CHMP6

Summary

CHMP6 (charged multivesicular body protein 6, HGNC:25675) is a protein-coding gene on chromosome 17q25.3, encoding Charged multivesicular body protein 6 (Q96FZ7). 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 common-essential gene (DepMap: required in 100.0% of cancer cell lines).

This gene encodes a member of the chromatin-modifying protein/charged multivesicular body protein family. Proteins in this family are part of the ESCRT-III (endosomal sorting complex required for transport III) which degrades surface receptors, and in biosynthesis of endosomes.

Source: NCBI Gene 79643 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 48 total
• GTEx eGene: eQTL in 37 tissues, sQTL in 2 (q < 0.05)
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.76 (intermediate), LOEUF 0.60 (moderately constrained)
• MANE Select transcript: NM_024591

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25675
Approved symbol	CHMP6
Name	charged multivesicular body protein 6
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11749, VPS20
Ensembl gene	ENSG00000176108
Ensembl biotype	protein_coding
OMIM	610901
Entrez	79643

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 3 nonsense_mediated_decay

MANE Select: ENST00000325167

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 2

ENST00000325167, ENST00000571457, ENST00000572525, ENST00000572778, ENST00000979700, ENST00001054363, ENST00001054366, ENST00001054367, ENST00001124001, ENST00001130641, ENST00001143775

RefSeq mRNA: 1 — MANE Select: NM_024591 NM_024591

CCDS: CCDS11774

Canonical transcript exons

ENST00000325167 — 8 exons

Exon	Start	End
ENSE00001267170	80998366	80998420
ENSE00001267177	80997261	80997341
ENSE00001267183	80997007	80997072
ENSE00001267186	80995672	80995758
ENSE00001267207	80999098	81000133
ENSE00001290339	80991841	80991981
ENSE00003480443	80994581	80994690
ENSE00003563810	80995019	80995106

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 91.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.8929 / max 148.7481, expressed in 1806 samples.

Highest expression (Bgee): apex of heart, gastrocnemius, hindlimb stylopod muscle, mucosa of transverse colon, muscle of leg.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CHMP6 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 37 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 39 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	2.2e-35	-0.27	17:80999674:T:C
Thyroid	eqtl	6.4e-23	-0.27	17:81006575:T:C
Cells Cultured fibroblasts	eqtl	3.5e-21	-0.27	17:81000101:C:G
Skin Sun Exposed Lower leg	eqtl	2.9e-17	-0.19	17:80993286:C:T
Adipose Visceral Omentum	eqtl	1.0e-14	-0.21	17:81000101:C:G
Pancreas	eqtl	8.8e-14	-0.32	17:81000101:C:G
Whole Blood	eqtl	1.1e-12	+0.14	17:80996699:C:T
Nerve Tibial	eqtl	1.7e-12	-0.20	17:80997109:A:G
Skin Not Sun Exposed Suprapubic	eqtl	3.3e-12	-0.19	17:81000101:C:G
Heart Left Ventricle	eqtl	4.1e-11	-0.24	17:80999674:T:C
Heart Atrial Appendage	eqtl	1.2e-10	-0.25	17:80999674:T:C
Prostate	eqtl	1.8e-10	-0.29	17:81000101:C:G
Testis	eqtl	3.9e-09	-0.25	17:81000101:C:G
Spleen	eqtl	5.9e-09	-0.25	17:81000101:C:G
Esophagus Muscularis	eqtl	1.0e-08	-0.19	17:81000101:C:G
Esophagus Mucosa	eqtl	1.8e-08	-0.16	17:81000101:C:G
Artery Aorta	eqtl	2.2e-08	-0.17	17:80998869:C:T
Artery Tibial	eqtl	2.3e-08	-0.14	17:80999674:T:C
Liver	eqtl	1.9e-07	-0.29	17:80999674:T:C
Colon Transverse	eqtl	3.2e-07	-0.13	17:81000101:C:G

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
163281	11.4448	1802
163282	2.4481	1420

Top tissues by expression

showing 100 of 277 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	91.34	gold quality
gastrocnemius	UBERON:0001388	90.93	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.47	gold quality
mucosa of transverse colon	UBERON:0004991	90.42	gold quality
muscle of leg	UBERON:0001383	90.39	gold quality
monocyte	CL:0000576	90.05	gold quality
mononuclear cell	CL:0000842	89.87	gold quality
granulocyte	CL:0000094	89.60	gold quality
leukocyte	CL:0000738	89.59	gold quality
right lobe of liver	UBERON:0001114	88.66	gold quality
sural nerve	UBERON:0015488	88.59	gold quality
muscle organ	UBERON:0001630	88.20	gold quality
stromal cell of endometrium	CL:0002255	87.57	gold quality
transverse colon	UBERON:0001157	87.32	gold quality
ectocervix	UBERON:0012249	86.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.38	gold quality
heart left ventricle	UBERON:0002084	86.35	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.22	gold quality
esophagus mucosa	UBERON:0002469	86.12	gold quality
cardiac ventricle	UBERON:0002082	86.07	gold quality
lower esophagus	UBERON:0013473	86.02	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.02	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.02	gold quality
skin of leg	UBERON:0001511	85.99	gold quality
body of uterus	UBERON:0009853	85.95	gold quality
left coronary artery	UBERON:0001626	85.92	gold quality
endocervix	UBERON:0000458	85.85	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.84	gold quality
spleen	UBERON:0002106	85.79	gold quality
lower esophagus mucosa	UBERON:0035834	85.78	gold quality
esophagus	UBERON:0001043	85.76	gold quality
mucosa of stomach	UBERON:0001199	85.68	gold quality
upper lobe of left lung	UBERON:0008952	85.66	gold quality
body of stomach	UBERON:0001161	85.62	gold quality
coronary artery	UBERON:0001621	85.62	gold quality
tibial artery	UBERON:0007610	85.55	gold quality
popliteal artery	UBERON:0002250	85.54	gold quality
metanephros cortex	UBERON:0010533	85.40	gold quality
skin of abdomen	UBERON:0001416	85.38	gold quality
right adrenal gland cortex	UBERON:0035827	85.37	gold quality
aorta	UBERON:0000947	85.36	gold quality
thoracic aorta	UBERON:0001515	85.27	gold quality
right lobe of thyroid gland	UBERON:0001119	85.25	gold quality
ascending aorta	UBERON:0001496	85.22	gold quality
right atrium auricular region	UBERON:0006631	85.16	gold quality
right adrenal gland	UBERON:0001233	85.11	gold quality
left uterine tube	UBERON:0001303	85.00	gold quality
rectum	UBERON:0001052	84.94	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.94	gold quality
right coronary artery	UBERON:0001625	84.92	gold quality
left lobe of thyroid gland	UBERON:0001120	84.87	gold quality
tibial nerve	UBERON:0001323	84.87	gold quality
blood	UBERON:0000178	84.80	gold quality
heart	UBERON:0000948	84.75	gold quality
left adrenal gland	UBERON:0001234	84.74	gold quality
left adrenal gland cortex	UBERON:0035825	84.74	gold quality
adenohypophysis	UBERON:0002196	84.61	gold quality
prefrontal cortex	UBERON:0000451	84.60	gold quality
upper lobe of lung	UBERON:0008948	84.58	gold quality
descending thoracic aorta	UBERON:0002345	84.57	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.37	gold quality
smooth muscle tissue	UBERON:0001135	84.36	gold quality
adrenal cortex	UBERON:0001235	84.28	gold quality
minor salivary gland	UBERON:0001830	84.26	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	84.21	gold quality
colon	UBERON:0001155	84.18	gold quality
right uterine tube	UBERON:0001302	84.11	gold quality
right ovary	UBERON:0002118	84.09	gold quality
stomach	UBERON:0000945	84.05	gold quality
thyroid gland	UBERON:0002046	84.04	gold quality
cardiac atrium	UBERON:0002081	83.94	gold quality
small intestine	UBERON:0002108	83.92	gold quality
body of pancreas	UBERON:0001150	83.80	gold quality
large intestine	UBERON:0000059	83.73	gold quality
islet of Langerhans	UBERON:0000006	83.72	gold quality
intestine	UBERON:0000160	83.59	gold quality
adrenal gland	UBERON:0002369	83.55	gold quality
left ovary	UBERON:0002119	83.51	gold quality
skeletal muscle tissue	UBERON:0001134	83.46	gold quality
omental fat pad	UBERON:0010414	83.46	gold quality
right lung	UBERON:0002167	83.45	gold quality
peritoneum	UBERON:0002358	83.44	gold quality
zone of skin	UBERON:0000014	83.41	gold quality
pituitary gland	UBERON:0000007	83.34	gold quality
spinal cord	UBERON:0002240	83.33	gold quality
anterior cingulate cortex	UBERON:0009835	83.32	gold quality
cingulate cortex	UBERON:0003027	83.28	gold quality
mouth mucosa	UBERON:0003729	83.20	gold quality
saliva-secreting gland	UBERON:0001044	83.17	gold quality
right frontal lobe	UBERON:0002810	83.03	gold quality
adipose tissue of abdominal region	UBERON:0007808	83.01	gold quality
ganglionic eminence	UBERON:0004023	82.92	gold quality
amygdala	UBERON:0001876	82.89	gold quality
cortical plate	UBERON:0005343	82.89	gold quality
pancreas	UBERON:0001264	82.85	gold quality
fundus of stomach	UBERON:0001160	82.76	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.69	gold quality
ventricular zone	UBERON:0003053	82.61	gold quality
adult mammalian kidney	UBERON:0000082	82.49	gold quality
triceps brachii	UBERON:0001509	82.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.90

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	42.3	not detected
Frontal cortex	tissue	37.0
Tongue	tissue	27.3
Caudate putamen	tissue	27.2
Hippocampus	tissue	22.8	low
Cerebral cortex	tissue	21.2	medium
Motor cortex	tissue	21.2
Choroid plexus	tissue	20.5
Thalamus	tissue	20.4
Somatosensory cortex	tissue	20.4
Pons	tissue	20.2
Locus coeruleus	tissue	19.8
Prefrontal cortex	tissue	19.6
Nucleus accumbens	tissue	19.5
Superior colliculi	tissue	18.8
Hippocampal formation	tissue	18.8
Midbrain	tissue	18.3
Putamen	tissue	18.0
Entorhinal cortex	tissue	18.0
Occipital cortex	tissue	18.0
Parathyroid gland	tissue	17.9	high
Retrosplenial cortex	tissue	17.9
Temporal cortex	tissue	17.8
Postcentral gyrus	tissue	17.7
Insular cortex	tissue	17.6
Substantia nigra	tissue	17.4
Retrosplenial and cingulate cortex	tissue	17.3
Retina	tissue	17.2
Vagina	tissue	17.0	not detected
Medulla oblongata	tissue	17.0
Hypothalamus	tissue	17.0
Liver	tissue	16.7	medium
Basal ganglia	tissue	16.3	low
Ventral forebrain	tissue	16.3
Septum	tissue	16.3
Colon	tissue	16.1	medium
Smooth muscle	tissue	16.0	not detected
Thymus	tissue	16.0
Spinal cord	tissue	15.7
Pituitary gland	tissue	15.6
Ovary	tissue	15.2	low
Periaqueductal gray	tissue	15.2
Skin 1	tissue	15.1	low
Amygdala	tissue	15.0
Rectum	tissue	14.6	medium
Spleen	tissue	14.5	low
Small intestine	tissue	14.2	medium
Stomach 1	tissue	13.8	medium
Tonsil	tissue	13.7	medium
Adipose tissue	tissue	13.4	medium
Lymph node	tissue	13.2	medium
Salivary gland	tissue	13.2	low
Fallopian tube	tissue	13.2	high
Placenta	tissue	12.8	medium
Lung	tissue	12.8	medium
Heart muscle	tissue	12.7	low
Appendix	tissue	12.7	medium
Corpus callosum	tissue	12.6
Pancreas	tissue	12.4	medium
Duodenum	tissue	12.4	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Parieto-temporal junction (white matter) (29.2), Temporal white matter (28.9), Nucleus ambiguus (28.5), Precentral gyrus (25.8), Lateral amygdala (25.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CHMP6 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

26 miRNAs:

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-185-3P	99.95	67.01	1743
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-3155A	98.16	66.09	965
HSA-MIR-3155B	98.16	66.09	965
HSA-MIR-503-5P	97.87	66.83	575
HSA-MIR-1226-3P	97.51	66.32	1063
HSA-MIR-134-3P	96.83	66.22	1001
HSA-MIR-1233-3P	96.81	65.44	573
HSA-MIR-3918	96.13	64.65	1300
HSA-MIR-4300	95.85	64.56	1003
HSA-MIR-5591-5P	95.85	64.76	1002
HSA-MIR-6720-3P	91.34	60.49	67
HSA-MIR-3195	88.05	57.43	53

Functional genomics

gnomAD constraint: pLI 0.761, LOEUF 0.599, missense Z -0.516 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000325167 — one region, missense o/e 1.02. DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): Panc 08.13 (-3.053), TYK-nu (-3.041), HCC1937 (-3.012), VCaP (-2.902), NCI-H1092 (-2.847), SNU-308 (-2.837), Lu-65 (-2.799), Panc 10.05 (-2.774), EFO-21 (-2.73), HPAF-II (-2.711), TUHR10TKB (-2.693), KP-N-SI9s (-2.648), RPMI-7951 (-2.635), G-402 (-2.635), EC-GI-10 (-2.624).

Literature-anchored findings (GeneRIF, showing 6)

• In this study, we found that overexpression of chromatin modifying protein 6 (CHMP6) induced cell death by a series of experiments. (PMID:19270365)
• Results describe the mapping of multivesicular bodies with the second winged helix domain of human ESCRT-II subunit VPS25 and the first helix of ESCRT-III subunit VPS20. (PMID:19686684)
• silencing CHMP6 and VPS4A also blocked epidermal growth factor receptor (EGFR) recycling (PMID:22231449)
• Taken together, these data suggest an active role for ESCRT-II and CHMP6 in ESCRT-mediated abscission (PMID:25232011)
• Purified VPS-20 exhibits an open extended conformation, irrespective of ESCRT-II binding. (PMID:25588614)
• ELK4 targets CHMP6 to inhibit ferroptosis and enhance malignant properties of skin cutaneous melanoma cells. (PMID:39305302)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	chmp6a	ENSDARG00000097451
danio_rerio	chmp6b	ENSDARG00000102024
mus_musculus	Chmp6	ENSMUSG00000025371
rattus_norvegicus	Chmp6	ENSRNOG00000004014
drosophila_melanogaster	Vps20	FBGN0034744
caenorhabditis_elegans	vps-20	WBGENE00022027

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:3583942) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
preweaning lethality, complete penetrance	1
embryonic lethality prior to organogenesis	1
prenatal lethality prior to heart atrial septation	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R861	99.5%	Diamond
Xenopus laevis	Q6GMA4	95.5%	Diamond
Gallus gallus	Q5ZL55	81.6%	Diamond
Arabidopsis thaliana	Q8GXN6	80.1%	Diamond
Debaryomyces hansenii CBS767	Q6BSH2	69.9%	Diamond
Pyricularia oryzae 70-15	P0C149	68.7%	Diamond
Saccharomyces cerevisiae S288C	P39929	61.8%	Diamond
Dictyostelium discoideum	Q54KZ4	42.8%	Diamond
Schizosaccharomyces pombe 972h-	O94318	39.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
RPTOR	protein-coding	57521
BAIAP2-DT	ncRNA	440465
BAIAP2	protein-coding	10458
LMTK1	protein-coding	9625
NPTX1	protein-coding	4884

Protein

Protein identifiers

Charged multivesicular body protein 6 — Q96FZ7 (reviewed: Q96FZ7)

Alternative names: Chromatin-modifying protein 6, Vacuolar protein sorting-associated protein 20

All UniProt accessions (4): Q96FZ7, I3L3E4, I3L4A1, I3L4G8

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. In the ESCRT-III complex, it probably serves as an acceptor for the ESCRT-II complex on endosomal membranes.

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. Interacts with VPS4A; the interaction is direct. Interacts with VPS4B; the interaction is direct. Interacts with CHMP4A, CHMP4B and CHMP4C. Interacts with SNF8, VPS25 and VPS36.

Subcellular location. Endomembrane system. Endosome membrane. Late endosome membrane. Membrane.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. ISGylated in a CHMP5-dependent manner. Isgylation weakens its interaction with VPS4A.

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.

Similarity. Belongs to the SNF7 family.

RefSeq proteins (1): NP_078867* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005024	Snf7-like	Family

Pfam: PF03357

UniProt features (18 total): mutagenesis site 6, sequence conflict 2, modified residue 2, initiator methionine 1, chain 1, helix 1, region of interest 1, coiled-coil region 1, short sequence motif 1, lipid moiety-binding region 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
3HTU	Crystal structure of the human VPS25-VPS20 subcomplex	X-RAY DIFFRACTION	2
2K3W	NMR structure of VPS4A-MIT-CHMP6	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96FZ7-F1	82.51	0.54

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

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 (3)

Type	Positions
Phosphoserine	119
Phosphothreonine	130
N-myristoyl glycine	2

Mutagenesis-validated functional residues (6)

Position	Phenotype
49	does not affect the subcellular location.
168–201	membrane association; releases autoinhibition.
170	abolishes interaction with vps4a.
173	abolishes interaction with vps4a.
178	reduces interaction with vps4a.
2	abolishes myristoylation.

Function

Pathways and Gene Ontology

Reactome pathways

7 curated (TAS) of 31; 15 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

31 pathways:

ID	Pathway	Evidence
R-HSA-162588	Budding and maturation of HIV virion ⚕	curated
R-HSA-9610379	HCMV Late Events ⚕	curated
R-HSA-9679504	Translation of Replicase and Assembly of the Replication Transcription Complex ⚕	curated
R-HSA-917729	Endosomal Sorting Complex Required For Transport (ESCRT)	curated
R-HSA-1632852	Macroautophagy	curated
R-HSA-5620971	Pyroptosis	curated
R-HSA-9668328	Sealing of the nuclear envelope (NE) by ESCRT-III	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-9772572	Early SARS-CoV-2 Infection Events ⚕	—
R-HSA-9609646	HCMV Infection ⚕	—
R-HSA-162906	HIV Infection ⚕	—
R-HSA-162587	HIV Life Cycle ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-162599	Late Phase of HIV Life Cycle ⚕	—
R-HSA-9679506	SARS-CoV Infections ⚕	—
R-HSA-9678108	SARS-CoV-1 Infection ⚕	—
R-HSA-9694516	SARS-CoV-2 Infection ⚕	—
R-HSA-9694676	Translation of Replicase and Assembly of the Replication Transcription Complex ⚕	electronic
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-9612973	Autophagy	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-9615710	Late endosomal microautophagy	electronic
R-HSA-68886	M Phase	—
R-HSA-199991	Membrane Trafficking	—
R-HSA-68882	Mitotic Anaphase	—
R-HSA-2555396	Mitotic Metaphase and Anaphase	—
R-HSA-2995410	Nuclear Envelope (NE) Reassembly	—
R-HSA-5357801	Programmed Cell Death	—
R-HSA-5218859	Regulated Necrosis	—
R-HSA-5653656	Vesicle-mediated transport	—

MSigDB gene sets: 278 (showing top): GOBP_MITOTIC_CYTOKINESIS, REACTOME_ENDOSOMAL_SORTING_COMPLEX_REQUIRED_FOR_TRANSPORT_ESCRT, GOBP_CHROMOSOME_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_TYROSINE_KINASE_ACTIVITY, GOBP_NUCLEAR_MEMBRANE_REASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_PEPTIDYL_TYROSINE_PHOSPHORYLATION, GOBP_LYSOSOMAL_TRANSPORT, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_ENDOSOME_ORGANIZATION, GOBP_VACUOLE_ORGANIZATION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_VESICLE_LOCALIZATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GOBP_MEMBRANE_BIOGENESIS

GO Biological Process (25): plasma membrane repair (GO:0001778), vesicle budding from membrane (GO:0006900), autophagy (GO:0006914), nucleus organization (GO:0006997), mitotic metaphase chromosome alignment (GO:0007080), negative regulation of epidermal growth factor-activated receptor activity (GO:0007175), protein transport (GO:0015031), macroautophagy (GO:0016236), nuclear membrane reassembly (GO:0031468), late endosome to vacuole transport via multivesicular body sorting pathway (GO:0032511), multivesicular body assembly (GO:0036258), viral budding via host ESCRT complex (GO:0039702), regulation of protein catabolic process (GO:0042176), ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway (GO:0043162), viral budding from plasma membrane (GO:0046761), 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), ESCRT III complex assembly (GO:1904902), vacuolar transport (GO:0007034)

GO Molecular Function (2): protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (18): autophagosome membrane (GO:0000421), kinetochore (GO:0000776), ESCRT III complex (GO:0000815), nuclear envelope (GO:0005635), nuclear pore (GO:0005643), lysosomal membrane (GO:0005765), multivesicular body (GO:0005771), kinetochore microtubule (GO:0005828), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome membrane (GO:0010008), membrane (GO:0016020), midbody (GO:0030496), multivesicular body membrane (GO:0032585), extracellular exosome (GO:0070062), amphisome membrane (GO:1904930), endomembrane system (GO:0012505), late endosome membrane (GO:0031902)

Reactome top-level categories

15 top-level categories:

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
HIV Infection	1
HIV Life Cycle	1
Viral Infection Pathways	1
Vesicle-mediated transport	1
M Phase	1
Mitotic Anaphase	1
Programmed Cell Death	1

GO top-level categories

showing 60 of 73 GO namespaces:

Category	Terms
cellular anatomical structure	4
membrane organization	3
vesicle-mediated transport	2
viral budding	2
vesicle fusion	2
binding	2
endosome membrane	2
late endosome	2
plasma membrane organization	1
wound healing	1
vesicle organization	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
organelle organization	1
mitotic sister chromatid segregation	1
mitotic cell cycle	1
metaphase chromosome alignment	1
mitotic cell cycle process	1
epidermal growth factor receptor activity	1
negative regulation of epidermal growth factor receptor signaling pathway	1
negative regulation of protein tyrosine kinase activity	1
negative regulation of signaling receptor activity	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
autophagosome assembly	1
autophagy	1
membrane assembly	1
nuclear membrane organization	1
endosome transport via multivesicular body sorting pathway	1
late endosome to vacuole transport	1
multivesicular body organization	1
organelle assembly	1
regulation of catabolic process	1
protein catabolic process	1
regulation of protein metabolic process	1
ubiquitin-dependent protein catabolic process	1
protein catabolic process in the vacuole	1
multivesicular body sorting pathway	1
non-lytic viral release	1
vacuole fusion	1
endosome to lysosome transport via multivesicular body sorting pathway	1
lysosomal membrane organization	1
mitotic cytokinetic process	1
vacuolar membrane	1
autophagosome	1
condensed chromosome, centromeric region	1
intracellular membraneless organelle	1
supramolecular complex	1
ESCRT complex	1
membrane protein complex	1
nucleus	1
endomembrane system	1
organelle envelope	1
nuclear envelope	1
nuclear protein-containing complex	1
lysosome	1
lytic vacuole membrane	1
spindle microtubule	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 28 of 45 annotations. The rest are phylogenetic / computational / electronic (IEA).

28 experimentally-supported GO terms:

GO term	NS	Evidence
autophagosome maturation	BP	mutant phenotype
autophagy	BP	mutant phenotype
late endosome to lysosome transport	BP	mutant phenotype
midbody abscission	BP	mutant phenotype
mitotic metaphase chromosome alignment	BP	mutant phenotype
multivesicular body sorting pathway	BP	direct assay
negative regulation of epidermal growth factor-activated receptor activity	BP	mutant phenotype
nuclear membrane reassembly	BP	mutant phenotype
nucleus organization	BP	mutant phenotype
plasma membrane repair	BP	direct assay
regulation of mitotic spindle assembly	BP	mutant phenotype
regulation of protein catabolic process	BP	mutant phenotype
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	BP	direct assay
viral budding from plasma membrane	BP	direct assay
viral budding via host ESCRT complex	BP	direct assay
ESCRT III complex	CC	direct assay
amphisome membrane	CC	direct assay
autophagosome membrane	CC	direct assay
endosome membrane	CC	direct assay
extracellular exosome	CC	high-throughput assay
kinetochore	CC	direct assay
kinetochore microtubule	CC	direct assay
lysosomal membrane	CC	direct assay
membrane	CC	high-throughput assay
midbody	CC	direct assay
multivesicular body membrane	CC	direct assay
plasma membrane	CC	direct assay
protein-containing complex binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 931 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHMP6	CHMP3	Q9Y3E7	993
CHMP6	A0A140T963	A0A140T963	993
CHMP6	VPS25	Q9BRG1	992
CHMP6	VPS4A	Q9UN37	988
CHMP6	VPS36	Q86VN1	981
CHMP6	CHMP2A	O43633	976
CHMP6	SNF8	Q96H20	973
CHMP6	CHMP1A	Q9HD42	943
CHMP6	VPS28	Q9UK41	938
CHMP6	CHMP5	Q9NZZ3	931
CHMP6	VPS4B	O75351	874
CHMP6	IST1	P53990	833
CHMP6	EGF	P01133	819
CHMP6	VTA1	Q9NP79	800
CHMP6	CC2D1A	Q6P1N0	798

IntAct

Human interaction partners of CHMP6 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

17 partners by confidence:

Partner	Interaction type	MIscore	Records
VPS25	physical association	0.810	7
DNM2	physical association	0.560	3
SMN1	physical association	0.560	3
TOR1A	physical association	0.560	3
CHMP4B	physical association	0.550	1
USP54	direct interaction	0.440	1
USP8	direct interaction	0.440	1
PRDM10	physical association	0.400	1
CDK13	physical association	0.370	1
ELOF1	physical association	0.370	1
METTL9	physical association	0.370	1
PA	physical association	0.370	1
TNPO3	physical association	0.370	1
TRPC4AP	physical association	0.370	1
TTC19	physical association	0.370	1
ALDH1A2	association	0.350	1
RAB17	physical association	0.000	1

BioGRID (64 interactions; top human partners by supporting records): VPS25 (Two-hybrid; 12 records), CHMP4B (Affinity Capture-MS; 5 records), KRAS (Negative Genetic; 3 records), SNF8 (Affinity Capture-MS; 3 records), TSG101 (Affinity Capture-Western; 2 records), VPS36 (Affinity Capture-MS; 2 records), ALDH1A2 (Affinity Capture-MS), ARID1A (Negative Genetic), BAIAP2 (Affinity Capture-MS), C1orf27 (Affinity Capture-MS), CC2D2B (Cross-Linking-MS (XL-MS)), CCDC8 (Affinity Capture-MS), CLK3 (Affinity Capture-MS), EDEM1 (Affinity Capture-MS), EGFR (Negative Genetic)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
CHMP6	“form complex”	ESCRT-III	binding

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
ESCRT-III complex	10	CHMP6, CHMP2B, CHMP3, CHMP4A, CHMP5, CHMP1A, CHMP1B, CHMP2A, CHMP4B, CHMP4C

Disease & clinical

Genetic variants

Variant evidence for CHMP6: 48 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	2
Benign	3

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 526):

Position(s)	Effect	Δscore	Sites
17:80991982–80991983	donor_loss	1.0000	5
17:80994575	acceptor_gain	1.0000
17:80994579	acceptor_loss	1.0000
17:80994686	donor_gain	1.0000
17:80994691	donor_loss	1.0000	2
17:80995018	acceptor_loss	1.0000	2
17:80995263	donor_gain	1.0000
17:80995670–80995671	acceptor_loss	1.0000	6
17:80995759–80995760	donor_loss	1.0000	3
17:80997259–80997260	acceptor_loss	1.0000	6

AlphaMissense

386 missense substitutions predicted likely pathogenic (of 1,321 scored), across 129 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D17	8	0.981	0.993
D28	8	0.942	0.971
F5	8	0.797	0.928
F93	7	0.933	0.992
E92	7	0.808	0.916
E159	7	0.770	0.894
K24	6	0.972	0.996
L64	6	0.884	0.994
E97	6	0.875	0.951
V100	6	0.860	0.970
G2	6	0.859	0.960
M87	6	0.842	0.896
Q137	6	0.814	0.979
Q26	6	0.774	0.984
M114	6	0.770	0.921
D141	6	0.759	0.898
M118	6	0.700	0.758
G107	5	0.932	0.991
V13	5	0.889	0.980
L21	5	0.878	0.995

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.97e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000317
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000845

Disease associations

OMIM: gene MIM:610901 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
bisphenol A	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	increases abundance, decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
ferrous chloride	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
azoxystrobin	decreases expression	1
pyrimidifen	decreases expression	1
bisphenol B	increases expression	1
pyrachlostrobin	decreases expression	1
bisphenol S	increases expression	1
jinfukang	increases expression	1
picoxystrobin	decreases expression	1
bisphenol AF	increases expression	1
Zoledronic Acid	increases expression	1
Antimycin A	decreases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	affects expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.