_loss	0.9700
20:44724737:GT:G	acceptor_gain	0.9700
20:44727085:A:AG	acceptor_gain	0.9700
20:44727086:G:GG	acceptor_gain	0.9700
20:44719896:GGTGC:G	acceptor_gain	0.9600
20:44724736:AGTG:A	acceptor_gain	0.9500
20:44724737:GTGG:G	acceptor_gain	0.9500
20:44724737:GTGGC:G	acceptor_gain	0.9500
20:44724886:C:G	donor_gain	0.9500
20:44724925:C:T	donor_gain	0.9500
20:44724940:G:GG	donor_gain	0.9500
20:44724939:A:AG	donor_gain	0.9400
20:44724990:AAGG:A	donor_loss	0.9400
20:44724992:GG:G	donor_loss	0.9400

AlphaMissense

1586 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:44724943:G:C	W161C	0.998
20:44724943:G:T	W161C	0.998
20:44724798:T:G	F113C	0.997
20:44727157:G:C	W201C	0.992
20:44727157:G:T	W201C	0.992
20:44724797:T:C	F113L	0.989
20:44724799:C:A	F113L	0.989
20:44724799:C:G	F113L	0.989
20:44724798:T:C	F113S	0.975
20:44724821:T:A	C121S	0.974
20:44724822:G:C	C121S	0.974
20:44724941:T:A	W161R	0.966
20:44724941:T:C	W161R	0.966
20:44720044:T:A	C70S	0.965
20:44720045:G:C	C70S	0.965
20:44724827:T:A	C123S	0.962
20:44724828:G:C	C123S	0.962
20:44724860:T:A	C134S	0.962
20:44724861:G:C	C134S	0.962
20:44724849:G:A	C130Y	0.956
20:44724848:T:A	C130S	0.954
20:44724849:G:C	C130S	0.954
20:44727221:T:A	C223S	0.951
20:44727222:G:C	C223S	0.951
20:44724758:T:A	C100S	0.950
20:44724759:G:C	C100S	0.950
20:44724929:T:A	C157S	0.949
20:44724930:G:C	C157S	0.949
20:44727145:G:C	W197C	0.949
20:44727145:G:T	W197C	0.949

dbSNP variants (sampled 300 via entrez): RS1000265194 (20:44727717 G>A), RS1000439480 (20:44715347 T>C,G), RS1000612489 (20:44722597 G>A), RS1000726204 (20:44716638 C>A), RS1000790689 (20:44715126 G>A,C), RS1000820627 (20:44717307 A>G), RS1000831937 (20:44717464 G>C), RS1001179814 (20:44716911 C>T), RS1001350842 (20:44727653 G>A), RS1001402298 (20:44721732 C>A,T), RS1001457884 (20:44721896 G>A), RS1001459782 (20:44722963 G>A), RS1001555159 (20:44721914 A>C), RS1001698580 (20:44727482 C>T), RS1001791758 (20:44723256 T>C)

Disease associations

OMIM: gene MIM:603399 | 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
GCST001762_470	Obesity-related traits	5.000000e-07
GCST006585_583	Blood protein levels	5.000000e-21

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004626	IGFBP-3 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects reaction, increases expression, affects expression, affects cotreatment, affects binding (+3 more)	14
bisphenol A	increases expression, affects binding, increases reaction, affects reaction, decreases reaction	5
Fulvestrant	decreases reaction, increases expression	4
Progesterone	affects cotreatment, decreases expression	3
sodium arsenite	decreases expression	2
Resveratrol	increases expression, decreases expression, affects cotreatment	2
Coumestrol	affects cotreatment, increases expression, decreases reaction	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
testosterone enanthate	affects cotreatment, decreases expression	1
propionaldehyde	increases expression	1
kaempferol	decreases reaction, increases expression	1
terbufos	increases methylation	1
arsenite	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
nickel chloride	increases expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
nonylphenol	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
4-nonylphenol	increases expression, decreases reaction	1
cetrorelix	affects cotreatment, decreases expression	1
glycidamide	decreases expression	1
27-hydroxycholesterol	increases expression, decreases reaction	1
1-bromopropane	increases expression, decreases reaction	1
2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane	increases expression, decreases reaction	1
bisphenol S	increases expression, decreases reaction	1

Clinical trials (associated diseases)

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