CAVIN1

Summary

CAVIN1 (caveolae associated protein 1, HGNC:9688) is a protein-coding gene on chromosome 17q21.2, encoding Caveolae-associated protein 1 (Q6NZI2). Plays an important role in caveolae formation and organization.

This gene encodes a protein that enables the dissociation of paused ternary polymerase I transcription complexes from the 3’ end of pre-rRNA transcripts. This protein regulates rRNA transcription by promoting the dissociation of transcription complexes and the reinitiation of polymerase I on nascent rRNA transcripts. This protein also localizes to caveolae at the plasma membrane and is thought to play a critical role in the formation of caveolae and the stabilization of caveolins. This protein translocates from caveolae to the cytoplasm after insulin stimulation. Caveolae contain truncated forms of this protein and may be the site of phosphorylation-dependent proteolysis. This protein is also thought to modify lipid metabolism and insulin-regulated gene expression. Mutations in this gene result in a disorder characterized by generalized lipodystrophy and muscular dystrophy.

Source: NCBI Gene 284119 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lipodystrophy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 184 total — 10 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 47
• MANE Select transcript: NM_012232

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9688
Approved symbol	CAVIN1
Name	caveolae associated protein 1
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	cavin-1, CGL4
Ensembl gene	ENSG00000177469
Ensembl biotype	protein_coding
OMIM	603198
Entrez	284119

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000357037, ENST00000870236, ENST00000944722, ENST00000944723

RefSeq mRNA: 1 — MANE Select: NM_012232 NM_012232

CCDS: CCDS11425

Canonical transcript exons

ENST00000357037 — 2 exons

Exon	Start	End
ENSE00001402213	42422627	42423256
ENSE00001414514	42402449	42405388

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 99.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 149.3503 / max 1372.4879, expressed in 1580 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166165	115.6524	1571
166163	12.8824	1055
166164	10.1777	1147
166162	9.9216	999
166160	0.7162	403

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right coronary artery	UBERON:0001625	99.45	gold quality
tendon of biceps brachii	UBERON:0008188	99.40	gold quality
popliteal artery	UBERON:0002250	99.37	gold quality
tibial artery	UBERON:0007610	99.37	gold quality
aorta	UBERON:0000947	99.34	gold quality
descending thoracic aorta	UBERON:0002345	99.32	gold quality
ascending aorta	UBERON:0001496	99.30	gold quality
thoracic aorta	UBERON:0001515	99.30	gold quality
saphenous vein	UBERON:0007318	99.30	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.27	gold quality
lower esophagus	UBERON:0013473	99.25	gold quality
coronary artery	UBERON:0001621	99.24	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.23	gold quality
left coronary artery	UBERON:0001626	99.22	gold quality
body of uterus	UBERON:0009853	99.19	gold quality
mucosa of stomach	UBERON:0001199	99.15	gold quality
calcaneal tendon	UBERON:0003701	99.14	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.13	gold quality
left uterine tube	UBERON:0001303	99.11	gold quality
smooth muscle tissue	UBERON:0001135	99.10	gold quality
synovial joint	UBERON:0002217	99.10	gold quality
tibial nerve	UBERON:0001323	99.07	gold quality
adipose tissue	UBERON:0001013	99.06	gold quality
apex of heart	UBERON:0002098	99.05	gold quality
tendon	UBERON:0000043	99.03	gold quality
blood vessel layer	UBERON:0004797	99.00	gold quality
myometrium	UBERON:0001296	98.99	gold quality
omental fat pad	UBERON:0010414	98.99	gold quality
peritoneum	UBERON:0002358	98.98	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.97	gold quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 24.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	422.25
E-MTAB-8271	yes	412.50
E-MTAB-8530	yes	312.97
E-GEOD-83139	yes	145.45
E-MTAB-8142	yes	93.39
E-HCAD-1	yes	74.87
E-MTAB-8410	yes	52.26
E-GEOD-134144	yes	45.70
E-CURD-46	yes	35.79
E-HCAD-10	yes	34.31
E-MTAB-6701	yes	30.76
E-MTAB-6678	yes	28.48
E-HCAD-31	yes	25.02
E-HCAD-11	yes	21.21
E-HCAD-9	yes	18.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1

miRNA regulators (miRDB)

86 targeting CAVIN1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-6832-5P	99.58	64.82	1132

Literature-anchored findings (GeneRIF, showing 40)

• Caveolae of human adipocytes are proposed to function in targeting, relocation and proteolytic control of PTRF and other PEST-domain-containing signalling proteins (PMID:15242332)
• The findings indicate also a novel extranuclear function for PTRF in the control of lipolysis. (PMID:17026959)
• identified PTRF mutations in 5 nonconsanguineous patients who presented with both generalized lipodystrophy and muscular dystrophy (PMID:19726876)
• PTRF-CAVIN deficiency thus presents the phenotypic spectrum caused by a quintessential lack of functional caveolae. (PMID:20300641)
• These data demonstrate a new function for PTRF/cavin-1, a new functional interaction between caveolin-1 and Rab8 and that actomyosin interactions can induce tension on caveolin-1-containing membranes. (PMID:20427576)
• mutations in PTRF result in a novel phenotype that includes generalized lipodystrophy with mild metabolic derangements, myopathy, cardiac arrhythmias, atlantoaxial instability, and pyloric stenosis (PMID:20684003)
• PTRF/cavin-1-expressing PC3 cells exhibit decreased migration, and that this effect is mediated by reduced MMP9 production. (PMID:20732728)
• Findings suggest that Cav-1 and PTRF/Cavin could represent two relevant and distinct targets to modulate IGF-IR function. (PMID:21152401)
• membrane-delimited interaction between MG53 and PTRF contributes to initiation of cell membrane repair (PMID:21343302)
• PTRF expression is increased in senescent human fibroblasts. (PMID:21445100)
• This study identified no pathogenic mutations in BAG3, MATR3, PTRF or TCAP in Australian muscular dystrophy. (PMID:21683594)
• PTRF/cavin-1 is a novel regulator of oxidative stress-induced premature senescence by acting as a link between free radicals and activation of the p53/p21(Waf1/Cip1) pathway. (PMID:21705337)
• The cavin family protein Polymerase 1 and transcript release factor, SRBC and serum deprivation response protein were down regulated in breast cancer cell lines and breast tumor tissue. (PMID:21913217)
• Data show that two proteins, PTRF/cavin-1 and MIF, which are differentially expressed between normal lung and non-small cell lung cancer. (PMID:22461895)
• PTRF/cavin-1 is essential for multidrug resistance in cancer cells via the fortification of lipid rafts. (PMID:23214712)
• PTRF and Cav-1 can bind IGF-IR and regulate IGF-IR internalization and plasma membrane replacement, mechanisms frequently deregulated in cancer cells.[review] (PMID:23404184)
• The tumor-promoting role of cavin-1 in pancreatic cancer was found to be largely dependent on caveolin-1. (PMID:23770857)
• caveolin-1 in advanced prostate cancer is present outside of caveolae, because of the lack of cavin-1 expression (PMID:23934189)
• In this review stromal PTRF expression decreases with progression of prostate cancer disease. (PMID:23938946)
• Rather than forming a single coat complex containing the three cavin family members, single-molecule analysis reveals an exquisite specificity of interactions between cavin1, cavin2 and cavin3. (PMID:24473072)
• PTRF acts as a modulator in GBM chemoresistance (PMID:24747515)
• In human adipose tissue, PTRF mRNA levels positively correlated with markers of lipolysis and cellular senescence. A negative relationship between telomere length and PTRF mRNA levels was observed in human subcutaneous fat. (PMID:24812087)
• cavin3 is recruited to the caveolae coat by cavin1 to interact with caveolin1 and regulate the duration time of caveolae at the plasma membrane. (PMID:25588833)
• this study presents a novel mutation of PTRF from Saudi Arabia and our findings broaden the mutation spectrum of PTRF in the familial CGL4 phenotype. (PMID:25721873)
• Using in silico and in vitro analysis we show that Cavin-1 is expressed in myogenic Rhabdomyosarcoma tumors and human and primary mouse RMS cultures. Cavin-1 or Cav-1 knockdown led to impairment of cell proliferation and migration. (PMID:25822667)
• The presence of caveolae as an anatomic structure is not sufficient to ensure their proper function in patient with PTRF mutation. (PMID:25904680)
• Our data support a role for PTRF/cavin-1, through caveolae formation, as an attenuator of the non-caveolar functionality of Cav1 in Gal3-Cav1 signalling and regulation of focal adhesion dynamics and cancer cell migration. (PMID:25942420)
• Cavin-1 and cavin-2 are strongly expressed within caveolae-like structures within liver sinusoidal endothelial cells of the hepatitis C-related cirrhotic liver and cavin-1 would play a critical role in regulating aspects of caveolin-1. (PMID:26086560)
• This study reports an unanticipated function of ROR1 as a scaffold of cavin-1 and caveolin-1, two essential structural components of caveolae. (PMID:26725982)
• A homozygous PTRF mutation was identified in patient-1. Congenital generalized lipodystrophy type 4 was caused by homozygous PTRF c.481-482insGTGA (p.Lys161Serfs*41) mutation in patient-2. (PMID:27167729)
• PTRF inhibits the proliferation, migration, and invasion of colorectal cancer cells. Future studies need to define the role of PTRF in the regulation of chemo-resistance in colorectal cancer cells and in colorectal cancer stem cells. (PMID:27203393)
• The expression of the PTRF protein was significantly weaker than that in the adjacent normal lung tissues using immunohistochemical staining. The findings revealed that miR187 promotes cell growth and invasion by targeting PTRF and miR187 may be a new prognostic factor for nonsmall cell lung cancer (PMID:27634346)
• Purified Cavin1 60S complexes were analyzed structurally in solution and after liposome reconstitution by electron cryotomography. Cavin1 adopted a flexible, net-like protein mesh able to form polyhedral lattices on phosphatidylserine-containing vesicles. Mutating the two coiled-coil domains in Cavin1 revealed that they mediate distinct assembly steps during 60S complex formation. (PMID:27834731)
• DNA methylation profiling identifies PTRF/Cavin-1 as a novel tumor suppressor in Ewing sarcoma when co-expressed with caveolin-1, which PTRF, disrupts the MDM2/p53 complex, leading to apoptosis. (PMID:27894957)
• Results show that PTRF is a direct target of miR-187. PTRF plays crucial roles in miR-187-induced epithelial-mesenchymal transition and migration of non-small cell lung cancer cells. (PMID:28393200)
• Data suggest that the predominant plasmalemmal anionic lipid phosphatidylserine is essential for proper caveolin/cavin clustering, caveola formation, and caveola dynamics; membrane scrambling (by using other phospholipids) can perturb caveolar stability; these studies involved caveolin-1 and cavin-1 as models of caveolin/cavin clustering. (PMID:28698382)
• Overexpressing PTRF induced the malignancy of nearby cells in vivo, suggesting that PTRF alters the microenvironment through intercellular communication via exosomes in glioblastoma. (PMID:29556340)
• Data suggest that PTRF is present in the bloodstream and associates with exosomes; visceral adipose tissue may be a source of plasma PTRF; PTRF is rapidly processed inside adipocytes and promotes glucose absorption in adipocytes. (PMID:29869069)
• High CAVIN1 expression is associated with glioblastoma. (PMID:30949900)
• Overexpression of PTRF led to MAPK inhibitors (MAPKi) resistance in melanoma, increased cell adhesion and sphere formation. In addition, immunohistochemistry of patient samples showed that PTRF expression levels were a significant biomarker of poor progression-free survival. (PMID:31267558)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cavin1b	ENSDARG00000059362
danio_rerio	cavin1a	ENSDARG00000076411
mus_musculus	Cavin1	ENSMUSG00000004044
rattus_norvegicus	Cavin1	ENSRNOG00000019778

Paralogs (3): CAVIN2 (ENSG00000168497), CAVIN4 (ENSG00000170681), CAVIN3 (ENSG00000170955)

Protein

Protein identifiers

Caveolae-associated protein 1 — Q6NZI2 (reviewed: Q6NZI2)

Alternative names: Cavin-1, Polymerase I and transcript release factor

All UniProt accessions (1): Q6NZI2

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in caveolae formation and organization. Essential for the formation of caveolae in all tissues. Core component of the CAVIN complex which is essential for recruitment of the complex to the caveolae in presence of calveolin-1 (CAV1). Essential for normal oligomerization of CAV1. Promotes ribosomal transcriptional activity in response to metabolic challenges in the adipocytes and plays an important role in the formation of the ribosomal transcriptional loop. Dissociates transcription complexes paused by DNA-bound TTF1, thereby releasing both RNA polymerase I and pre-RNA from the template. The caveolae biogenesis pathway is required for the secretion of proteins such as GASK1A.

Subunit / interactions. Component of the CAVIN complex composed of CAVIN1, CAVIN2, CAVIN3 and CAVIN4. Homotrimer. Interacts with TTF1. Interacts with RNA polymerase I subunit POLR1A/RPA1. Binds the 3’ end of pre-rRNA. Interacts with transcription factor ZNF148. Interacts with LIPE in the adipocyte cytoplasm. Interacts with CAV1 and CAVIN3. Interacts with CAVIN2. Interacts with CAVIN4 and CAV3.

Subcellular location. Membrane. Caveola. Cell membrane. Microsome. Endoplasmic reticulum. Cytoplasm. Cytosol. Mitochondrion. Nucleus.

Post-translational modifications. Phosphorylated. Present in active and inactive forms. Changes in phosphorylation pattern may alter activity. Phosphorylation at Tyr-156 is essential for its functionin the regulation of ribosomal transcriptional activity. Five truncated forms are found in the caveolae. These are thought to be the result of proteolysis and may be phosphorylation-dependent. Monoubiquitinated.

Disease relevance. Lipodystrophy, congenital generalized, 4 (CGL4) [MIM:613327] A form of congenital generalized lipodystrophy, a metabolic disorder characterized by a near complete absence of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and diabetes mellitus. CGL4 is characterized by the association of congenital generalized lipodystrophy with muscular dystrophy and cardiac anomalies. Inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The leucine-zipper domain 1 is essential for its localization in the caveolae.

Similarity. Belongs to the CAVIN family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6NZI2-1	1	yes
Q6NZI2-2	2
Q6NZI2-3	3

RefSeq proteins (1): NP_036364* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026752	Cavin_fam	Family

Pfam: PF15237

UniProt features (51 total): modified residue 20, region of interest 10, cross-link 7, compositionally biased region 4, sequence conflict 3, splice variant 2, sequence variant 2, chain 1, coiled-coil region 1, helix 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9EGN	X-RAY DIFFRACTION	1.57
9EG6	X-RAY DIFFRACTION	3.2
9EIU	X-RAY DIFFRACTION	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NZI2-F1	68.03	0.24

Antibody-complex structures (SAbDab): 3 — 9EG6, 9EGN, 9EIU

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 (27): 1, 36, 40, 46, 118, 156, 167, 169, 171, 175, 202, 203, 300, 302, 308, 365, 366, 379, 387, 389 …

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-73863	RNA Polymerase I Transcription Termination
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-73864	RNA Polymerase I Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 358 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, MODULE_52, TGCGCANK_UNKNOWN, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, LFA1_Q6, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, TOMLINS_PROSTATE_CANCER_DN, ADDYA_ERYTHROID_DIFFERENTIATION_BY_HEMIN, GGGTGGRR_PAX4_03, GOBP_RRNA_TRANSCRIPTION, MODULE_118, BROWNE_HCMV_INFECTION_48HR_DN

GO Biological Process (6): transcription initiation at RNA polymerase I promoter (GO:0006361), termination of RNA polymerase I transcription (GO:0006363), rRNA transcription (GO:0009303), protein secretion (GO:0009306), positive regulation of cell motility (GO:2000147), DNA-templated transcription termination (GO:0006353)

GO Molecular Function (5): RNA binding (GO:0003723), rRNA primary transcript binding (GO:0042134), identical protein binding (GO:0042802), protein binding (GO:0005515), rRNA binding (GO:0019843)

GO Cellular Component (11): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), caveola (GO:0005901), protein-containing complex (GO:0032991), membrane raft (GO:0045121), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
RHO GTPase cycle	3
RNA Polymerase I Transcription	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Gene expression (Transcription)	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membrane-bounded organelle	3
cytoplasm	3
transcription by RNA polymerase I	2
DNA-templated transcription	2
DNA-templated transcription initiation	1
DNA-templated transcription termination	1
rRNA metabolic process	1
protein transport	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
positive regulation of locomotion	1
positive regulation of cellular process	1
cell motility	1
regulation of cell motility	1
RNA biosynthetic process	1
nucleic acid binding	1
rRNA binding	1
protein binding	1
binding	1
RNA binding	1
nuclear lumen	1
intracellular anatomical structure	1
endomembrane system	1
membrane	1
cell periphery	1
plasma membrane raft	1
cellular_component	1
membrane microdomain	1

Protein interactions and networks

STRING

1644 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAVIN1	CAV1	Q03135	997
CAVIN1	CAV3	P56539	955
CAVIN1	CAV2	P51636	879
CAVIN1	BSCL2	Q96G97	858
CAVIN1	AGPAT2	O15120	840
CAVIN1	GHDC	Q8N2G8	818
CAVIN1	EHD2	Q9NZN4	807
CAVIN1	TRIM72	Q6ZMU5	780
CAVIN1	PACSIN2	Q9UNF0	776
CAVIN1	EHD3	Q9NZN3	769
CAVIN1	DYSF	O75923	753
CAVIN1	HCRT	O43612	723
CAVIN1	CAVIN3	Q969G5	717
CAVIN1	POLI	Q9UNA4	703
CAVIN1	DAG1	Q14118	689

IntAct

262 interactions, top by confidence:

A	B	Type	Score
CAVIN1	FBXO28	psi-mi:“MI:0915”(physical association)	0.800
CAVIN1	CAVIN3	psi-mi:“MI:0915”(physical association)	0.770
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CAVIN1	CAVIN1	psi-mi:“MI:0915”(physical association)	0.700
DNTTIP2	CAVIN1	psi-mi:“MI:0915”(physical association)	0.680
CAVIN1	CAV3	psi-mi:“MI:0915”(physical association)	0.670
SPANXN2	CAVIN1	psi-mi:“MI:0915”(physical association)	0.670
CAVIN1	ZCCHC10	psi-mi:“MI:0915”(physical association)	0.670
CAVIN3	CAV1	psi-mi:“MI:0914”(association)	0.650
CAV1	CAVIN1	psi-mi:“MI:0915”(physical association)	0.640
CAV1	CAVIN1	psi-mi:“MI:0914”(association)	0.640
CAVIN1	CAV1	psi-mi:“MI:0914”(association)	0.640
CAVIN1	CAV1	psi-mi:“MI:0915”(physical association)	0.640
CAV1	CAVIN2	psi-mi:“MI:0914”(association)	0.600
CAVIN2	CAV1	psi-mi:“MI:0914”(association)	0.600
CAVIN1	YAF2	psi-mi:“MI:0915”(physical association)	0.560
CAVIN1	ZSCAN21	psi-mi:“MI:0915”(physical association)	0.560
TSGA10IP	CAVIN1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (398): PTRF (Affinity Capture-MS), PTRF (Affinity Capture-MS), PTRF (Affinity Capture-MS), PTRF (Affinity Capture-MS), PTRF (Affinity Capture-MS), PTRF (Affinity Capture-MS), PTRF (Affinity Capture-MS), PTRF (Affinity Capture-MS), PTRF (Affinity Capture-MS), PTRF (Affinity Capture-MS), PTRF (Affinity Capture-MS), PTRF (Affinity Capture-MS), PTRF (Affinity Capture-MS), PTRF (Affinity Capture-MS), PTRF (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RR37, A1L170, A1L1I3, A1L260, A2AMM0, A4IFJ0, B5G1P1, D3ZQL6, E7F5E1, G5BQH4, O08919, O54724, O60237, O75420, P06759, P33622, P53814, P85125, Q2KI85, Q2TAL5, Q3T044, Q3UMT1, Q4RTJ5, Q4V882, Q5I1X5, Q5U2R6, Q63312, Q6NZI2, Q75AS0, Q80VC9, Q8BG95, Q8BGT6, Q8C0J6, Q8CI12, Q8IV56, Q8K382, Q8N3F8, Q8TEH3, Q8WUF5, Q91VJ2

Diamond homologs: A1L260, A2AMM0, A2VDA9, A4FV37, A5PJI6, B1PRL5, O54724, O95810, P85125, Q5BKX8, Q63918, Q66H98, Q6NZI2, Q969G5, Q9Z1H9, Q91VJ2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 156 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
RHOQ GTPase cycle	6	11.7×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein transport	15	5.3×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	5
Uncertain significance	95
Likely benign	37
Benign	21

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
2506963	NM_012232.6(CAVIN1):c.259C>T (p.Gln87Ter)	Pathogenic
30327	NM_012232.6(CAVIN1):c.135del (p.Lys45fs)	Pathogenic
30328	NM_012232.6(CAVIN1):c.478_481dup (p.Lys161fs)	Pathogenic
30330	NM_012232.6(CAVIN1):c.471+1G>T	Pathogenic
3063854	NM_012232.6(CAVIN1):c.141_148del (p.Asp47fs)	Pathogenic
4790660	NM_012232.6(CAVIN1):c.462del (p.Met154fs)	Pathogenic
6601	NM_012232.6(CAVIN1):c.696dup (p.Lys233fs)	Pathogenic
6602	NM_012232.6(CAVIN1):c.526del (p.Glu176fs)	Pathogenic
6603	NM_012232.6(CAVIN1):c.160del (p.Val54fs)	Pathogenic
6604	NM_012232.6(CAVIN1):c.362dup (p.Lys122fs)	Pathogenic
2633945	NM_012232.6(CAVIN1):c.459_462delinsAAT (p.Met154fs)	Likely pathogenic
3236450	NM_012232.6(CAVIN1):c.512C>A (p.Ser171Ter)	Likely pathogenic
3764538	NM_012232.6(CAVIN1):c.1061_1091del (p.Glu354fs)	Likely pathogenic
501498	NM_012232.6(CAVIN1):c.199C>T (p.Gln67Ter)	Likely pathogenic
982092	NM_012232.6(CAVIN1):c.550G>T (p.Glu184Ter)	Likely pathogenic

SpliceAI

226 predictions. Top by Δscore:

Variant	Effect	Δscore
17:42405389:CTAAG:C	acceptor_loss	1.0000
17:42405390:T:G	acceptor_loss	1.0000
17:42422621:GCTCA:G	donor_loss	1.0000
17:42422622:CTCA:C	donor_loss	1.0000
17:42422623:TCAC:T	donor_loss	1.0000
17:42422624:CACC:C	donor_loss	1.0000
17:42422625:ACCT:A	donor_loss	1.0000
17:42405385:CATC:C	acceptor_gain	0.9900
17:42405387:TC:T	acceptor_gain	0.9900
17:42405388:CC:C	acceptor_gain	0.9900
17:42405389:C:CC	acceptor_gain	0.9900
17:42412053:C:CA	donor_gain	0.9800
17:42422625:A:AC	donor_gain	0.9700
17:42422626:C:CC	donor_gain	0.9700
17:42405384:TCATC:T	acceptor_gain	0.9600
17:42405385:CATCC:C	acceptor_gain	0.9600
17:42405386:ATC:A	acceptor_gain	0.9500
17:42405389:C:T	acceptor_gain	0.9300
17:42412052:TCC:T	donor_gain	0.9300
17:42412053:CCC:C	donor_gain	0.9300
17:42405386:ATCCT:A	acceptor_gain	0.8700
17:42409463:A:T	donor_gain	0.8700
17:42412054:C:CT	donor_gain	0.8700
17:42407247:C:CA	donor_gain	0.8600
17:42412057:CCGG:C	donor_gain	0.8000
17:42412050:ACT:A	donor_gain	0.7900
17:42412051:CTC:C	donor_gain	0.7900
17:42409501:TAC:T	donor_gain	0.7700
17:42409502:ACA:A	donor_gain	0.7700
17:42409503:CAC:C	donor_gain	0.7700

AlphaMissense

2528 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:42422646:A:G	F151S	1.000
17:42422664:A:G	L145P	1.000
17:42422685:A:G	L138P	1.000
17:42422925:A:G	L58P	1.000
17:42422928:A:G	L57P	1.000
17:42404891:G:C	F323L	0.999
17:42404891:G:T	F323L	0.999
17:42404892:A:G	F323S	0.999
17:42404893:A:G	F323L	0.999
17:42422640:A:T	V153D	0.999
17:42422645:A:C	F151L	0.999
17:42422645:A:T	F151L	0.999
17:42422647:A:G	F151L	0.999
17:42422874:A:G	L75P	0.999
17:42422895:A:C	I68S	0.999
17:42422895:A:G	I68T	0.999
17:42422916:A:C	I61S	0.999
17:42422925:A:T	L58Q	0.999
17:42404886:A:T	V325D	0.998
17:42422646:A:C	F151C	0.998
17:42422655:C:G	R148P	0.998
17:42422661:A:G	L146P	0.998
17:42422744:G:C	S118R	0.998
17:42422744:G:T	S118R	0.998
17:42422746:T:G	S118R	0.998
17:42422769:A:G	L110P	0.998
17:42422820:A:G	L93P	0.998
17:42422865:C:G	R78P	0.998
17:42422895:A:T	I68N	0.998
17:42422908:C:G	A64P	0.998

dbSNP variants (sampled 300 via entrez): RS1000076954 (17:42407644 C>A,T), RS1000145279 (17:42423846 A>G), RS1000346204 (17:42421164 C>A,G), RS1000428246 (17:42414319 T>C), RS1000727800 (17:42419305 G>A), RS1000820765 (17:42407312 AT>A), RS1000832156 (17:42406981 G>A), RS1001078211 (17:42419536 A>G), RS1001335547 (17:42403001 C>A,T), RS1001402812 (17:42422332 G>C), RS1001487281 (17:42410598 G>A), RS1001645061 (17:42404232 A>G), RS1001833952 (17:42408679 C>T), RS1002201994 (17:42415965 G>A), RS1002254440 (17:42415636 G>A,C)

Disease associations

OMIM: gene MIM:603198 | disease phenotypes: MIM:613327, MIM:146840, MIM:147060, MIM:245590, MIM:608594

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital generalized lipodystrophy type 4	Strong	Autosomal recessive
Berardinelli-Seip congenital lipodystrophy	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
lipodystrophy	Definitive	AR

Mondo (6): congenital generalized lipodystrophy type 4 (MONDO:0013225), monogenic diabetes (MONDO:0015967), hyper-IgE recurrent infection syndrome 1, autosomal dominant (MONDO:0007818), growth hormone insensitivity with immune dysregulation 1, autosomal recessive (MONDO:0100211), congenital generalized lipodystrophy (MONDO:0006536), Berardinelli-Seip congenital lipodystrophy (MONDO:0018883)

Orphanet (4): Congenital generalized lipodystrophy type 4 (Orphanet:228429), Rare genetic diabetes mellitus (Orphanet:183625), Laron syndrome with immunodeficiency (Orphanet:220465), Autosomal dominant hyper-IgE syndrome due to STAT3 deficiency (Orphanet:2314)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000842	Hyperinsulinemia
HP:0000855	Insulin resistance
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000956	Acanthosis nigricans
HP:0001007	Hirsutism
HP:0001324	Muscle weakness
HP:0001371	Flexion contracture
HP:0001397	Hepatic steatosis
HP:0001508	Failure to thrive
HP:0001544	Prominent umbilicus
HP:0001649	Tachycardia
HP:0001657	Prolonged QT interval
HP:0001662	Bradycardia
HP:0001744	Splenomegaly
HP:0002015	Dysphagia
HP:0002019	Constipation
HP:0002021	Pyloric stenosis
HP:0002155	Hypertriglyceridemia
HP:0002240	Hepatomegaly
HP:0002595	Ileus
HP:0002617	Vascular dilatation
HP:0002650	Scoliosis
HP:0002719	Recurrent infections
HP:0002720	Decreased circulating IgA concentration
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003306	Spinal rigidity
HP:0003307	Hyperlordosis

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002874_17	Psoriasis	6.000000e-07
GCST004131_42	Inflammatory bowel disease	2.000000e-17
GCST004132_58	Crohn’s disease	2.000000e-11
GCST004133_53	Ulcerative colitis	1.000000e-10
GCST005527_33	Psoriasis	5.000000e-09
GCST011365_153	Myocardial infarction	3.000000e-06
GCST012229_195	Hip index	6.000000e-09
GCST90002395_256	Mean platelet volume	4.000000e-12
GCST90002401_547	Platelet distribution width	7.000000e-11
GCST90020025_1436	Waist-to-hip ratio adjusted for BMI	2.000000e-12
GCST90020027_458	Waist-hip index	5.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0007984	platelet component distribution width
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
C567925	Hyper-Ige Recurrent Infection Syndrome, Autosomal Dominant (supp.)
C564135	Immunodeficiency with Defective Leukocyte and Lymphocyte Function and with Response to Histamine-1 Antagonist (supp.)
C537871	Laron syndrome type 2 (supp.)
C567642	Lipodystrophy, Congenital Generalized, Type 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	3
Valproic Acid	affects expression, increases expression	3
sodium arsenite	affects binding, increases reaction, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Lipopolysaccharides	affects expression, affects response to substance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, increases abundance	2
Vitamin E	decreases reaction, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
titanium dioxide	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
cupric chloride	increases expression	1
coumarin	decreases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
polyhexamethyleneguanidine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_AW38	K562 eGFP-PTRF	Cancer cell line	Female
CVCL_B1MA	Abcam HeLa CAVIN1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00033982	PHASE3	COMPLETED	Posaconazole to Treat Invasive Fungal Infections
NCT06976658	PHASE2	RECRUITING	Glucokinase Activator in Monogenic Diabetes
NCT00527878	PHASE2	TERMINATED	Effect of Ranitidine on Hyper-IgE Recurrent Infection (Job’s) Syndrome
NCT02996448	PHASE2	TERMINATED	Safety, Tolerability, and Immunogenicity of One Dose of NDV 3A Vaccine in People With STAT3-Mutated Hyper-IgE Syndrome
NCT01795144	PHASE1	COMPLETED	Incretin Regulation of Insulin Secretion in Monogenic Diabetes
NCT00001515	PHASE1	COMPLETED	Diagnostic Effectiveness of Virtual Bronchoscopy
NCT00260702	PHASE1	COMPLETED	Omalizumab to Treat Hyper-IgE (Job’s) Syndrome
NCT04409795	PHASE2/PHASE3	COMPLETED	Oral Hypoglycemic Therapy for Monogenic Variant Carriers of the Joslin Medalist Study
NCT03988764	Not specified	RECRUITING	Monogenic Diabetes Misdiagnosed as Type 1
NCT05586594	Not specified	NOT_YET_RECRUITING	Identifying Maturity-onset Diabetes of the Young in Emirati Patients
NCT06478121	Not specified	RECRUITING	Understanding Beta Cell Disorders Through the Study of Rare Genotypes (ENDURE)
NCT06746610	Not specified	RECRUITING	Screening and Molecular Diagnosis-based Individualized Precision Management of Monogenic Diabetes
NCT07492004	Not specified	RECRUITING	China Monogenic Diabetes Registry
NCT07564518	Not specified	NOT_YET_RECRUITING	Application of FreeStyle Libre 2 for Evaluating Glycemic Variability Characteristics in Patients With Extreme Glucose Metabolism Phenotypes
NCT00005933	Not specified	COMPLETED	Learning and Behavior Problems in Children With Chronic Granulomatous Disease and Related Disorders
NCT00006150	Not specified	RECRUITING	Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome (HIES)
NCT02228941	Not specified	UNKNOWN	NFIL3-induced Pathological Enhancement of IgE Class Switch Recombination in Hyper-IgE Syndrome