VPS37C

Summary

VPS37C (VPS37C subunit of ESCRT-I, HGNC:26097) is a protein-coding gene on chromosome 11q12.2, encoding Vacuolar protein sorting-associated protein 37C (A5D8V6). Component of the ESCRT-I complex, a regulator of vesicular trafficking process.

VPS37C is a subunit of ESCRT-I (endosomal sorting complex required for transport I), a complex in the class E vacuolar protein sorting (VPS) pathway required for sorting ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies (Eastman et al., 2005 [PubMed 15509564]).

Source: NCBI Gene 55048 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 76 total
• MANE Select transcript: NM_017966

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26097
Approved symbol	VPS37C
Name	VPS37C subunit of ESCRT-I
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20847
Ensembl gene	ENSG00000167987
Ensembl biotype	protein_coding
OMIM	610038
Entrez	55048

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 2 retained_intron

ENST00000301765, ENST00000535818, ENST00000536000, ENST00000538036, ENST00000865209, ENST00000865210, ENST00000865211, ENST00000865212, ENST00000865213, ENST00000865214, ENST00000932806, ENST00000932807, ENST00000932808, ENST00000932809, ENST00000932810, ENST00000932811, ENST00000969167

RefSeq mRNA: 1 — MANE Select: NM_017966 NM_017966

CCDS: CCDS31573

Canonical transcript exons

ENST00000301765 — 5 exons

Exon	Start	End
ENSE00001119066	61133255	61133337
ENSE00001248522	61130257	61132539
ENSE00002323686	61161391	61161426
ENSE00003510659	61134036	61134207
ENSE00003594793	61138737	61138835

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.8642 / max 297.4962, expressed in 1799 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119955	5.9401	1726
119954	5.8307	1722
119953	0.0934	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.27	gold quality
amniotic fluid	UBERON:0000173	97.81	gold quality
endothelial cell	CL:0000115	97.51	gold quality
palpebral conjunctiva	UBERON:0001812	97.21	gold quality
esophagus squamous epithelium	UBERON:0006920	96.95	gold quality
oocyte	CL:0000023	96.54	gold quality
visceral pleura	UBERON:0002401	96.54	gold quality
type B pancreatic cell	CL:0000169	96.47	gold quality
epithelium of esophagus	UBERON:0001976	96.13	gold quality
squamous epithelium	UBERON:0006914	95.77	gold quality
parotid gland	UBERON:0001831	95.40	gold quality
eye	UBERON:0000970	95.38	gold quality
parietal pleura	UBERON:0002400	95.04	gold quality
pleura	UBERON:0000977	94.96	gold quality
cardia of stomach	UBERON:0001162	94.87	gold quality
sperm	CL:0000019	94.67	gold quality
epithelium of nasopharynx	UBERON:0001951	94.65	gold quality
gingival epithelium	UBERON:0001949	94.44	gold quality
pylorus	UBERON:0001166	94.42	gold quality
skin of hip	UBERON:0001554	94.40	gold quality
male germ cell	CL:0000015	94.26	gold quality
germinal epithelium of ovary	UBERON:0001304	94.26	gold quality
tongue squamous epithelium	UBERON:0006919	94.05	gold quality
bronchial epithelial cell	CL:0002328	93.94	gold quality
epithelium of bronchus	UBERON:0002031	93.71	gold quality
epithelial cell of pancreas	CL:0000083	93.67	gold quality
upper leg skin	UBERON:0004262	93.62	gold quality
nasal cavity epithelium	UBERON:0005384	93.61	gold quality
bronchus	UBERON:0002185	93.58	gold quality
cervix squamous epithelium	UBERON:0006922	93.55	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

92 targeting VPS37C, 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-4283	100.00	66.42	2097
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6785-5P	99.82	68.68	4428

Literature-anchored findings (GeneRIF, showing 3)

