CALCOCO2
protein-codingcalcium binding and coiled-coil domain 2
Gene summary
This gene encodes a coiled-coil domain-containing protein. The encoded protein functions as a receptor for ubiquitin-coated bacteria and plays an important role in innate immunity by mediating macroautophagy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~37.2 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 CALCOCO2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005831.5. 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 | 0 | |||||
| missense | 51 | 4 | 55 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 57 | 4 | 0 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005822.1 | 12 | MANE Select | |
| Ensembl | ENSP00000258947.3 | 12 | MANE Select | |
| RefSeq | NP_001248319.1 | 13 | Standard | |
| RefSeq | NP_001248320.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Mitophagy - animal - Homo sapiens (human)
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
- EGFR1
Biological Process
- viral process
- response to interferon-gamma
- xenophagy
- positive regulation of autophagosome maturation
Molecular Function
- protein binding
- protein homodimerization activity
Cellular Component
- autophagosome membrane
- nucleus
- cytoplasm
- autophagosome
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000448105
- Coding exons
- 13
- Length
- 35535
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 32
- Defined
- 125745
- p
- 0.000127
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.913 | 197 | 237 | 0.833 | 0.0000113 | 3161 |
| Missense (PolyPhen) | 48 | 66.117 | 0.72599 | 946 | ||
| Synonymous | 0.638 | 76 | 83.4 | 0.911 | 0.00000413 | 751 |
| Loss of Function | 3.03 | 12 | 29.9 | 0.401 | 0.00000133 | 372 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00062 | 0.00062 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Xenophagy-specific receptor required for autophagy- mediated intracellular bacteria degradation. Acts as an effector protein of galectin-sensed membrane damage that restricts the proliferation of infecting pathogens such as Salmonella typhimurium upon entry into the cytosol by targeting LGALS8- associated bacteria for autophagy (PubMed:22246324). Initially orchestrates bacteria targeting to autophagosomes and subsequently ensures pathogen degradation by regulating pathogen-containing autophagosome maturation (PubMed:23022382, PubMed:25771791). Bacteria targeting to autophagosomes relies on its interaction with MAP1LC3A, MAP1LC3B and/or GABARAPL2, whereas regulation of pathogen-containing autophagosome maturation requires the interaction with MAP3LC3C (PubMed:23022382, PubMed:25771791). May play a role in ruffle formation and actin cytoskeleton organization and seems to negatively regulate constitutive secretion (PubMed:17635994). {ECO:0000269|PubMed:17635994, ECO:0000269|PubMed:22246324, ECO:0000269|PubMed:23022382, ECO:0000269|PubMed:23386746, ECO:0000269|PubMed:25771791}.;
Recessive Scores
- pRec
- 0.0584
Intolerance Scores
- LoFtool
- 0.818
- RVIS EVS
- 0.62
- RVIS percentile EVS
- 83.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.734
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |