CHMP4A
protein-codingcharged multivesicular body protein 4A, the group of Charged multivesicular body proteins|ESCRT-III
Gene summary
CHMP4A 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]).[supplied by OMIM, Mar 2008]
- C14orf123
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CHMP4A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014169.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 31 | 1 | 32 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 36 | 2 | 0 | 38 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_054888.3 | 6 | MANE Select | |
| Ensembl | ENSP00000324205.11 | 6 | MANE Select | |
| Ensembl | ENSP00000449757.2 | 4 | Standard | |
| Ensembl | ENSP00000432575.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- Necroptosis - Homo sapiens (human)
- Disease
- Vesicle-mediated transport
- Membrane Trafficking
Biological Process
- posttranslational protein targeting to endoplasmic reticulum membrane
- vesicle budding from membrane
- nucleus organization
- vacuolar transport
- mitotic metaphase plate congression
Molecular Function
- protein binding
- lipid binding
- identical protein binding
- protein homodimerization activity
- ATPase binding
Cellular Component
- ESCRT III complex
- nucleus
- cytoplasm
- endosome
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000347519
- Coding exons
- 6
- Length
- 4287
- Individuals with no LoFs
- 125311
- Homozygous LoFs
- 3
- Heterozygous LoFs
- 433
- Defined
- 125747
- p
- 0.00174
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.699 | 123 | 147 | 0.838 | 0.00000740 | 1728 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00062 | 0.00062 | rare |
| Latino/Admixed American | 0.00075 | 0.00075 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00049 | 0.00049 | rare |
| Finnish | 0.00047 | 0.00046 | rare |
| European (Non-Finnish) | 0.0024 | 0.0024 | notable |
| South Asian | 0.0034 | 0.0034 | notable |
| Other | 0.0013 | 0.0013 | notable |
dbNSFP Gene Annotations
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}.;
Recessive Scores
- pRec
- 0.0799
Intolerance Scores
- LoFtool
- 0.865
- RVIS EVS
- 0.26
- RVIS percentile EVS
- 70.44
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.890
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |