ANAPC4
protein-codinganaphase promoting complex subunit 4, the group of Anaphase promoting complex
Gene summary
A large protein complex, termed the anaphase-promoting complex (APC), or the cyclosome, promotes metaphase-anaphase transition by ubiquitinating its specific substrates such as mitotic cyclins and anaphase inhibitor, which are subsequently degraded by the 26S proteasome. Biochemical studies have shown that the vertebrate APC contains eight subunits. The composition of the APC is highly conserved in organisms from yeast to humans. The exact function of this gene product is not known. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~41.2 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 ANAPC4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_013367.3. 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 | 4 | 4 | ||||
| missense | 79 | 2 | 81 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 10 | 10 | ||||
| Total | 0 | 0 | 93 | 2 | 0 | 95 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_037499.2 | 28 | MANE Select | |
| Ensembl | ENSP00000318775.3 | 28 | MANE Select | |
| RefSeq | NP_001273685.1 | 28 | Standard | |
| Ensembl | ENSP00000426512.1 | 3 | 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)
- Progesterone-mediated oocyte maturation - 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
- ubiquitin-protein transferase activity
- protein binding
- protein phosphatase binding
Cellular Component
- nucleus
- nucleoplasm
- anaphase-promoting complex
- cytosol
- nuclear periphery
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000315368
- Coding exons
- 28
- Length
- 41286
- Individuals with no LoFs
- 125697
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 51
- Defined
- 125748
- p
- 0.000203
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.50 | 263 | 405 | 0.650 | 0.0000199 | 5288 |
| Missense (PolyPhen) | 49 | 115.8 | 0.42314 | 1547 | ||
| Synonymous | -0.0829 | 141 | 140 | 1.01 | 0.00000677 | 1455 |
| Loss of Function | 4.68 | 16 | 52.7 | 0.304 | 0.00000272 | 666 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000091 | 0.000087 | rare |
| Ashkenazi Jewish | 0.0017 | 0.0016 | notable |
| East Asian | 0.00061 | 0.00060 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0.00015 | 0.00013 | rare |
| Other | 0.00034 | 0.00033 | 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}.;
Recessive Scores
- pRec
- 0.125
Intolerance Scores
- LoFtool
- 0.578
- RVIS EVS
- -0.8
- RVIS percentile EVS
- 12.33
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.672
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |