CHMP4C

Summary

CHMP4C (charged multivesicular body protein 4C, HGNC:30599) is a protein-coding gene on chromosome 8q21.13, encoding Charged multivesicular body protein 4c (Q96CF2). 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.

CHMP4C belongs to the chromatin-modifying protein/charged multivesicular body protein (CHMP) family. These proteins are components of ESCRT-III (endosomal sorting complex required for transport III), a complex involved in degradation of surface receptor proteins and formation of endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (MIM 164010), is required for both MVB formation and regulation of cell cycle progression (Tsang et al., 2006 [PubMed 16730941]).

Source: NCBI Gene 92421 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 57 total — 1 pathogenic
• MANE Select transcript: NM_152284

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30599
Approved symbol	CHMP4C
Name	charged multivesicular body protein 4C
Location	8q21.13
Locus type	gene with protein product
Status	Approved
Aliases	MGC22825, Shax3, VPS32C
Ensembl gene	ENSG00000164695
Ensembl biotype	protein_coding
OMIM	610899
Entrez	92421

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000297265

RefSeq mRNA: 1 — MANE Select: NM_152284 NM_152284

CCDS: CCDS6233

Canonical transcript exons

ENST00000297265 — 5 exons

Exon	Start	End
ENSE00001086645	81755370	81755484
ENSE00001086648	81758142	81758295
ENSE00001086651	81753064	81753241
ENSE00001086655	81758480	81759515
ENSE00001212540	81732448	81732816

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 98.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.7725 / max 137.9604, expressed in 919 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89551	4.3478	862
89552	1.3548	459
89550	0.0698	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	98.06	gold quality
jejunal mucosa	UBERON:0000399	97.06	gold quality
ileal mucosa	UBERON:0000331	96.82	gold quality
upper arm skin	UBERON:0004263	96.36	gold quality
esophagus squamous epithelium	UBERON:0006920	94.78	gold quality
palpebral conjunctiva	UBERON:0001812	94.69	gold quality
parotid gland	UBERON:0001831	93.01	gold quality
duodenum	UBERON:0002114	92.81	gold quality
epithelial cell of pancreas	CL:0000083	92.63	gold quality
lower esophagus mucosa	UBERON:0035834	91.97	gold quality
gingival epithelium	UBERON:0001949	91.49	gold quality
gingiva	UBERON:0001828	90.82	gold quality
colonic mucosa	UBERON:0000317	88.76	gold quality
skin of leg	UBERON:0001511	88.34	gold quality
skin of hip	UBERON:0001554	88.17	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.05	gold quality
zone of skin	UBERON:0000014	87.88	gold quality
body of pancreas	UBERON:0001150	87.76	gold quality
oral cavity	UBERON:0000167	86.57	gold quality
pancreas	UBERON:0001264	86.54	gold quality
skin of abdomen	UBERON:0001416	86.45	gold quality
esophagus mucosa	UBERON:0002469	86.36	gold quality
islet of Langerhans	UBERON:0000006	86.19	gold quality
mucosa of transverse colon	UBERON:0004991	86.02	gold quality
saliva-secreting gland	UBERON:0001044	85.80	gold quality
mouth mucosa	UBERON:0003729	84.69	gold quality
nasal cavity mucosa	UBERON:0001826	84.60	gold quality
rectum	UBERON:0001052	84.50	gold quality
minor salivary gland	UBERON:0001830	84.38	gold quality
epithelium of mammary gland	UBERON:0003244	84.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

36 targeting CHMP4C, 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-3924	100.00	72.09	2394
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-7705	98.69	67.47	543
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-4266	98.53	67.29	1035
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-4432	97.80	67.87	705
HSA-MIR-3189-5P	97.55	66.71	655
HSA-MIR-192-3P	97.52	67.66	1001
HSA-MIR-6509-5P	97.39	68.27	969

Literature-anchored findings (GeneRIF, showing 15)

• The Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4C. (PMID:18511562)
• findings show CHMP4C is involved in abscission timing; this function correlated with its differential spatiotemporal distribution during late stages of cytokinesis; CHMP4C functioned in the Aurora B-dependent abscission checkpoint (PMID:22422861)
• AURKB phosphorylates CHMP4C at 3 serines its C-terminal tail.Phosphorylation at these sites appears essential for CHMP4C function because their mutation leads to cytokinesis defects. (PMID:22724069)
• Single nucleotide polymorphisms in CHMP4C gene is associated with ovarian cancer. (PMID:23535730)
• CHMP4C mediates radiation resistance in lung cancer cells. (PMID:26712741)
• The ESCRT-III subunit CHMP4B is a key effector in abscission, whereas its paralogue, CHMP4C, is a component in the abscission checkpoint that delays abscission until chromatin is cleared from the intercellular bridge. (PMID:26929449)
• Results show that CHMP4C, under the regulation of the chromosomal passenger complex, binds to highly curved membranes and promotes the closure of membrane gaps. Two distinctly localized pools of phosphorylated CHMP4C exist during cytokinesisI but the phosphorylation is not required for its assembly into spiral filaments. Also, the centralspindlin complex associates preferentially with the with unphosphorylated form. (PMID:27784789)
• These results show that Chmp4c regulates the mitotic spindle checkpoint by promoting localization of the RZZ complex to unattached kinetochores. (PMID:29362225)
• The role of CHMP4C in the formation of stable kinetochore-microtubule attachments during the cell cycle is reported. (PMID:29562220)
• Chmp4c regulates kinetochore-microtubule interactions to promote accurate chromosome segregation.Chmp4c promotes Hec1 and Nuf2 kinetochore localization.Chmp4c binds and bundles microtubules. (PMID:29968190)
• Data demonstrate the biological importance of the abscission checkpoint and suggest that dysregulation of abscission by CHMP4CT232 may synergize with oncogene-induced mitotic stress to promote genomic instability and tumorigenesis. (PMID:30181294)
• Chromatin modified protein 4C (CHMP4C) facilitates the malignant development of cervical cancer cells. (PMID:32406588)
• Novel Role for ESCRT-III Component CHMP4C in the Integrity of the Endocytic Network Utilized for Herpes Simplex Virus Envelopment. (PMID:33975940)
• VPS32, a member of the ESCRT complex, modulates adherence to host cells in the parasite Trichomonas vaginalis by affecting biogenesis and cargo sorting of released extracellular vesicles. (PMID:34951683)
• Exploring the clinical and biological significance of the cell cycle-related gene CHMP4C in prostate cancer. (PMID:39138470)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chmp4c	ENSDARG00000007418
mus_musculus	Chmp4c	ENSMUSG00000027536
rattus_norvegicus	Chmp4c	ENSRNOG00000010238

Paralogs (5): CHMP5 (ENSG00000086065), CHMP4B (ENSG00000101421), CHMP7 (ENSG00000147457), CHMP4A (ENSG00000254505), CHMP4BP1 (ENSG00000258469)

Protein

Protein identifiers

Charged multivesicular body protein 4c — Q96CF2 (reviewed: Q96CF2)

Alternative names: Chromatin-modifying protein 4c, SNF7 homolog associated with Alix 3, SNF7-3, Vacuolar protein sorting-associated protein 32-3

All UniProt accessions (1): Q96CF2

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). Key component of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage: upon phosphorylation by AURKB, together with ZFYVE19/ANCHR, retains abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis. Deactivation of AURKB results in dephosphorylation of CHMP4C followed by its dissociation from ANCHR and VPS4 and subsequent abscission. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Involved in HIV-1 p6- and p9-dependent virus release. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan.

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. Self-associates. Interacts with CHMP2A. Interacts with CHMP4A. Interacts with CHMP4B. Interacts with CHMP6. Interacts with VPS4A. Interacts with PDCD6IP; the interaction is direct.

Subcellular location. Cytoplasm. Cytosol. Late endosome membrane. Midbody. Midbody ring.

Tissue specificity. Expressed in heart, spleen and kidney.

Post-translational modifications. Phosphorylated at Ser-210 by AURKB during cytokinesis: together with ZFYVE19/ANCHR, phosphorylated CHMP4C retains abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis.

Domain organisation. The acidic C-terminus and the basic N-terminus 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.

RefSeq proteins (1): NP_689497* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005024	Snf7_fam	Family

Pfam: PF03357

UniProt features (11 total): region of interest 4, chain 1, helix 1, coiled-coil region 1, compositionally biased region 1, modified residue 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5WA1	X-RAY DIFFRACTION	1.87
5V3R	X-RAY DIFFRACTION	1.91
5MK3	X-RAY DIFFRACTION	2
3C3R	X-RAY DIFFRACTION	2.02

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CF2-F1	77.26	0.39

Functional residue map

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

Post-translational modifications (1): 210

Mutagenesis-validated functional residues (1):

Position	Phenotype
210	abolishes localization to the flemming body and ability to delay abscission.

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: 244 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, 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_NEGATIVE_REGULATION_OF_CELL_DIVISION, GOBP_MEMBRANE_BIOGENESIS, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION

GO Biological Process (26): plasma membrane repair (GO:0001778), vesicle budding from membrane (GO:0006900), autophagy (GO:0006914), nucleus organization (GO:0006997), mitotic metaphase chromosome alignment (GO:0007080), regulation of centrosome duplication (GO:0010824), protein transport (GO:0015031), macroautophagy (GO:0016236), nuclear membrane reassembly (GO:0031468), negative regulation of cytokinesis (GO:0032466), 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), ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway (GO:0043162), mitotic cytokinesis checkpoint signaling (GO:0044878), 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), obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway (GO:0090611), autophagosome maturation (GO:0097352), regulation of mitotic spindle assembly (GO:1901673), late endosome to lysosome transport (GO:1902774), vacuolar transport (GO:0007034)

GO Molecular Function (2): protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (18): autophagosome membrane (GO:0000421), kinetochore (GO:0000776), ESCRT III complex (GO:0000815), nuclear pore (GO:0005643), lysosomal membrane (GO:0005765), multivesicular body (GO:0005771), kinetochore microtubule (GO:0005828), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic side of plasma membrane (GO:0009898), midbody (GO:0030496), multivesicular body membrane (GO:0032585), Flemming body (GO:0090543), 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	5
vesicle-mediated transport	2
membrane organization	2
viral budding	2
vesicle fusion	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
regulation of centrosome cycle	1
centrosome duplication	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
autophagosome assembly	1
autophagy	1
membrane assembly	1
nuclear membrane organization	1
cytokinesis	1
negative regulation of cell cycle process	1
regulation of cytokinesis	1
negative regulation of cell division	1
endosome transport via multivesicular body sorting pathway	1
late endosome to vacuole transport	1
multivesicular body organization	1
organelle assembly	1
ubiquitin-dependent protein catabolic process	1
protein catabolic process in the vacuole	1
multivesicular body sorting pathway	1
mitotic cell cycle checkpoint signaling	1
negative regulation of G2/M transition of mitotic cell cycle	1

Protein interactions and networks

STRING

2055 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHMP4C	CHMP1A	Q9HD42	942
CHMP4C	CHMP5	Q9NZZ3	919
CHMP4C	VPS4B	O75351	908
CHMP4C	CHMP2A	O43633	905
CHMP4C	CHMP3	Q9Y3E7	898
CHMP4C	CC2D1A	Q6P1N0	891
CHMP4C	A0A140T963	A0A140T963	890
CHMP4C	PDCD6IP	Q8WUM4	887
CHMP4C	VPS25	Q9BRG1	856
CHMP4C	VPS4A	Q9UN37	850
CHMP4C	TSG101	Q99816	849
CHMP4C	CHMP2B	Q9UQN3	832
CHMP4C	CHMP1B	Q7LBR1	817
CHMP4C	IST1	P53990	803
CHMP4C	CEP55	Q53EZ4	800

IntAct

23 interactions, top by confidence:

A	B	Type	Score
PDCD6IP	CHMP4C	psi-mi:“MI:0407”(direct interaction)	0.670
CHMP4C	PDCD6IP	psi-mi:“MI:0915”(physical association)	0.670
CHMP4C	USP8	psi-mi:“MI:0915”(physical association)	0.610
USP8	CHMP4C	psi-mi:“MI:0407”(direct interaction)	0.610
CHMP4C		psi-mi:“MI:0915”(physical association)	0.560
	CHMP4C	psi-mi:“MI:0915”(physical association)	0.560
CHMP4B	CHMP4C	psi-mi:“MI:0915”(physical association)	0.550
USP54	CHMP4C	psi-mi:“MI:0407”(direct interaction)	0.440
BROX	CHMP4C	psi-mi:“MI:0915”(physical association)	0.400
VPS4A	CHMP4C	psi-mi:“MI:0915”(physical association)	0.400
ZFYVE19	CHMP4C	psi-mi:“MI:0915”(physical association)	0.400
CHMP4C	STAMBP	psi-mi:“MI:0915”(physical association)	0.400
TRPC4AP	CHMP4C	psi-mi:“MI:0915”(physical association)	0.370
CC2D1A	CHMP4C	psi-mi:“MI:0915”(physical association)	0.370
CHMP7	CHMP4C	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
IGHA1	PLG	psi-mi:“MI:0914”(association)	0.350
CHMP4C	DNM1L	psi-mi:“MI:0914”(association)	0.350

BioGRID (697): HMGB3P1 (Two-hybrid), CHMP1B (Co-fractionation), CHMP4C (Co-fractionation), CHMP4C (Affinity Capture-MS), CHMP4C (Affinity Capture-Western), CHMP4C (Synthetic Lethality), CHMP4C (Affinity Capture-MS), SPTAN1 (Affinity Capture-MS), ACTN4 (Affinity Capture-MS), FLNA (Affinity Capture-MS), SPTBN1 (Affinity Capture-MS), ACTN1 (Affinity Capture-MS), TOP2A (Affinity Capture-MS), CHMP4C (Affinity Capture-MS), LMNA (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: A2VDY3, O82197, P0C149, P0CR54, P0CR55, P39929, P59074, Q569C1, Q5ABD0, Q5B5E0, Q5XGW6, Q5ZHP5, Q6BSH2, Q6CBS3, Q6CJL0, Q6FW96, Q6GL11, Q6GNN8, Q6IQ73, Q753W3, Q7ZVC4, Q86H98, Q871Y8, Q8T0Q4, Q96CF2, Q9BY43, Q9D7F7, Q9D8B3, Q9H444, Q9P7F7, Q9SZE4, Q54KZ4, Q7T0X5, Q86K93, Q9VVI9, Q5R861, Q96FZ7, O74422, P0C0A3, Q54JK4

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
AURKB	up-regulates	CHMP4C	phosphorylation
ULK3	“down-regulates activity”	CHMP4C	phosphorylation
CHMP4C	“form complex”	ESCRT-III	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 16 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.

GO biological processes:

GO term	Partners	Fold	FDR
midbody abscission	5	261.7×	9e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	48
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
443624	GRCh37/hg19 8q21.11-21.13(chr8:77751515-83516216)x1	Pathogenic

SpliceAI

591 predictions. Top by Δscore:

Variant	Effect	Δscore
8:81753062:A:AG	acceptor_gain	1.0000
8:81753062:AGCT:A	acceptor_gain	1.0000
8:81753063:G:GA	acceptor_gain	1.0000
8:81753063:GC:G	acceptor_gain	1.0000
8:81753063:GCT:G	acceptor_gain	1.0000
8:81753063:GCTG:G	acceptor_gain	1.0000
8:81753063:GCTGC:G	acceptor_gain	1.0000
8:81753187:TGTTG:T	donor_gain	1.0000
8:81753237:AACAT:A	donor_gain	1.0000
8:81753238:ACAT:A	donor_gain	1.0000
8:81753238:ACATG:A	donor_loss	1.0000
8:81753239:CAT:C	donor_gain	1.0000
8:81753239:CATGT:C	donor_loss	1.0000
8:81753240:AT:A	donor_gain	1.0000
8:81753240:ATGT:A	donor_loss	1.0000
8:81753241:TG:T	donor_loss	1.0000
8:81753242:G:C	donor_loss	1.0000
8:81753242:G:GG	donor_gain	1.0000
8:81753243:T:A	donor_loss	1.0000
8:81753244:GAGT:G	donor_loss	1.0000
8:81755368:AGG:A	acceptor_gain	1.0000
8:81755369:GGG:G	acceptor_gain	1.0000
8:81755482:GAG:G	donor_gain	1.0000
8:81755484:GGT:G	donor_loss	1.0000
8:81755485:G:GA	donor_loss	1.0000
8:81755485:G:GG	donor_gain	1.0000
8:81755486:T:A	donor_loss	1.0000
8:81758133:T:TA	acceptor_gain	1.0000
8:81758135:T:TA	acceptor_gain	1.0000
8:81758140:A:AG	acceptor_gain	1.0000

AlphaMissense

1541 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:81753156:G:C	A95P	0.998
8:81732787:C:A	A54D	0.997
8:81753075:G:C	A68P	0.996
8:81753109:T:C	L79P	0.996
8:81753130:T:C	L86P	0.996
8:81753168:T:C	S99P	0.996
8:81753216:G:C	A115P	0.996
8:81732754:T:C	L43P	0.995
8:81753089:G:C	K72N	0.995
8:81753089:G:T	K72N	0.995
8:81753210:G:C	A113P	0.995
8:81732712:T:C	L29P	0.994
8:81758161:T:C	L168P	0.994
8:81753160:T:C	L96P	0.993
8:81732786:G:C	A54P	0.991
8:81753067:C:A	A65E	0.991
8:81753079:T:C	L69P	0.991
8:81732745:A:C	Q40P	0.990
8:81753148:A:C	Q92P	0.990
8:81753208:C:A	A112E	0.989
8:81753132:T:C	S87P	0.988
8:81758149:T:C	L164S	0.988
8:81732743:A:C	K39N	0.985
8:81732743:A:T	K39N	0.985
8:81732763:G:C	R46P	0.984
8:81732733:T:C	L36P	0.983
8:81753066:G:C	A65P	0.982
8:81755435:T:G	I145S	0.982
8:81753207:G:C	A112P	0.981
8:81753087:A:G	K72E	0.980

dbSNP variants (sampled 300 via entrez): RS1000108790 (8:81746668 G>A), RS1000116677 (8:81739919 G>A), RS1000133895 (8:81734328 G>A), RS1000246648 (8:81747462 C>T), RS1000356588 (8:81731459 A>C), RS1000382483 (8:81734405 A>G), RS1000555815 (8:81759572 A>G), RS1000562771 (8:81744846 G>A,T), RS1000928234 (8:81754857 C>T), RS1000986257 (8:81733304 T>A), RS1001133533 (8:81738379 C>T), RS1001189636 (8:81742601 G>A), RS1001200948 (8:81748727 A>G), RS1001258840 (8:81734390 G>A), RS1001302186 (8:81740295 G>A,T)

Disease associations

OMIM: gene MIM:610899 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001941_13	Ovarian cancer	6.000000e-09
GCST001941_17	Ovarian cancer	7.000000e-10
GCST002748_7	Epithelial ovarian cancer	3.000000e-10
GCST012442_49	Age-related hearing impairment	2.000000e-20

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases expression	3
mercuric bromide	increases expression, affects cotreatment	2
Calcitriol	increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tobacco Smoke Pollution	affects expression, increases expression	2
fluorene-9-bisphenol	increases expression	1
dicrotophos	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	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
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
Sunitinib	increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	decreases expression	1
Folic Acid	increases expression	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tretinoin	increases expression	1
Triclosan	decreases expression	1
Urethane	increases expression	1

Clinical trials (associated diseases)

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