CHMP3

Summary

CHMP3 (charged multivesicular body protein 3, HGNC:29865) is a protein-coding gene on chromosome 2p11.2, encoding Charged multivesicular body protein 3 (Q9Y3E7). Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. It is a selective cancer dependency (DepMap: 80.1% of cell lines).

This gene encodes a protein that sorts transmembrane proteins into lysosomes/vacuoles via the multivesicular body (MVB) pathway. This protein, along with other soluble coiled-coil containing proteins, forms part of the ESCRT-III protein complex that binds to the endosomal membrane and recruits additional cofactors for protein sorting into the MVB. This protein may also co-immunoprecipitate with a member of the IFG-binding protein superfamily. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream ring finger protein 103 (RNF103) gene.

Source: NCBI Gene 51652 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 15 total
• Cancer dependency (DepMap): dependent in 80.1% of screened cell lines
• MANE Select transcript: NM_016079

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29865
Approved symbol	CHMP3
Name	charged multivesicular body protein 3
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Aliases	NEDF, CGI-149
Ensembl gene	ENSG00000115561
Ensembl biotype	protein_coding
OMIM	610052
Entrez	51652

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000263856, ENST00000393773, ENST00000409225, ENST00000409727, ENST00000409810, ENST00000466032, ENST00000485465, ENST00000486404, ENST00000494623, ENST00000953402, ENST00000953403, ENST00000953404

RefSeq mRNA: 3 — MANE Select: NM_016079 NM_001005753, NM_001193517, NM_016079

CCDS: CCDS33236, CCDS42707, CCDS54375

Canonical transcript exons

ENST00000263856 — 6 exons

Exon	Start	End
ENSE00001588077	86503430	86505949
ENSE00001861633	86563304	86563443
ENSE00003509231	86542252	86542312
ENSE00003539088	86507479	86507593
ENSE00003633869	86510358	86510479
ENSE00003675740	86529218	86529397

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 44.0784 / max 602.8518, expressed in 1813 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29549	32.8366	1803
29548	8.1448	1693
29551	1.9305	964
29550	0.9336	527
29547	0.2240	78
29546	0.0049	3
29544	0.0040	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.42	gold quality
secondary oocyte	CL:0000655	99.06	gold quality
cerebellar vermis	UBERON:0004720	99.01	gold quality
nipple	UBERON:0002030	98.95	gold quality
skin of hip	UBERON:0001554	98.46	gold quality
urethra	UBERON:0000057	98.24	gold quality
saphenous vein	UBERON:0007318	98.19	gold quality
parotid gland	UBERON:0001831	98.17	gold quality
rectum	UBERON:0001052	98.04	gold quality
trabecular bone tissue	UBERON:0002483	98.02	gold quality
heart right ventricle	UBERON:0002080	97.99	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.97	gold quality
upper leg skin	UBERON:0004262	97.93	gold quality
mammalian vulva	UBERON:0000997	97.88	gold quality
colonic epithelium	UBERON:0000397	97.79	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.69	gold quality
synovial joint	UBERON:0002217	97.68	gold quality
lower esophagus	UBERON:0013473	97.68	gold quality
penis	UBERON:0000989	97.65	gold quality
urinary bladder	UBERON:0001255	97.48	gold quality
oocyte	CL:0000023	97.41	gold quality
pons	UBERON:0000988	97.39	gold quality
vena cava	UBERON:0004087	97.39	gold quality
trachea	UBERON:0003126	97.36	gold quality
colonic mucosa	UBERON:0000317	97.27	gold quality
gall bladder	UBERON:0002110	97.22	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.22	gold quality
islet of Langerhans	UBERON:0000006	97.20	gold quality
popliteal artery	UBERON:0002250	97.18	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	17.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

89 targeting CHMP3, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-577	99.78	69.13	2479

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 80.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 16)

• In rodents, this protein selectively binds phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 3,4-bisphosphate and may participate in endosomal trafficking. (PMID:12878588)
• data suggest that mac25/IGFBP-rP1 and 25.1 (NEDF) may play a functional role in the NE differentiation of NSCLC cell lines and may provide a novel therapeutic target for treating lung cancers, in particular NSCLC with NE differentiation (PMID:16302002)
• ESCRT subunit is important for degradation of the epidermal growth factor receptor (EGFR) and for transport of the receptor from endosomes to lysosomes. (PMID:16554368)
• CHMP proteins are regulated through an autoinhibitory switch mechanism that allows tight control of endosomal sorting complex ESCRT-III assembly (PMID:17146056)
• A dominant-negative version of CHMP3, which specifically prevents targeting of AMSH (STAMBP) to endosomes, inhibits degradation but not internalization of epidermal growth factor receptor. (PMID:17261583)
• Data demonstrate that the VPS24 gene gives rise to two functionally distinct proteins, one of which is involved in the ESCRT pathway and another novel protein that serves an anti-apoptotic role. (PMID:17331679)
• expression of dominant negative forms of Vps4 and Vps24, two components of the MVB pathway, rresult in an impairment in infectious herpes simplex virus assembly/egress (PMID:17686835)
• UBPY MIT domain and another ubiquitin isopeptidase, AMSH, reveals common interactions with CHMP1A and CHMP1B but a distinct selectivity of AMSH for CHMP3/VPS24, a core subunit of the ESCRT-III complex, and UBPY for CHMP7. (PMID:17711858)
• study found the ESCRT-III proteins CHMP2A & CHMP3 could assemble in vitro into helical tubular structures that expose their membrane interaction sites on the outside of the tubule; VPS4 could bind on the inside of the tubule & disassemble the tubes (PMID:18687924)
• Data show that the N-terminal core domains of increased sodium tolerance-1 (IST1) and charged multivesicular body protein-3 (CHMP3) form equivalent four-helix bundles, revealing that IST1 is a previously unrecognized ESCRT-III family member. (PMID:19525971)
• tight coupling of ESCRT-III CHMP3 and AMSH functions and provide insight into the regulation of ESCRT-III (PMID:21827950)
• Protein kinase CK2 alpha is involved in the phosphorylation of the ESCRT-III subunits CHMP3 and CHMP2B, as well as of VPS4B/SKD1, an ATPase that mediates ESCRT-III disassembly. (PMID:24440309)
• miR-122-5p promotes aggression and epithelial-mesenchymal transition in triple-negative breast cancer by suppressing charged multivesicular body protein 3 through mitogen-activated protein kinase signaling. (PMID:31541468)
• RetroCHMP3 blocks budding of enveloped viruses without blocking cytokinesis. (PMID:34597582)
• A homozygous variant in CHMP3 is associated with complex hereditary spastic paraplegia. (PMID:35710109)
• CHMP3 promotes the progression of hepatocellular carcinoma by inhibiting caspase-1-dependent pyroptosis. (PMID:38038147)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	chmp3	ENSDARG00000038064
mus_musculus	Chmp3	ENSMUSG00000053119
rattus_norvegicus	Chmp3	ENSRNOG00000007356
drosophila_melanogaster	Vps24	FBGN0037231
caenorhabditis_elegans		WBGENE00020866

Paralogs (4): CHMP2B (ENSG00000083937), CHMP2A (ENSG00000130724), CHMP1A (ENSG00000131165), CHMP1B (ENSG00000255112)

Protein

Protein identifiers

Charged multivesicular body protein 3 — Q9Y3E7 (reviewed: Q9Y3E7)

Alternative names: Chromatin-modifying protein 3, Neuroendocrine differentiation factor, Vacuolar protein sorting-associated protein 24

All UniProt accessions (1): Q9Y3E7

UniProt curated annotations — full annotation on UniProt →

Function. Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Selectively binds to phosphatidylinositol 3,5-bisphosphate PtdIns(3,5)P2 and PtdIns(3,4)P2 in preference to other phosphoinositides tested. Involved in late stages of cytokinesis. Plays a role in endosomal sorting/trafficking of EGF receptor. Isoform 2 prevents stress-mediated cell death and accumulation of reactive oxygen species when expressed in yeast cells.

Subunit / interactions. Probable core component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome. Several assembly forms of ESCRT-III may exist that interact and act sequentially. Forms a metastable monomer in solution; its core structure (without part of the putative autoinhibitory C-terminal acidic region) oligomerizes into a flat lattice via two different dimerization interfaces. In vitro, heteromerizes with CHMP2A (but not CHMP4) to form helical tubular structures that expose membrane-interacting sites on the outside whereas VPS4B can associate on the inside of the tubule. May interact with IGFBP7; the relevance of such interaction however remains unclear. Interacts with CHMP2A. Interacts with CHMP4A; the interaction requires the release of CHMP4A autoinhibition. Interacts with VPS4A. Interacts with STAMBP; the interaction appears to relieve the autoinhibition of CHMP3. Interacts with VTA1.

Subcellular location. Cytoplasm. Cytosol. Membrane. Endosome. Late endosome membrane.

Tissue specificity. Widely expressed. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Domain organisation. The acidic C-terminus and the basic N-termminus are thought to render the protein in a closed, soluble and inactive conformation through an autoinhibitory intramolecular interaction. The open and active conformation, which enables membrane binding and oligomerization, is achieved by interaction with other cellular binding partners, probably including other ESCRT components.

Miscellaneous. Its overexpression strongly inhibits HIV-1 release.

Similarity. Belongs to the SNF7 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9Y3E7-1	1, Vps24alpha	yes
Q9Y3E7-2	2, Vps24beta
Q9Y3E7-3	3
Q9Y3E7-4	4

RefSeq proteins (3): NP_001005753, NP_001180446, NP_057163* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005024	Snf7_fam	Family

Pfam: PF03357

UniProt features (49 total): mutagenesis site 16, region of interest 8, helix 6, splice variant 3, strand 3, coiled-coil region 2, site 2, initiator methionine 1, chain 1, short sequence motif 1, compositionally biased region 1, modified residue 1, lipid moiety-binding region 1, cross-link 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
2XZE	X-RAY DIFFRACTION	1.75
2GD5	X-RAY DIFFRACTION	2.8
7ZCG	ELECTRON MICROSCOPY	3.3
7ZCH	ELECTRON MICROSCOPY	3.6
3FRV	X-RAY DIFFRACTION	3.7
3FRT	X-RAY DIFFRACTION	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y3E7-F1	81.94	0.58

Functional residue map

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

Catalytic / active sites (2): 48 (important for autoinhibitory function); 216 (interaction with stambp)

Post-translational modifications (3): 200, 2, 179

Mutagenesis-validated functional residues (16):

Position	Phenotype
24–25	impairs hiv-1 release; when associated with s-28.
28	impairs hiv-1 release; when associated with 24-s-a-25.
48	induces assembly with chmp2a into helical tubes in vitro; when associated with d-64. enhances inhibition of hiv-1 buddin
54	abolishes dimerization; when associated with n-56; e-59 and 62-d-e-63.
56	abolishes dimerization; when associated with s-54; e-59 and 62-d-e-63.
59	abolishes interaction with chmp2a and assembly into helical tubes in vitro; when associated with d-62; d-168 and d-169.
59	abolishes dimerization; when associated with s-54; n-56 and 62-d-e-63.
62–63	abolishes dimerization; when associated with s-54; n-56 and e-59.
62	abolishes interaction with chmp2a and assembly into helical tubes in vitro; when associated with d-59; d-168 and d-169.
64	induces assembly with chmp2a into helical tubes in vitro; when associated with d-48.
78–79	abolishes dimerization.
168–169	induces assembly with chmp2a into helical tubes in vitro and slightly enhances inhibition of hiv-1 budding in vivo. abol
179–222	membrane association; releases autoinhibition.
216–217	abolishes interaction with vps4a and stambp.
221–222	abolishes interaction with vps4a and stambp.
222	impairs interaction with vps4a and stambp.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-162588	Budding and maturation of HIV virion
R-HSA-1632852	Macroautophagy
R-HSA-5620971	Pyroptosis
R-HSA-917729	Endosomal Sorting Complex Required For Transport (ESCRT)
R-HSA-9610379	HCMV Late Events
R-HSA-9615710	Late endosomal microautophagy
R-HSA-9668328	Sealing of the nuclear envelope (NE) by ESCRT-III
R-HSA-9679504	Translation of Replicase and Assembly of the Replication Transcription Complex
R-HSA-9694676	Translation of Replicase and Assembly of the Replication Transcription Complex

MSigDB gene sets: 307 (showing top): GOBP_MITOTIC_CYTOKINESIS, REACTOME_ENDOSOMAL_SORTING_COMPLEX_REQUIRED_FOR_TRANSPORT_ESCRT, GOBP_CHROMOSOME_ORGANIZATION, GOBP_NUCLEAR_MEMBRANE_REASSEMBLY, GOBP_LYSOSOMAL_TRANSPORT, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_ENDOSOME_ORGANIZATION, GOBP_VACUOLE_ORGANIZATION, GOBP_VESICLE_LOCALIZATION, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_MEMBRANE_BIOGENESIS, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, GOBP_CHROMOSOME_LOCALIZATION, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT

GO Biological Process (32): plasma membrane repair (GO:0001778), autophagy (GO:0006914), apoptotic process (GO:0006915), nucleus organization (GO:0006997), mitotic metaphase chromosome alignment (GO:0007080), regulation of centrosome duplication (GO:0010824), protein transport (GO:0015031), macroautophagy (GO:0016236), viral release from host cell (GO:0019076), nuclear membrane reassembly (GO:0031468), positive regulation of cytokinesis (GO:0032467), endosome transport via multivesicular body sorting pathway (GO:0032509), 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), suppression of viral release by host (GO:0044790), late endosome to vacuole transport (GO:0045324), viral budding from plasma membrane (GO:0046761), regulation of endosome size (GO:0051036), protein polymerization (GO:0051258), vesicle fusion with vacuole (GO:0051469), multivesicular body-lysosome fusion (GO:0061763), midbody abscission (GO:0061952), multivesicular body sorting pathway (GO:0071985), membrane fission (GO:0090148), autophagosome maturation (GO:0097352), regulation of mitotic spindle assembly (GO:1901673), late endosome to lysosome transport (GO:1902774), regulation of early endosome to late endosome transport (GO:2000641), vacuolar transport (GO:0007034), endosome to lysosome transport (GO:0008333), cell division (GO:0051301)

GO Molecular Function (6): phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), phosphatidylcholine binding (GO:0031210), identical protein binding (GO:0042802), molecular function inhibitor activity (GO:0140678), ubiquitin-specific protease binding (GO:1990381), protein binding (GO:0005515)

GO Cellular Component (20): autophagosome membrane (GO:0000421), kinetochore (GO:0000776), ESCRT III complex (GO:0000815), nuclear pore (GO:0005643), lysosomal membrane (GO:0005765), early endosome (GO:0005769), late endosome (GO:0005770), multivesicular body (GO:0005771), kinetochore microtubule (GO:0005828), cytosol (GO:0005829), plasma membrane (GO:0005886), midbody (GO:0030496), cytoplasmic vesicle (GO:0031410), multivesicular body membrane (GO:0032585), extracellular exosome (GO:0070062), amphisome membrane (GO:1904930), cytoplasm (GO:0005737), endosome (GO:0005768), membrane (GO:0016020), late endosome membrane (GO:0031902)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Autophagy	2
Late Phase of HIV Life Cycle	1
Regulated Necrosis	1
Membrane Trafficking	1
HCMV Infection	1
Nuclear Envelope (NE) Reassembly	1
SARS-CoV-1 Infection	1
Early SARS-CoV-2 Infection Events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
multivesicular body sorting pathway	2
viral budding	2
endosome membrane	2
endosome	2
late endosome	2
cytoplasm	2
plasma membrane organization	1
wound healing	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
organelle organization	1
mitotic sister chromatid segregation	1
mitotic cell cycle	1
metaphase chromosome alignment	1
mitotic cell cycle process	1
regulation of centrosome cycle	1
centrosome duplication	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
autophagosome assembly	1
autophagy	1
viral process	1
viral life cycle	1
exit from host cell	1
membrane assembly	1
nuclear membrane organization	1
cytokinesis	1
regulation of cytokinesis	1
positive regulation of cell division	1
positive regulation of cell cycle process	1
endosomal transport	1
multivesicular body organization	1
organelle assembly	1
ubiquitin-dependent protein catabolic process	1

Protein interactions and networks

STRING

926 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHMP3	CHMP6	Q96FZ7	999
CHMP3	CHMP4A	Q9BY43	999
CHMP3	CHMP1A	Q9HD42	995
CHMP3	CHMP2A	O43633	991
CHMP3	CHMP5	Q9NZZ3	989
CHMP3	STAMBP	O95630	974
CHMP3	IST1	P53990	970
CHMP3	CHMP1B	Q7LBR1	963
CHMP3	VPS4A	Q9UN37	949
CHMP3	VPS4B	O75351	940
CHMP3	VPS25	Q9BRG1	933
CHMP3	VPS36	Q86VN1	904
CHMP3	CHMP4C	Q96CF2	898
CHMP3	CHMP2B	Q9UQN3	887
CHMP3	TSG101	Q99816	883

IntAct

122 interactions, top by confidence:

A	B	Type	Score
STAMBP	CHMP3	psi-mi:“MI:0915”(physical association)	0.960
CHMP3	STAMBP	psi-mi:“MI:0915”(physical association)	0.960
CHMP3	STAMBP	psi-mi:“MI:0403”(colocalization)	0.960
CHMP3	STAMBP	psi-mi:“MI:2364”(proximity)	0.960
STAMBP	PIK3C2A	psi-mi:“MI:0914”(association)	0.730
CHMP4B	CHMP3	psi-mi:“MI:0407”(direct interaction)	0.690
CHMP3	CHMP4B	psi-mi:“MI:0915”(physical association)	0.690
CHMP4B	CHMP3	psi-mi:“MI:0915”(physical association)	0.690
CHMP3	CHMP2A	psi-mi:“MI:0570”(protein cleavage)	0.670
CHMP2A	CHMP3	psi-mi:“MI:0407”(direct interaction)	0.670
CHMP2A	CHMP3	psi-mi:“MI:0915”(physical association)	0.670
CHMP2B	CHMP3	psi-mi:“MI:0407”(direct interaction)	0.590

BioGRID (121): CHMP3 (Two-hybrid), CHMP3 (Affinity Capture-MS), CHMP3 (Affinity Capture-MS), CHMP3 (Affinity Capture-MS), CHMP3 (Affinity Capture-MS), STAMBP (Reconstituted Complex), CHMP1B (Co-fractionation), CHMP1B (Co-fractionation), CHMP4B (Co-fractionation), CHMP4B (Co-fractionation), CHMP3 (Affinity Capture-MS), CHMP3 (Affinity Capture-MS), CHMP3 (Affinity Capture-MS), CHMP3 (Affinity Capture-MS), CHMP3 (Affinity Capture-MS)

ESM2 similar proteins: A2VDY3, O14177, O43633, O74422, P0C0A3, P0C149, P0CR54, P0CR55, P36108, P59074, Q4R574, Q503V0, Q54JK4, Q569C1, Q58CS7, Q5ABD0, Q5B5E0, Q5BKM3, Q5R861, Q5RAU5, Q5ZHN1, Q5ZL55, Q6BSH2, Q6CBS3, Q6DFS6, Q6GMA4, Q6GNN8, Q6IP52, Q6NRM7, Q6NU11, Q6NY88, Q753W3, Q7ZW25, Q86H98, Q871Y8, Q8CGS4, Q8GXN6, Q8T0Q4, Q96CF2, Q96FZ7

Diamond homologs: O14296, P36095, Q4R574, Q58CS7, Q5BKM3, Q5RAU5, Q6NRM7, Q6NY88, Q8CGS4, Q9CQ10, Q9LXH5, Q9Y3E7, Q54P63, Q9FFB3, Q3SX42, Q5RAV2, Q5ZHN1, Q66IV6, Q6NVL7, Q7SYR0, Q8BJF9, Q941D5, Q9UQN3, Q9SKI2, O43633, Q0WTY4, Q54DB1, Q5F3A2, Q6DFS6, Q6IP52, Q6NXD2, Q7ZW25, Q9DB34

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CHMP3	up-regulates	Viral_budding
VPS4A	“up-regulates activity”	CHMP3	cleavage
CHMP3	“form complex”	ESCRT-III	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 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
Budding and maturation of HIV virion	7	46.0×	5e-08
Endosomal Sorting Complex Required For Transport (ESCRT)	7	41.6×	5e-08
Late endosomal microautophagy	5	26.3×	1e-04
HCMV Late Events	7	11.1×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
nuclear membrane reassembly	5	55.7×	2e-06
late endosome to lysosome transport	5	55.7×	2e-06
viral budding via host ESCRT complex	6	54.1×	2e-07
multivesicular body sorting pathway	6	54.1×	2e-07
multivesicular body assembly	8	47.3×	3e-09
midbody abscission	5	41.2×	6e-06
regulation of mitotic spindle assembly	5	41.2×	6e-06
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	6	36.6×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1086 predictions. Top by Δscore:

Variant	Effect	Δscore
2:86505945:GGCCC:G	acceptor_gain	1.0000
2:86505946:GCCC:G	acceptor_gain	1.0000
2:86505947:CCC:C	acceptor_gain	1.0000
2:86505947:CCCC:C	acceptor_gain	1.0000
2:86505948:CC:C	acceptor_gain	1.0000
2:86505948:CCC:C	acceptor_gain	1.0000
2:86505949:CC:C	acceptor_gain	1.0000
2:86505950:C:A	acceptor_loss	1.0000
2:86505950:C:CC	acceptor_gain	1.0000
2:86505950:C:T	acceptor_gain	1.0000
2:86505950:CT:C	acceptor_loss	1.0000
2:86507474:CATA:C	donor_loss	1.0000
2:86507475:ATAC:A	donor_loss	1.0000
2:86507476:TAC:T	donor_loss	1.0000
2:86507476:TACCT:T	donor_loss	1.0000
2:86507477:A:T	donor_loss	1.0000
2:86507478:C:A	donor_loss	1.0000
2:86507478:CCTG:C	donor_gain	1.0000
2:86507526:T:TA	donor_gain	1.0000
2:86507589:CCAGC:C	acceptor_gain	1.0000
2:86507590:CAGC:C	acceptor_gain	1.0000
2:86507590:CAGCC:C	acceptor_gain	1.0000
2:86507592:GC:G	acceptor_gain	1.0000
2:86507593:CC:C	acceptor_gain	1.0000
2:86507593:CCTAA:C	acceptor_loss	1.0000
2:86507594:C:CC	acceptor_gain	1.0000
2:86507594:CTAA:C	acceptor_loss	1.0000
2:86507595:T:A	acceptor_loss	1.0000
2:86510354:TCA:T	donor_loss	1.0000
2:86510355:CAC:C	donor_loss	1.0000

AlphaMissense

1483 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:86507590:C:A	G138W	0.999
2:86507593:C:G	A137P	0.999
2:86510445:G:C	S107R	0.999
2:86510445:G:T	S107R	0.999
2:86510447:T:G	S107R	0.999
2:86529248:A:G	S86P	0.999
2:86529296:A:G	S70P	0.999
2:86529313:G:T	A64D	0.999
2:86529353:C:G	A51P	0.999
2:86510375:A:G	S131P	0.998
2:86510416:A:G	L117P	0.998
2:86510429:C:G	A113P	0.998
2:86510465:C:G	A101P	0.998
2:86529218:C:G	A96P	0.998
2:86529260:C:G	A82P	0.998
2:86529266:A:G	S80P	0.998
2:86529274:A:G	L77P	0.998
2:86529287:C:G	A73P	0.998
2:86529314:C:G	A64P	0.998
2:86529324:G:C	C60W	0.998
2:86507496:A:G	L169P	0.997
2:86507586:A:C	I139S	0.997
2:86507586:A:G	I139T	0.997
2:86507589:C:A	G138V	0.997
2:86529316:A:G	L63P	0.997
2:86529365:A:G	S47P	0.997
2:86542303:A:G	W19R	0.997
2:86542303:A:T	W19R	0.997
2:86507479:C:A	G175W	0.996
2:86510365:A:C	M134R	0.996

dbSNP variants (sampled 300 via entrez): RS1000045302 (2:86564178 T>C), RS1000087562 (2:86519774 T>C,G), RS1000165959 (2:86512601 G>T), RS1000181248 (2:86533529 G>A,C,T), RS1000207748 (2:86516177 T>G), RS1000260214 (2:86515916 G>T), RS1000261216 (2:86559293 C>T), RS1000348655 (2:86553241 A>C,G), RS1000371370 (2:86555205 AT>A), RS1000490757 (2:86522967 T>A), RS1000503357 (2:86546169 C>A,T), RS1000576479 (2:86517350 A>T), RS1000597496 (2:86537883 C>G), RS1000619611 (2:86516191 T>C,G), RS1000660534 (2:86561064 T>C)

Disease associations

OMIM: gene MIM:610052 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003139_8	Glomerular filtration rate in chronic kidney disease	4.000000e-06
GCST006585_2477	Blood protein levels	9.000000e-07
GCST010105_113	Nicotine dependence symptom count	8.000000e-06
GCST010105_152	Nicotine dependence symptom count	8.000000e-06
GCST010988_183	Adult body size	8.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009262	nicotine dependence symptom count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
trichostatin A	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
FR900359	increases phosphorylation	1
bismuth tripotassium dicitrate	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Lead	affects splicing, affects expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	affects expression	1

Clinical trials (associated diseases)

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