• VPS37C as a functional component of mammalian endosomal sorting complex required for transport-I (PMID:15509564)
• VPS37B and appeared to interact with ALG-2 in a stronger manner than TSG101 does (PMID:23924735)
• VPS37C facilitates erythroid differentiation by promoting EKLF stability. (PMID:37307706)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	vps37c	ENSDARG00000031836
mus_musculus	Vps37c	ENSMUSG00000048832
rattus_norvegicus	Vps37c	ENSRNOG00000046439
drosophila_melanogaster	Vps37B	FBGN0037299

Paralogs (3): VPS37B (ENSG00000139722), VPS37A (ENSG00000155975), VPS37D (ENSG00000176428)

Protein

Protein identifiers

Vacuolar protein sorting-associated protein 37C — A5D8V6 (reviewed: A5D8V6)

Alternative names: ESCRT-I complex subunit VPS37C

All UniProt accessions (2): A5D8V6, F5H4Q5

UniProt curated annotations — full annotation on UniProt →

Function. Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in cell growth and differentiation.

Subunit / interactions. Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoichiometry. Interacts with TSG101, VPS28, MVB12A and MVB12B. Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and UBAP1 in a 1:1:1:1 stoichiometry. Interacts with HGS and STAM2. Interacts with CEP55.

Subcellular location. Late endosome membrane.

Post-translational modifications. Phosphorylated by TBK1.

Similarity. Belongs to the VPS37 family.

RefSeq proteins (1): NP_060436* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009851	Mod_r	Domain
IPR029012	Helix_hairpin_bin_sf	Homologous_superfamily
IPR037202	ESCRT_assembly_dom	Homologous_superfamily

Pfam: PF07200

UniProt features (10 total): compositionally biased region 4, sequence variant 2, chain 1, domain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A5D8V6-F1	68.94	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 (1): 29

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-162588	Budding and maturation of HIV virion
R-HSA-174490	Membrane binding and targetting of GAG proteins
R-HSA-917729	Endosomal Sorting Complex Required For Transport (ESCRT)
R-HSA-9610379	HCMV Late Events
R-HSA-9615710	Late endosomal microautophagy

MSigDB gene sets: 203 (showing top): REACTOME_ENDOSOMAL_SORTING_COMPLEX_REQUIRED_FOR_TRANSPORT_ESCRT, GOBP_ENDOSOME_ORGANIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_ORGANIZATION, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MACROAUTOPHAGY, GTGCCTT_MIR506, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, REACTOME_HIV_INFECTION, GOBP_PROTEIN_LOCALIZATION_TO_VACUOLE

GO Biological Process (9): protein targeting to membrane (GO:0006612), protein targeting to vacuole (GO:0006623), macroautophagy (GO:0016236), multivesicular body assembly (GO:0036258), viral budding via host ESCRT complex (GO:0039702), ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway (GO:0043162), protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway (GO:0043328), membrane fission (GO:0090148), protein transport (GO:0015031)

GO Molecular Function (2): calcium-dependent protein binding (GO:0048306), protein binding (GO:0005515)

GO Cellular Component (9): ESCRT I complex (GO:0000813), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), cilium (GO:0005929), endosome membrane (GO:0010008), late endosome membrane (GO:0031902), extracellular exosome (GO:0070062), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Late Phase of HIV Life Cycle	1
Synthesis And Processing Of GAG, GAGPOL Polyproteins	1
Membrane Trafficking	1
HCMV Infection	1
Autophagy	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein targeting	2
intracellular protein transport	2
protein localization to vacuole	2
establishment of protein localization to vacuole	2
endosome membrane	2
cellular anatomical structure	2
endomembrane system	2
establishment of protein localization to membrane	1
vacuolar transport	1
autophagosome assembly	1
autophagy	1
multivesicular body organization	1
organelle assembly	1
viral budding	1
ubiquitin-dependent protein catabolic process	1
protein catabolic process in the vacuole	1
multivesicular body sorting pathway	1
late endosome to vacuole transport via multivesicular body sorting pathway	1
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	1
membrane organization	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
calcium ion binding	1
protein binding	1
binding	1
ESCRT complex	1
membrane protein complex	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
late endosome	1
extracellular vesicle	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

714 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VPS37C	VPS28	Q9UK41	969
VPS37C	TSG101	Q99816	921
VPS37C	VPS4A	Q9UN37	839
VPS37C	VPS36	Q86VN1	740
VPS37C	MVB12A	Q96EY5	728
VPS37C	SNF8	Q96H20	696
VPS37C	UBAP1	Q9NZ09	664
VPS37C	MVB12B	Q9H7P6	646
VPS37C	VPS25	Q9BRG1	584
VPS37C	ABCC3	O15438	583
VPS37C	CHMP2A	O43633	567
VPS37C	VPS4B	O75351	560
VPS37C	CHMP4C	Q96CF2	534
VPS37C	CHMP6	Q96FZ7	525
VPS37C	TOM1L1	O75674	462

IntAct

385 interactions, top by confidence:

A	B	Type	Score
CEP55	VPS37C	psi-mi:“MI:0915”(physical association)	0.800
VPS37C	CEP55	psi-mi:“MI:0915”(physical association)	0.800
VPS37C	XIAP	psi-mi:“MI:0915”(physical association)	0.780
TSG101	VPS37C	psi-mi:“MI:0915”(physical association)	0.780
XIAP	VPS37C	psi-mi:“MI:0915”(physical association)	0.780
VPS37C	TSG101	psi-mi:“MI:0915”(physical association)	0.780
VPS37C	WWP2	psi-mi:“MI:0915”(physical association)	0.720
VPS37C	SORBS3	psi-mi:“MI:0915”(physical association)	0.720
PDCD6	VPS37C	psi-mi:“MI:0915”(physical association)	0.720
VPS37C	STAM2	psi-mi:“MI:0915”(physical association)	0.720
VPS37C	DAZAP2	psi-mi:“MI:0915”(physical association)	0.720
VPS37C	C1orf94	psi-mi:“MI:0915”(physical association)	0.720
MAPK1IP1L	VPS37C	psi-mi:“MI:0915”(physical association)	0.720
TFG	VPS37C	psi-mi:“MI:0915”(physical association)	0.720
STAM2	VPS37C	psi-mi:“MI:0915”(physical association)	0.720
VPS37C	MAPK1IP1L	psi-mi:“MI:0915”(physical association)	0.720
VPS37C	PDCD6	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (172): VPS37C (Two-hybrid), VPS37C (Two-hybrid), VPS37C (Two-hybrid), VPS37C (Two-hybrid), VPS37C (Two-hybrid), VPS37C (Two-hybrid), VPS37C (Two-hybrid), VPS37C (Two-hybrid), VPS37C (Two-hybrid), VPS37C (Two-hybrid), VPS37C (Two-hybrid), VPS37C (Two-hybrid), VPS37C (Two-hybrid), VPS37C (Two-hybrid), VPS37C (Two-hybrid)

ESM2 similar proteins: A0JPN4, A2A9T0, A5D8V6, A6ND36, A6QQJ8, A7MCY6, E9Q2Z1, O14529, O54714, O70260, O88902, P70298, P98175, Q07912, Q0IIJ3, Q13227, Q13625, Q148V8, Q15025, Q15942, Q3SZL6, Q3U564, Q3UIL6, Q499E4, Q5BJU7, Q5D1E7, Q5D1E8, Q5NVG8, Q5R9T2, Q5RBV9, Q5U2X5, Q5XIA0, Q61140, Q62415, Q62523, Q63767, Q6DG50, Q6IQ23, Q810I0, Q8CG79

Diamond homologs: A5D8V6, Q5R9T2, Q810I0, Q86XT2, Q8R0J7, Q8R105, Q9H9H4, Q9SCP9, Q8NEZ2, Q3EBL9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TBK1	“down-regulates activity”	VPS37C	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1536 predictions. Top by Δscore:

Variant	Effect	Δscore
11:61132424:T:TA	donor_gain	1.0000
11:61132536:TGGC:T	acceptor_gain	1.0000
11:61132538:GCCTG:G	acceptor_loss	1.0000
11:61132539:CCTGG:C	acceptor_loss	1.0000
11:61132540:C:CC	acceptor_gain	1.0000
11:61132540:CTGGA:C	acceptor_loss	1.0000
11:61132541:T:A	acceptor_loss	1.0000
11:61132549:A:C	acceptor_gain	1.0000
11:61134032:CTACC:C	donor_loss	1.0000
11:61134033:TA:T	donor_loss	1.0000
11:61134034:A:AC	donor_gain	1.0000
11:61134034:AC:A	donor_gain	1.0000
11:61134035:C:CC	donor_gain	1.0000
11:61134035:CC:C	donor_gain	1.0000
11:61134035:CCCAG:C	donor_gain	1.0000
11:61134039:G:C	donor_gain	1.0000
11:61134075:T:TA	donor_gain	1.0000
11:61134205:GACC:G	acceptor_loss	1.0000
11:61134208:C:CC	acceptor_gain	1.0000
11:61132535:ATGGC:A	acceptor_gain	0.9900
11:61132537:GGC:G	acceptor_gain	0.9900
11:61132538:GC:G	acceptor_gain	0.9900
11:61132539:CC:C	acceptor_gain	0.9900
11:61132548:C:CT	acceptor_gain	0.9900
11:61133249:TCTCA:T	donor_loss	0.9900
11:61133250:CTCA:C	donor_loss	0.9900
11:61133251:TCAC:T	donor_loss	0.9900
11:61133252:CACC:C	donor_loss	0.9900
11:61133253:A:C	donor_loss	0.9900
11:61133254:CCTC:C	donor_loss	0.9900

AlphaMissense

2244 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:61132492:G:C	F132L	0.999
11:61132492:G:T	F132L	0.999
11:61132494:A:G	F132L	0.999
11:61134161:C:G	R47P	0.999
11:61132493:A:G	F132S	0.998
11:61132523:A:G	F122S	0.998
11:61133260:A:G	S115P	0.998
11:61134080:A:G	L74P	0.998
11:61134177:C:G	A42P	0.998
11:61132448:C:G	R147P	0.997
11:61132468:C:A	R140S	0.997
11:61132468:C:G	R140S	0.997
11:61134101:A:G	L67P	0.997
11:61134153:C:G	A50P	0.997
11:61134185:C:G	R39P	0.997
11:61132451:C:G	R146P	0.996
11:61132458:G:C	H144D	0.996
11:61134155:A:G	L49P	0.996
11:61132533:C:G	A119P	0.995
11:61134171:C:G	A44P	0.995
11:61138795:A:G	L12P	0.995
11:61132430:A:G	L153P	0.994
11:61132480:A:C	F136L	0.994
11:61132480:A:T	F136L	0.994
11:61132482:A:G	F136L	0.994
11:61134163:G:C	N46K	0.994
11:61134163:G:T	N46K	0.994
11:61134173:A:G	L43P	0.994
11:61132457:T:G	H144P	0.993
11:61132493:A:C	F132C	0.993

dbSNP variants (sampled 300 via entrez): RS1000005211 (11:61153116 C>G,T), RS1000221270 (11:61146826 A>G), RS1000243183 (11:61137305 T>C), RS1000314390 (11:61137035 A>G), RS1000503490 (11:61130175 G>A), RS1000524699 (11:61152795 A>C,G), RS1000697099 (11:61135862 GC>G), RS1000793423 (11:61141475 G>C), RS1000971805 (11:61157581 C>T), RS1001131571 (11:61151410 T>C), RS1001351229 (11:61131317 CCT>C), RS1001385559 (11:61130968 T>TCGCC), RS1001417203 (11:61151702 C>T), RS1001676141 (11:61139583 G>A), RS1001832236 (11:61146757 C>T)

Disease associations

OMIM: gene MIM:610038 | 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
GCST005569_21	Rheumatoid arthritis	3.000000e-08
GCST010726_46	Periventricular white matter hyperintensities	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005665	white matter hyperintensity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression	2
Tretinoin	affects cotreatment, increases expression	2
Cyclosporine	increases expression	2
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
sodium arsenite	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Diethylhexyl Phthalate	increases abundance, decreases methylation	1
Doxorubicin	decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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