GCA
protein-codinggrancalcin, the group of EF-hand domain containing
Gene summary
This gene encodes a calcium-binding protein that is abundant in neutrophils and macrophages. In the absence of divalent cation, this protein localizes to the cytosolic fraction; with magnesium alone, it partitions with the granule fraction; and in the presence of magnesium and calcium, it associates with both the granule and membrane fractions. Alternative splicing and use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Aug 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~52.8 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 GCA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012198.5. 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 | 7 | 1 | 8 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 10 | 1 | 0 | 11 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036330.1 | 8 | MANE Select | |
| Ensembl | ENSP00000394842.2 | 8 | MANE Select | |
| RefSeq | NP_001317194.1 | 8 | Standard | |
| RefSeq | NP_001317195.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neutrophil degranulation
- Innate Immune System
- Immune System
Biological Process
- neutrophil degranulation
- membrane fusion
Molecular Function
- calcium ion binding
- protein binding
- protein homodimerization activity
- protein heterodimerization activity
Cellular Component
- extracellular region
- cytoplasm
- cytosol
- plasma membrane
- azurophil granule lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000437150
- Coding exons
- 8
- Length
- 52756
- Individuals with no LoFs
- 124910
- Homozygous LoFs
- 6
- Heterozygous LoFs
- 832
- Defined
- 125748
- p
- 0.00334
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.00810 | 119 | 119 | 1.00 | 0.00000589 | 1424 |
| Missense (PolyPhen) | 23 | 32.281 | 0.71249 | 415 | ||
| Synonymous | -1.23 | 48 | 38.3 | 1.25 | 0.00000196 | 387 |
| Loss of Function | 1.37 | 8 | 13.4 | 0.595 | 6.65e-7 | 164 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00087 | 0.00086 | rare |
| Latino/Admixed American | 0.0021 | 0.0021 | notable |
| Ashkenazi Jewish | 0.0011 | 0.0011 | notable |
| East Asian | 0.0070 | 0.0061 | notable |
| Finnish | 0.016 | 0.016 | notable |
| European (Non-Finnish) | 0.0022 | 0.0021 | notable |
| South Asian | 0.00079 | 0.00072 | rare |
| Other | 0.0030 | 0.0029 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Calcium-binding protein that may play a role in the adhesion of neutrophils to fibronectin. May play a role in the formation of focal adhesions.;
Recessive Scores
- pRec
- 0.183
Intolerance Scores
- LoFtool
- 0.703
- RVIS EVS
- 0.53
- RVIS percentile EVS
- 80.58
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.266
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |