CAV2

Summary

CAV2 (caveolin 2, HGNC:1528) is a protein-coding gene on chromosome 7q31.2, encoding Caveolin-2 (P51636). May act as a scaffolding protein within caveolar membranes.

The protein encoded by this gene is a major component of the inner surface of caveolae, small invaginations of the plasma membrane, and is involved in essential cellular functions, including signal transduction, lipid metabolism, cellular growth control and apoptosis. This protein may function as a tumor suppressor. This gene and related family member (CAV1) are located next to each other on chromosome 7, and express colocalizing proteins that form a stable hetero-oligomeric complex. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. Additional isoforms resulting from the use of alternate in-frame translation initiation codons have also been described, and shown to have preferential localization in the cell (PMID:11238462).

Source: NCBI Gene 858 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis (Limited, ClinGen)
• GWAS associations: 44
• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_001233

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1528
Approved symbol	CAV2
Name	caveolin 2
Location	7q31.2
Locus type	gene with protein product
Status	Approved
Aliases	CAV
Ensembl gene	ENSG00000105971
Ensembl biotype	protein_coding
OMIM	601048
Entrez	858

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding_CDS_not_defined, 4 protein_coding

ENST00000222693, ENST00000343213, ENST00000393480, ENST00000460222, ENST00000462876, ENST00000465451, ENST00000467035, ENST00000472470, ENST00000477018, ENST00000478226, ENST00000484871, ENST00000485561, ENST00000490906, ENST00000495841, ENST00000498493, ENST00000892151

RefSeq mRNA: 4 — MANE Select: NM_001233 NM_001206747, NM_001206748, NM_001233, NM_198212

CCDS: CCDS5765, CCDS5766

Canonical transcript exons

ENST00000222693 — 3 exons

Exon	Start	End
ENSE00000881890	116499738	116499931
ENSE00001864005	116505971	116508541
ENSE00003480563	116500260	116500447

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 60.8482 / max 1036.7160, expressed in 1534 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80614	41.6422	1485
80613	14.8427	1401
80615	1.8790	799
80617	1.0019	469
80611	0.7762	418
80616	0.3040	158
80618	0.2173	102
80610	0.1009	49
80612	0.0839	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	99.35	gold quality
heart right ventricle	UBERON:0002080	98.93	gold quality
blood vessel layer	UBERON:0004797	98.88	gold quality
vena cava	UBERON:0004087	98.86	gold quality
myocardium	UBERON:0002349	98.53	gold quality
urethra	UBERON:0000057	98.40	gold quality
synovial joint	UBERON:0002217	98.31	gold quality
parietal pleura	UBERON:0002400	98.30	gold quality
adipose tissue	UBERON:0001013	98.24	gold quality
skin of hip	UBERON:0001554	98.24	gold quality
right coronary artery	UBERON:0001625	98.16	gold quality
cardiac atrium	UBERON:0002081	98.10	gold quality
right atrium auricular region	UBERON:0006631	98.07	gold quality
right lung	UBERON:0002167	98.04	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.03	gold quality
left ventricle myocardium	UBERON:0006566	97.98	gold quality
pericardium	UBERON:0002407	97.97	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.97	gold quality
cardiac ventricle	UBERON:0002082	97.96	gold quality
pleura	UBERON:0000977	97.95	gold quality
saphenous vein	UBERON:0007318	97.94	gold quality
heart left ventricle	UBERON:0002084	97.93	gold quality
heart	UBERON:0000948	97.84	gold quality
palpebral conjunctiva	UBERON:0001812	97.84	gold quality
connective tissue	UBERON:0002384	97.83	gold quality
left lobe of thyroid gland	UBERON:0001120	97.80	gold quality
germinal epithelium of ovary	UBERON:0001304	97.78	gold quality
left coronary artery	UBERON:0001626	97.76	gold quality
lung	UBERON:0002048	97.74	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.67	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	129.25
E-MTAB-7008	yes	101.98
E-MTAB-10287	yes	45.78
E-HCAD-1	yes	39.93
E-MTAB-8410	yes	28.64
E-MTAB-5061	yes	27.82
E-MTAB-10553	yes	23.14
E-HCAD-11	yes	21.96
E-MTAB-6701	yes	15.71
E-CURD-46	yes	13.35
E-GEOD-130148	yes	13.06
E-GEOD-135922	yes	10.27
E-HCAD-13	yes	8.23
E-GEOD-134144	yes	8.04
E-ENAD-27	yes	6.56

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

157 targeting CAV2, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3658	99.96	73.87	4379

Literature-anchored findings (GeneRIF, showing 40)

• Data show that ER alpha and not ER beta silences caveolin-1/-2 expression in an epigenetic fashion in neuronal cells. (PMID:12138116)
• In Caco-2 cells, a polarized cell line derived from human colon cancer that does not express caveolin 1 (Cav-1), there was no detectable expression of caveolin 2 (Cav-2). (PMID:12414992)
• caveolin-2 may play a role in lamellar granule assembly, trafficking, and/or function. (PMID:12648214)
• PPARgamma ligands increased the levels of caveolin-2 2-5-fold in a concentration-dependent manner within 24 h. Nonthiazolidinedione PPARgamma ligands elevated caveolin-2 protein 3-4-fold. (PMID:12813462)
• New evidence demonstrating that Cav-2 undergoes phosphorylation at both tyrosines 19 and 27 also reveals that tyrosine phosphorylation of Cav-2 has no effect on its targeting to lipid rafts, but clearly disrupts hetero-oligomerization of Cav-2 with Cav-1. (PMID:15504032)
• Heterologously and endogenously expressed D1 dopamine receptors in renal cells are associated with and regulated by caveolin-2. (PMID:15569306)
• Actin cytoskeleton is involved as part of a caveolar complex in the regulation of myometrial maxi-K channel function. (PMID:15703204)
• increased expression of caveolins in proliferating bile ductules in primary biliary cirrhosis may be related to the homeostasis of cholesterol transport in regenerating bile ductules in liver (PMID:15968725)
• Overexpression of caveolin-2 is associated with inflammatory breast cancer (PMID:16244790)
• CAV2 identified and immunolocalized in the caveola-vesicle complexes (CVC )present in erythrocytes infected with P. vivax (PMID:16521037)
• caveolae and caveolins are integral membrane components in basal and ciliated epithelial cellsin rats, mice, and humans, indicating a crucial role in these cell types; in addition to their physiological role, they may be involved in airway infection (PMID:16904002)
• The presence of different caveolin isoforms in many cell types of the human retina, is reported. (PMID:17615539)
• Positive staining resulted in shorter survival in patients with esophageal squamous cell carcinoma. (PMID:17671707)
• Caveolin-2 was expressed in the sinusoidal endothelial cells and the smooth muscle cells of the unparied arteries of hepatpcellular carcinoma specimens. (PMID:17898556)
• CAV2 is preferentially expressed in basal-like cancers and is associated with poor prognosis (PMID:17912630)
• Data suggests a possible involvement of serine 36-phosphorylated caveolin-2 in modulating mitosis. (PMID:18081315)
• Single Nucleotide Polymorphisms in CAV2 is associated with primary open-angle glaucoma. (PMID:20835238)
• We found preliminary evidence that CAV2 rs2270188 interacts with dietary fat to affect risk of type 2 diabetes. (PMID:21178094)
• data and observations imply that a primary open angle glaucoma (POAG) risk allele at the 7q31 locus that contains the caveolin genes CAV1 and CAV2 is not strongly associated with glaucoma in an Iowa population (PMID:21321670)
• cav-2 acts as a modulator of cancer progression. (PMID:21373752)
• The combination of the expression of the genes for PPARgamma, STMN1 and CAV2 was significantly predictive for early recurrence of non-muscle-invasive bladder cancer (PMID:21489836)
• CAV1 mRNA and protein levels are reduced by both NFBD1 knockdown and knockout independently of IR and p53 (PMID:21551225)
• The identified single nucleotide polymorphisms are associated with primary open-angle glaucoma in the Caucasian US population and that specific haplotypes located in the CAV1/CAV2 intergenic region are associated with the disease. (PMID:21873608)
• Stromal caveolin-2 expression were more frequent in anaplastic carcinoma and diffuse sclerosing variant of papillary carcinoma compared to conventional papillary thyroid carcinoma. (PMID:22236542)
