CHMP4A
charged multivesicular body protein 4A, the group of Charged multivesicular body proteins|ESCRT-III
Basic information
Region (hg38): 14:24209615-24213830
Previous symbols: [ "C14orf123" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHMP4A 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 | 13 | 14 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 1 | |||||
| Total | 0 | 0 | 14 | 1 | 0 |
Variants in CHMP4A
This is a list of pathogenic ClinVar variants found in the CHMP4A region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 14-24210422-T-C | not specified | Likely benign (Apr 19, 2023) | ||
| 14-24210431-T-C | not specified | Uncertain significance (Jun 07, 2024) | ||
| 14-24210455-A-G | not specified | Uncertain significance (Apr 12, 2022) | ||
| 14-24210479-T-G | not specified | Uncertain significance (Apr 20, 2023) | ||
| 14-24210664-T-G | not specified | Uncertain significance (Mar 27, 2023) | ||
| 14-24210685-C-T | not specified | Uncertain significance (Nov 18, 2022) | ||
| 14-24210730-G-A | not specified | Uncertain significance (Oct 20, 2023) | ||
| 14-24211433-T-C | not specified | Uncertain significance (Oct 10, 2023) | ||
| 14-24211455-C-T | not specified | Uncertain significance (May 17, 2023) | ||
| 14-24211505-C-G | not specified | Uncertain significance (Jan 17, 2024) | ||
| 14-24211574-C-T | not specified | Uncertain significance (Dec 20, 2023) | ||
| 14-24211773-C-G | not specified | Uncertain significance (May 23, 2023) | ||
| 14-24211827-T-G | not specified | Uncertain significance (Jan 25, 2023) | ||
| 14-24213424-T-C | not specified | Uncertain significance (Feb 28, 2024) | ||
| 14-24213520-C-T | not specified | Uncertain significance (Jul 14, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CHMP4A | protein_coding | protein_coding | ENST00000347519 | 6 | 4287 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 3.39e-9 | 0.0972 | 125311 | 3 | 433 | 125747 | 0.00174 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.699 | 123 | 147 | 0.838 | 0.00000740 | 1728 |
| Missense in Polyphen | 31 | 31.554 | 0.98244 | 429 | ||
| Synonymous | 0.585 | 53 | 58.7 | 0.903 | 0.00000301 | 503 |
| Loss of Function | -0.0107 | 13 | 13.0 | 1.00 | 5.49e-7 | 163 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00138 | 0.00137 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000491 | 0.000489 |
| Finnish | 0.000470 | 0.000462 |
| European (Non-Finnish) | 0.00241 | 0.00237 |
| Middle Eastern | 0.000491 | 0.000489 |
| South Asian | 0.00344 | 0.00340 |
| Other | 0.00131 | 0.00130 |
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). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. When overexpressed, membrane-assembled circular arrays of CHMP4A filaments can promote or stabilize negative curvature and outward budding. Via its interaction with PDCD6IP 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:12860994, ECO:0000269|PubMed:14505569, ECO:0000269|PubMed:14519844, ECO:0000269|PubMed:14583093, ECO:0000269|PubMed:18209100, ECO:0000269|PubMed:22660413}.;
- 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
- 0.0799
Intolerance Scores
- loftool
- 0.865
- rvis_EVS
- 0.26
- rvis_percentile_EVS
- 70.44
Haploinsufficiency Scores
- pHI
- 0.136
- hipred
- N
- hipred_score
- 0.477
- ghis
- 0.505
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.890
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Gene ontology
- Biological process
- posttranslational protein targeting to endoplasmic reticulum membrane;vesicle budding from membrane;nucleus organization;vacuolar transport;mitotic metaphase plate congression;membrane invagination;endosomal transport;macroautophagy;viral life cycle;multivesicular body assembly;viral budding via host ESCRT complex;protein polymerization;protein homooligomerization;midbody abscission;plasma membrane tubulation;negative regulation of neuron death;negative regulation of autophagosome assembly
- Cellular component
- ESCRT III complex;nucleus;cytoplasm;endosome;cytosol;plasma membrane;cytoplasmic side of plasma membrane;membrane coat;midbody;cytoplasmic vesicle membrane;late endosome membrane
- Molecular function
- protein binding;lipid binding;identical protein binding;protein homodimerization activity;ATPase binding