CHMP4C
charged multivesicular body protein 4C, the group of Charged multivesicular body proteins|ESCRT-III
Basic information
Region (hg38): 8:81732447-81759515
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (9 variants)
- not provided (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHMP4C gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 10 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 9 | 0 | 1 |
Variants in CHMP4C
This is a list of pathogenic ClinVar variants found in the CHMP4C region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 8-81732681-G-C | not specified | Uncertain significance (Feb 17, 2024) | ||
| 8-81732744-C-G | not specified | Uncertain significance (May 04, 2022) | ||
| 8-81732798-G-C | not specified | Uncertain significance (Jul 09, 2021) | ||
| 8-81753066-G-A | not specified | Uncertain significance (Oct 27, 2021) | ||
| 8-81753179-C-A | not specified | Uncertain significance (Jan 22, 2024) | ||
| 8-81753201-G-A | not specified | Uncertain significance (Dec 19, 2023) | ||
| 8-81755372-A-G | not specified | Uncertain significance (Oct 26, 2022) | ||
| 8-81758142-G-A | not specified | Uncertain significance (Dec 06, 2021) | ||
| 8-81758194-A-G | not specified | Uncertain significance (Dec 18, 2023) | ||
| 8-81758206-T-C | not specified | Uncertain significance (Apr 19, 2023) | ||
| 8-81758209-G-A | not specified | Uncertain significance (Aug 17, 2022) | ||
| 8-81758284-G-A | not specified | Uncertain significance (Feb 07, 2023) | ||
| 8-81758290-G-A | not specified | Uncertain significance (Nov 10, 2022) | ||
| 8-81758536-G-A | Benign (Jan 18, 2019) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CHMP4C | protein_coding | protein_coding | ENST00000297265 | 5 | 27082 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 2.99e-7 | 0.326 | 113247 | 393 | 12108 | 125748 | 0.0510 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.145 | 129 | 124 | 1.04 | 0.00000643 | 1526 |
| Missense in Polyphen | 27 | 29.229 | 0.92374 | 401 | ||
| Synonymous | 0.437 | 42 | 45.8 | 0.918 | 0.00000228 | 432 |
| Loss of Function | 0.487 | 11 | 12.9 | 0.854 | 7.49e-7 | 132 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0673 | 0.0656 |
| Ashkenazi Jewish | 0.0788 | 0.0745 |
| East Asian | 0.000454 | 0.000435 |
| Finnish | 0.0433 | 0.0424 |
| European (Non-Finnish) | 0.0682 | 0.0655 |
| Middle Eastern | 0.000454 | 0.000435 |
| South Asian | 0.0697 | 0.0631 |
| Other | 0.0578 | 0.0534 |
dbNSFP
Source:
- Function
- 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 (PubMed:22422861, PubMed:24814515). 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 (PubMed:22660413). {ECO:0000269|PubMed:14505569, ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14519844, ECO:0000269|PubMed:22422861, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:24814515}.;
- Pathway
- Endocytosis - Homo sapiens (human);Necroptosis - Homo sapiens (human);Disease;Vesicle-mediated transport;Membrane Trafficking;Budding and maturation of HIV virion;Late Phase of HIV Life Cycle;HIV Life Cycle;HIV Infection;Endosomal Sorting Complex Required For Transport (ESCRT);Infectious disease
(Consensus)
Recessive Scores
- pRec
- 0.126
Intolerance Scores
- loftool
- 0.740
- rvis_EVS
- 0.1
- rvis_percentile_EVS
- 61.49
Haploinsufficiency Scores
- pHI
- 0.233
- hipred
- Y
- hipred_score
- 0.633
- ghis
- 0.489
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.652
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Chmp4c
- Phenotype
Gene ontology
- Biological process
- nucleus organization;vacuolar transport;mitotic metaphase plate congression;abscission;regulation of centrosome duplication;protein transport;endosomal transport;macroautophagy;viral life cycle;negative regulation of cytokinesis;multivesicular body assembly;viral budding via host ESCRT complex;mitotic cytokinesis checkpoint;regulation of viral process;midbody abscission;ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway;regulation of mitotic spindle assembly;positive regulation of viral release from host cell
- Cellular component
- ESCRT III complex;cytosol;midbody;late endosome membrane;Flemming body
- Molecular function
- protein binding;protein homodimerization activity