• In contrast to wild-type-Cav-2, retroviral re-expression of Y19/27F-Cav-2 in Cav-2 knockout endothelial cells did not affect anti-proliferative effect of TGF-beta compared to empty vector. (PMID:22819829)
• CAV1 and -2 potentiate epsilon-toxin induced cytotoxicity by promoting toxin oligomerization (PMID:23056496)
• This study does not support an association between CAV2 variation and kidney transplant survival. (PMID:23667606)
• Our findings did not correspond with previous positive results, suggesting that CAV1-CAV2 variants studied in the present study are not important risk factors for Normal Tension Glaucoma. (PMID:23743525)
• This meta-analysis suggests that rs4236601[A] is associated with increased risk for POAG in Caucasian and Asian populations. (PMID:24034151)
• CAV1/CAV2 SNPs were associated significantly with primary open-angle glaucoma overall, particularly among women. (PMID:24572674)
• The implication of the caveolin genes, CAV1/CAV2, as a common genetic factor influencing both IOP variations and POAG may provide new insights of the underlying mechanism leading to glaucoma and glaucomatous visual field loss. (PMID:25525164)
• Results present initial characterization of key proteins Cav2 and CFL1 as cellular factors that colocalize with M in viral inclusions and filaments and ZNF502 protein which appears to interact with RSV M in the nucleus. (PMID:25556234)
• The minor allele G of rs17588172 in the CAV1-CAV2 locus is associated with decreased expression of CAV1 and CAV2 in some tissues, marginally with intraocular pressure elevation, and consequently with increased susceptibility to high-tension glaucoma. (PMID:26015768)
• variant in CAV2 is associated with increased age-of-onset of P. aeruginosa airway infection in cystic fibrosis cohort. (PMID:26047157)
• Caveolin-2 expression is necessary for the control of E2-dependent cellular proliferation of MCF-7 cells. (PMID:26480297)
• CAV-1 and -2 have roles in progression of prostate neoplasms (PMID:26543085)
• High CAV2 expression is associated with lung cancer. (PMID:26930711)
• this study confirmed the association of rs4236601 with primary open-angle glaucoma in different Chinese cohorts, and also found a common single-nucleotide polymorphism rs3801994 of diverse associations with primary open-angle glaucoma between Chinese and Japanese (PMID:27297022)
• A-type lamin-dependent Caveolin-2 homo-oligomerization in the inner nuclear membrane microdomain is a precondition for pY19-Caveolin-2-mediated insulin-response epigenetic activation at the nuclear periphery. (PMID:27552914)
• Results verified the presence of transcript III of cav-2 for the first time, but no protein associated was found. Also, a decreasing trend of cav-2 (transcripts I and II) were observed in tumoral tissues especially in stages I and II and seem to be associated with the incidence and promotion of breast cancer, especially in the initial stages of breast cancer. (PMID:28857238)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cav2	ENSDARG00000052000
mus_musculus	Cav2	ENSMUSG00000000058
rattus_norvegicus	Cav2	ENSRNOG00000057713
caenorhabditis_elegans		WBGENE00000301
caenorhabditis_elegans		WBGENE00000302

Paralogs (2): CAV1 (ENSG00000105974), CAV3 (ENSG00000182533)

Protein

Protein identifiers

Caveolin-2 — P51636 (reviewed: P51636)

All UniProt accessions (3): P51636, E9PCT3, Q53X57

UniProt curated annotations — full annotation on UniProt →

Function. May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. Acts as an accessory protein in conjunction with CAV1 in targeting to lipid rafts and driving caveolae formation. The Ser-36 phosphorylated form has a role in modulating mitosis in endothelial cells. Positive regulator of cellular mitogenesis of the MAPK signaling pathway. Required for the insulin-stimulated nuclear translocation and activation of MAPK1 and STAT3, and the subsequent regulation of cell cycle progression.

Subunit / interactions. Monomer or homodimer. Interacts with CAV1; the interaction forms a stable heterooligomeric complex that is required for targeting to lipid rafts and for caveolae formation. Tyrosine phosphorylated forms do not form heterooligomers with the Tyr-19-phosphorylated form existing as a monomer or dimer, and the Tyr-27-form as a monomer only. Interacts (tyrosine phosphorylated form) with the SH2 domain-containing proteins, RASA1, NCK1 and SRC. Interacts (tyrosine phosphorylated form) with INSR, the interaction (Tyr-27-phosphorylated form) is increased on insulin stimulation. Interacts (Tyr-19 phosphorylated form) with MAPK1 (phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation. Interacts with STAT3; the interaction is increased on insulin-induced tyrosine phosphorylation leading to STAT activation.

Subcellular location. Nucleus. Cytoplasm. Golgi apparatus membrane. Cell membrane. Membrane. Caveola.

Tissue specificity. Expressed in endothelial cells, smooth muscle cells, skeletal myoblasts and fibroblasts.

Post-translational modifications. Phosphorylated on serine and tyrosine residues. CAV1 promotes phosphorylation on Ser-23 which then targets the complex to the plasma membrane, lipid rafts and caveolae. Phosphorylation on Ser-36 appears to modulate mitosis in endothelial cells. Phosphorylation on both Tyr-19 and Tyr-27 is required for insulin-induced ‘Ser-727’ phosphorylation of STAT3 and its activation. Phosphorylation on Tyr-19 is required for insulin-induced phosphorylation of MAPK1 and DNA binding of STAT3. Tyrosine phosphorylation is induced by both EGF and insulin.

Miscellaneous. Produced by alternative initiation. Produced by alternative splicing.

Similarity. Belongs to the caveolin family.

Isoforms (3)

UniProt ID	Names	Canonical?
P51636-1	Alpha	yes
P51636-2	Beta
P51636-3	C

RefSeq proteins (4): NP_001193676, NP_001193677, NP_001224, NP_937855 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001612	Caveolin	Family
IPR018361	Caveolin_CS	Conserved_site

Pfam: PF01146

UniProt features (17 total): modified residue 5, mutagenesis site 4, splice variant 3, topological domain 2, chain 1, sequence variant 1, intramembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51636-F1	78.26	0.39

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 (5): 19, 20, 23, 27, 36

Mutagenesis-validated functional residues (4):

Position	Phenotype
19	greatly reduced src-mediated phosphorylation and binding of rasa1, src and nck1. completely eliminates src-mediated tyro
23	abolishes phosphorylation.
27	greatly reduced src-mediated phosphorylation and binding of rasa1, src and nck1. completely eliminates src-mediated phos
36	abolishes phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-162582	Signal Transduction
R-HSA-8939211	ESR-mediated signaling
R-HSA-9006931	Signaling by Nuclear Receptors

MSigDB gene sets: 382 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, TGGTGCT_MIR29A_MIR29B_MIR29C, MODULE_52, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, ZHAN_LATE_DIFFERENTIATION_GENES_UP, WANG_CLIM2_TARGETS_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, CHIBA_RESPONSE_TO_TSA_UP, GOBP_REGULATION_OF_NUCLEAR_DIVISION, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, GOBP_MEMBRANE_BIOGENESIS, GOCC_SECRETORY_GRANULE

GO Biological Process (26): endothelial cell proliferation (GO:0001935), negative regulation of endothelial cell proliferation (GO:0001937), positive regulation of endothelial cell proliferation (GO:0001938), vesicle fusion (GO:0006906), mitochondrion organization (GO:0007005), endoplasmic reticulum organization (GO:0007029), regulation of mitotic nuclear division (GO:0007088), transforming growth factor beta receptor signaling pathway (GO:0007179), G protein-coupled receptor signaling pathway (GO:0007186), insulin receptor signaling pathway (GO:0008286), skeletal muscle cell proliferation (GO:0014856), negative regulation of skeletal muscle cell proliferation (GO:0014859), vesicle organization (GO:0016050), receptor-mediated endocytosis of virus by host cell (GO:0019065), viral release from host cell (GO:0019076), cell differentiation (GO:0030154), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), positive regulation of MAPK cascade (GO:0043410), host-mediated activation of viral process (GO:0044794), obsolete vesicle docking (GO:0048278), skeletal muscle fiber development (GO:0048741), regulation of cytosolic calcium ion concentration (GO:0051480), positive regulation of dopamine receptor signaling pathway (GO:0060161), caveola assembly (GO:0070836), basement membrane organization (GO:0071711), cell population proliferation (GO:0008283)

GO Molecular Function (9): protein kinase binding (GO:0019901), protein-macromolecule adaptor activity (GO:0030674), D1 dopamine receptor binding (GO:0031748), heterotrimeric G-protein binding (GO:0032795), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), molecular adaptor activity (GO:0060090), scaffold protein binding (GO:0097110), protein binding (GO:0005515)

GO Cellular Component (16): Golgi membrane (GO:0000139), acrosomal membrane (GO:0002080), caveolar macromolecular signaling complex (GO:0002095), nucleus (GO:0005634), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), caveola (GO:0005901), focal adhesion (GO:0005925), transport vesicle (GO:0030133), cytoplasmic vesicle (GO:0031410), protein-containing complex (GO:0032991), plasma membrane raft (GO:0044853), membrane raft (GO:0045121), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
ESR-mediated signaling	1
Signaling by Nuclear Receptors	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle organization	3
cytoplasm	3
cellular anatomical structure	3
endothelial cell proliferation	2
regulation of endothelial cell proliferation	2
protein binding	2
protein dimerization activity	2
binding	2
intracellular membrane-bounded organelle	2
endomembrane system	2
epithelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
vesicle organization	1
vesicle-mediated transport	1
organelle membrane fusion	1
endomembrane system organization	1
regulation of mitotic cell cycle	1
regulation of cell cycle process	1
regulation of nuclear division	1
mitotic nuclear division	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
G protein-coupled receptor activity	1
signal transduction	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
striated muscle cell proliferation	1
negative regulation of cell population proliferation	1
skeletal muscle cell proliferation	1
regulation of skeletal muscle cell proliferation	1
receptor-mediated endocytosis	1
symbiont entry into host cell	1
endocytosis involved in viral entry into host cell	1
viral process	1
viral life cycle	1
exit from host cell	1
cellular developmental process	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1

Protein interactions and networks

STRING

1826 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAV2	CAV1	Q03135	985
CAV2	CAV3	P56539	899
CAV2	CAVIN1	Q6NZI2	879
CAV2	CACNA1B	Q00975	793
CAV2	CACNA1A	P78510	731
CAV2	CACNA1E	Q15878	725
CAV2	TMCO1	Q9UM00	696
CAV2	SCN10A	Q9Y5Y9	692
CAV2	CALML3	P27482	691
CAV2	CALML5	Q9NZT1	691
CAV2	CALML6	Q8TD86	682
CAV2	CALML4	Q96GE6	682
CAV2	ARHGAP24	Q8N264	678
CAV2	CACNA1C	Q13936	673
CAV2	CACNA1S	Q13698	668

IntAct

54 interactions, top by confidence:

A	B	Type	Score
MOB1B	LATS1	psi-mi:“MI:0914”(association)	0.840
EGFR	GAPDH	psi-mi:“MI:0914”(association)	0.790
STBD1	GABARAP	psi-mi:“MI:0914”(association)	0.760
CAV1	CAV2	psi-mi:“MI:0915”(physical association)	0.740
EGFR	CAV2	psi-mi:“MI:0915”(physical association)	0.670
CAV2	EGFR	psi-mi:“MI:0915”(physical association)	0.670
CAV1	CAVIN2	psi-mi:“MI:0914”(association)	0.600
SDCBP	CAV2	psi-mi:“MI:0915”(physical association)	0.560
TMEM184A	SLC33A1	psi-mi:“MI:0914”(association)	0.530
REEP1	PLSCR1	psi-mi:“MI:0914”(association)	0.530
TMEM43	ENDOD1	psi-mi:“MI:0914”(association)	0.530
M	CAV2	psi-mi:“MI:0915”(physical association)	0.400
VKORC1	CAV2	psi-mi:“MI:0915”(physical association)	0.400
TAS2R31	CAV2	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
DNAJA1	CAV2	psi-mi:“MI:0915”(physical association)	0.370
CAV2		psi-mi:“MI:0915”(physical association)	0.370
CAV2	SURF4	psi-mi:“MI:0914”(association)	0.350
CAV2	CYB5B	psi-mi:“MI:0914”(association)	0.350
	DENND11	psi-mi:“MI:0914”(association)	0.350
rep	GPR89A	psi-mi:“MI:0914”(association)	0.350
M	DENND11	psi-mi:“MI:0914”(association)	0.350
C5AR1	SLC12A8	psi-mi:“MI:0914”(association)	0.350
ACKR2	TMEM223	psi-mi:“MI:0914”(association)	0.350
SPPL2B	HAS3	psi-mi:“MI:0914”(association)	0.350
YIPF3	EI24	psi-mi:“MI:0914”(association)	0.350
VIPR2	EI24	psi-mi:“MI:0914”(association)	0.350
P2RY2	SCAMP3	psi-mi:“MI:0914”(association)	0.350
EDNRA	MGST3	psi-mi:“MI:0914”(association)	0.350
TMEM72	MGST3	psi-mi:“MI:0914”(association)	0.350

BioGRID (140): CAV2 (Two-hybrid), CAV2 (PCA), EGFR (Reconstituted Complex), CAV2 (Proximity Label-MS), SDCBP (Two-hybrid), CAV2 (Affinity Capture-MS), CAV2 (Affinity Capture-MS), CAV2 (Affinity Capture-MS), CAV2 (Affinity Capture-MS), CAV1 (Affinity Capture-Western), DIABLO (Affinity Capture-MS), RAB35 (Affinity Capture-MS), RAB1B (Affinity Capture-MS), CYB5B (Affinity Capture-MS), IVNS1ABP (Affinity Capture-MS)

ESM2 similar proteins: A0M8R5, A0M8R6, A0M8S6, A1X148, O46550, P41350, P51636, Q00PK0, Q03135, Q07DV9, Q07DW0, Q07DX2, Q07DY2, Q07DZ2, Q07DZ3, Q07E26, Q07E39, Q07E50, Q09YH8, Q09YH9, Q09YJ1, Q09YK2, Q09YL4, Q09YN7, Q108U8, Q2IBA4, Q2IBA5, Q2IBC1, Q2IBC2, Q2IBC5, Q2IBD6, Q2IBD7, Q2IBF0, Q2IBF3, Q2IBG9, Q2QL80, Q2QL91, Q2QLB1, Q2QLC1, Q2QLC2

Diamond homologs: A0M8R5, A0M8R6, A0M8S6, A0M8S7, A1X148, A1X149, O46550, P33724, P35431, P41350, P49817, P51636, P51637, P51638, P56539, P79132, Q00PJ9, Q00PK0, Q03135, Q07DV9, Q07DW0, Q07DX1, Q07DX2, Q07DY2, Q07DZ2, Q07DZ3, Q07E02, Q07E25, Q07E26, Q07E38, Q07E39, Q07E49, Q07E50, Q09YH8, Q09YH9, Q09YJ1, Q09YK1, Q09YK2, Q09YL4, Q09YN6

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
CSNK2A1	“up-regulates activity”	CAV2	phosphorylation
SRC	down-regulates	CAV2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

276 predictions. Top by Δscore:

Variant	Effect	Δscore
7:116499927:TCAAG:T	donor_loss	0.9900
7:116499930:AGG:A	donor_loss	0.9900
7:116499932:GTG:G	donor_loss	0.9900
7:116499933:T:G	donor_loss	0.9900
7:116505965:TTCCA:T	acceptor_loss	0.9900
7:116505966:TCCAG:T	acceptor_loss	0.9900
7:116505967:CCAG:C	acceptor_loss	0.9900
7:116505968:CA:C	acceptor_loss	0.9900
7:116505969:A:AG	acceptor_gain	0.9900
7:116505969:A:C	acceptor_loss	0.9900
7:116505969:AG:A	acceptor_gain	0.9900
7:116505970:G:GG	acceptor_gain	0.9900
7:116505970:GG:G	acceptor_gain	0.9900
7:116505970:GGATT:G	acceptor_gain	0.9800
7:116500359:AT:A	donor_gain	0.9600
7:116505970:GGAT:G	acceptor_gain	0.9600
7:116499934:G:GT	donor_gain	0.9400
7:116500258:AGCT:A	acceptor_gain	0.9400
7:116500259:GCTG:G	acceptor_gain	0.9400
7:116500602:C:T	donor_gain	0.9400
7:116499475:G:GT	donor_gain	0.9300
7:116499896:G:GT	donor_gain	0.9200
7:116500258:AGCTG:A	acceptor_gain	0.9000
7:116500259:GCT:G	acceptor_gain	0.9000
7:116500259:GCTGG:G	acceptor_gain	0.9000
7:116500445:CTGG:C	donor_loss	0.9000
7:116500446:TGG:T	donor_loss	0.9000
7:116500447:GGTGA:G	donor_loss	0.9000
7:116500448:GTGAG:G	donor_loss	0.9000
7:116500449:TGAGA:T	donor_loss	0.9000

AlphaMissense

1078 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:116500326:A:C	S73R	0.997
7:116500328:C:A	S73R	0.997
7:116500328:C:G	S73R	0.997
7:116500338:T:C	F77L	0.993
7:116500340:T:A	F77L	0.993
7:116500340:T:G	F77L	0.993
7:116500411:G:A	G101E	0.993
7:116506071:A:C	S147R	0.993
7:116506073:C:A	S147R	0.993
7:116506073:C:G	S147R	0.993
7:116500347:A:C	S80R	0.992
7:116500349:C:A	S80R	0.992
7:116500349:C:G	S80R	0.992
7:116500446:T:A	W113R	0.992
7:116500446:T:C	W113R	0.992
7:116500266:T:C	F53L	0.991
7:116500268:C:A	F53L	0.991
7:116500268:C:G	F53L	0.991
7:116500303:C:T	S65F	0.991
7:116500410:G:A	G101R	0.990
7:116500410:G:C	G101R	0.990
7:116500319:G:C	W70C	0.987
7:116500319:G:T	W70C	0.987
7:116500434:T:C	C109R	0.987
7:116500286:G:C	E59D	0.986
7:116500286:G:T	E59D	0.986
7:116500399:C:A	A97D	0.986
7:116505982:C:A	P117H	0.986
7:116500387:C:A	A93D	0.985
7:116500267:T:G	F53C	0.984

dbSNP variants (sampled 300 via entrez): RS1000089535 (7:116498109 T>C), RS1000279184 (7:116497771 G>A,C), RS1000304686 (7:116501386 C>G), RS1000440118 (7:116501053 A>T), RS1000644615 (7:116499057 C>T), RS1000700989 (7:116505804 G>A), RS1000750569 (7:116507109 A>G), RS1000773167 (7:116499266 A>C,G), RS1000774739 (7:116505525 C>T), RS1000814774 (7:116508373 A>T), RS1001244549 (7:116504372 A>C,G), RS1001517479 (7:116501896 C>T), RS1001714010 (7:116504861 TAAC>T), RS1001753189 (7:116502501 A>G), RS1001851074 (7:116500200 C>G)

Disease associations

OMIM: gene MIM:601048 | disease phenotypes:

GenCC curated gene-disease

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
amyotrophic lateral sclerosis	Limited	AD

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

44 associations (top):

Study	Trait	p-value
GCST000562_1	PR interval	4.000000e-28
GCST000793_1	Glaucoma (primary open-angle)	2.000000e-11
GCST002535_4	PR interval	3.000000e-14
GCST002580_4	Intraocular pressure	2.000000e-11
GCST002582_6	Glaucoma (primary open-angle)	5.000000e-07
GCST004074_7	Intraocular pressure	1.000000e-11
GCST004074_8	Intraocular pressure	4.000000e-13
GCST004826_17	P wave duration	1.000000e-10
GCST004826_8	P wave duration	8.000000e-11
GCST005080_8	PR interval	2.000000e-18
GCST005580_109	Intraocular pressure	1.000000e-42
GCST005580_131	Intraocular pressure	2.000000e-48
GCST005787_25	Heart rate response to exercise	4.000000e-08
GCST005787_9	Heart rate response to exercise	3.000000e-11
GCST005788_9	Heart rate response to recovery post exercise	7.000000e-10
GCST005845_5	Heart rate increase in response to exercise	2.000000e-09
GCST005846_8	Heart rate response to recovery post exercise (10 sec)	2.000000e-12
GCST005847_10	Heart rate response to recovery post exercise (20 sec)	2.000000e-12
GCST005848_16	Heart rate response to recovery post exercise (50 sec)	3.000000e-10
GCST005849_1	Heart rate response to recovery post exercise (40 sec)	8.000000e-11
GCST005850_7	Heart rate response to recovery post exercise (30 sec)	2.000000e-12
GCST006061_144	Atrial fibrillation	8.000000e-32
GCST006065_34	Glaucoma (primary open-angle)	4.000000e-12
GCST006394_14	Intraocular pressure	2.000000e-55
GCST006395_22	Glaucoma	9.000000e-12
GCST006395_40	Glaucoma	1.000000e-11
GCST006412_70	Intraocular pressure	3.000000e-56
GCST006414_125	Atrial fibrillation	2.000000e-55
GCST007045_6	PR interval	9.000000e-69
GCST009302_11	Antipsychotic drug-induced weight gain in schizophrenia	2.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval
EFO:0004695	intraocular pressure measurement
EFO:0005094	P wave duration
EFO:0009184	heart rate response to exercise
EFO:0009185	heart rate response to recovery post exercise
EFO:0004567	antipsychotic drug related weight gain
EFO:0004644	TPE interval measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, increases methylation	7
Arsenic Trioxide	decreases expression, increases expression, affects cotreatment	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
chloropicrin	affects expression, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Dexamethasone	increases expression, affects cotreatment, decreases expression	2
Estradiol	affects cotreatment, decreases expression	2
Fluorouracil	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	2
Cyclosporine	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Particulate Matter	increases abundance, affects cotreatment, increases expression, affects expression, decreases expression	2
FR900359	increases phosphorylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
bisphenol A diglycidyl ether	decreases reaction, increases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
triadimefon	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1AJ	Ubigene PANC-1 CAV2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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