ANAPC5
protein-codinganaphase promoting complex subunit 5, the group of Anaphase promoting complex
Gene summary
This gene encodes a tetratricopeptide repeat-containing component of the anaphase promoting complex/cyclosome (APC/C), a large E3 ubiquitin ligase that controls cell cycle progression by targeting a number of cell cycle regulators such as B-type cyclins for 26S proteasome-mediated degradation through ubiquitination. The encoded protein is required for the proper ubiquitination function of APC/C and for the interaction of APC/C with transcription coactivators. It also interacts with polyA binding protein and represses internal ribosome entry site-mediated translation. Multiple transcript variants encoding different isoforms have been found for this gene. These differences cause translation initiation at a downstream AUG and result in a shorter protein (isoform b), compared to isoform a. [provided by RefSeq, Nov 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~91.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0005090
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ANAPC5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016237.5. 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 | 2 | 1 | 3 | |||
| missense | 53 | 3 | 56 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 9 | 9 | ||||
| Total | 0 | 0 | 64 | 4 | 0 | 68 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057321.2 | 17 | MANE Select | |
| Ensembl | ENSP00000261819.3 | 17 | MANE Select | |
| RefSeq | NP_001131031.1 | 15 | Standard | |
| RefSeq | NP_001317418.1 | 17 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell cycle - Homo sapiens (human)
- Oocyte meiosis - Homo sapiens (human)
- Ubiquitin mediated proteolysis - Homo sapiens (human)
- HTLV-I infection - Homo sapiens (human)
- IL-17 signaling pathway - Homo sapiens (human)
Biological Process
- cell cycle
- anaphase-promoting complex-dependent catabolic process
- positive regulation of mitotic metaphase/anaphase transition
- cell division
- protein K11-linked ubiquitination
Molecular Function
- protein phosphatase binding
- ubiquitin protein ligase activity
Cellular Component
- nucleus
- nucleoplasm
- anaphase-promoting complex
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261819
- Coding exons
- 17
- Length
- 91652
- Individuals with no LoFs
- 125662
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 86
- Defined
- 125748
- p
- 0.000342
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.30 | 291 | 424 | 0.686 | 0.0000234 | 4966 |
| Missense (PolyPhen) | 81 | 132.09 | 0.6132 | 1493 | ||
| Synonymous | 0.309 | 169 | 174 | 0.970 | 0.0000106 | 1429 |
| Loss of Function | 2.79 | 21 | 40.1 | 0.524 | 0.00000188 | 483 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00018 | 0.00017 | rare |
| Ashkenazi Jewish | 0.00071 | 0.00069 | rare |
| East Asian | 0.00044 | 0.00044 | rare |
| Finnish | 0.00051 | 0.00051 | rare |
| European (Non-Finnish) | 0.00033 | 0.00033 | rare |
| South Asian | 0.00040 | 0.00039 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. {ECO:0000269|PubMed:18485873}.;
Intolerance Scores
- LoFtool
- 0.342
- RVIS EVS
- -0.55
- RVIS percentile EVS
- 19.8
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.926
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |