CHMP1A
protein-codingcharged multivesicular body protein 1A, the group of Charged multivesicular body proteins|ESCRT-III associated factors
Gene summary
This gene encodes a member of the CHMP/Chmp family of proteins which are involved in multivesicular body sorting of proteins to the interiors of lysosomes. The initial prediction of the protein sequence encoded by this gene suggested that the encoded protein was a metallopeptidase. The nomenclature has been updated recently to reflect the correct biological function of this encoded protein. Several transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]
- PRSM1
- PCOLN3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013990
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0013990
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0013990
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CHMP1A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002768.5. 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 | 19 | 37 | 1 | 58 | |
| missense | 1 | 43 | 8 | 52 | ||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 2 | 4 | 6 | |||
| Total | 2 | 6 | 66 | 45 | 1 | 120 |
Highest pathogenic variant AF is 0.0000477211
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002759.2 | 7 | MANE Select | |
| Ensembl | ENSP00000380998.3 | 7 | MANE Select | |
| RefSeq | NP_001076783.1 | 6 | Standard | |
| Ensembl | ENSP00000442120.3 | 7 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| chmp1a | Danio rerio | Structure: molecular layer valvula cerebelli Quality: decreased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- Necroptosis - Homo sapiens (human)
Biological Process
- proteolysis
- nucleus organization
- mitotic chromosome condensation
- mitotic metaphase plate congression
- regulation of centrosome duplication
Molecular Function
- protein binding
- metallopeptidase activity
- zinc ion binding
- protein domain specific binding
- identical protein binding
Cellular Component
- condensed nuclear chromosome
- ESCRT III complex
- early endosome
- multivesicular body
- microtubule organizing center
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000397901
- Coding exons
- 7
- Length
- 13415
- Individuals with no LoFs
- 124635
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 124645
- p
- 0.0000401
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.760 | 102 | 126 | 0.810 | 0.00000794 | 1274 |
| Missense (PolyPhen) | 23 | 43.846 | 0.52456 | 460 | ||
| Synonymous | -1.31 | 70 | 57.4 | 1.22 | 0.00000426 | 365 |
| Loss of Function | 1.16 | 7 | 11.2 | 0.627 | 4.75e-7 | 129 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00017 | 0.00017 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00017 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probable peripherally associated 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. Involved in cytokinesis. Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells. May also be involved in chromosome condensation. Targets the Polycomb group (PcG) protein BMI1/PCGF4 to regions of condensed chromatin. May play a role in stable cell cycle progression and in PcG gene silencing. {ECO:0000269|PubMed:11559747, ECO:0000269|PubMed:11559748, ECO:0000269|PubMed:19129479, ECO:0000269|PubMed:23045692}.;
- Disease
- DISEASE: Pontocerebellar hypoplasia 8 (PCH8) [MIM:614961]: An autosomal recessive neurodevelopmental disorder characterized by severe psychomotor retardation, abnormal movements, hypotonia, spasticity, and variable visual defects. Brain MRI shows pontocerebellar hypoplasia, decreased cerebral white matter, and a thin corpus callosum. {ECO:0000269|PubMed:23023333}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Intolerance Scores
- LoFtool
- 0.233
- RVIS EVS
- 0.15
- RVIS percentile EVS
- 64.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.149
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |