S100A12
protein-codingS100 calcium binding protein A12, the group of EF-hand domain containing|S100 calcium binding proteins
Gene summary
The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein is proposed to be involved in specific calcium-dependent signal transduction pathways and its regulatory effect on cytoskeletal components may modulate various neutrophil activities. The protein includes an antimicrobial peptide which has antibacterial activity. [provided by RefSeq, Nov 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.9 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 S100A12 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005621.2. 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 | 1 | ||||
| missense | 17 | 2 | 19 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 17 | 2 | 1 | 20 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005612.1 | 2 | MANE Select | |
| Ensembl | ENSP00000357726.3 | 2 | MANE Select | |
| Ensembl | ENSP00000761162.1 | 2 | Standard | |
| Ensembl | ENSP00000761163.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Toll Like Receptor 7/8 (TLR7/8) Cascade
- Neutrophil degranulation
- Signaling by Interleukins
- Cytokine Signaling in Immune system
- Toll Like Receptor 9 (TLR9) Cascade
Biological Process
- monocyte chemotaxis
- xenobiotic metabolic process
- inflammatory response
- neutrophil chemotaxis
- killing of cells of other organism
Molecular Function
- copper ion binding
- calcium ion binding
- protein binding
- zinc ion binding
- RAGE receptor binding
Cellular Component
- extracellular region
- nucleus
- cytoplasm
- cytosol
- cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368737
- Coding exons
- 2
- Length
- 1942
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.580 | 60 | 48.6 | 1.23 | 0.00000235 | 611 |
| Missense (PolyPhen) | 20 | 12.774 | 1.5657 | 190 | ||
| Synonymous | -1.28 | 27 | 19.7 | 1.37 | 0.00000100 | 174 |
| Loss of Function | 1.24 | 0 | 1.78 | 0.00 | 7.45e-8 | 23 |
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 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: S100A12 is a calcium-, zinc- and copper-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. Its proinflammatory activity involves recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to receptor for advanced glycation endproducts (AGER). Binding to AGER activates the MAP-kinase and NF-kappa-B signaling pathways leading to production of proinflammatory cytokines and up-regulation of cell adhesion molecules ICAM1 and VCAM1. Acts as a monocyte and mast cell chemoattractant. Can stimulate mast cell degranulation and activation which generates chemokines, histamine and cytokines inducing further leukocyte recruitment to the sites of inflammation. Can inhibit the activity of matrix metalloproteinases; MMP2, MMP3 and MMP9 by chelating Zn(2+) from their active sites. Possesses filariacidal and filariastatic activity. Calcitermin possesses antifungal activity against C.albicans and is also active against E.coli and P.aeruginosa but not L.monocytogenes and S.aureus. {ECO:0000269|PubMed:11522286, ECO:0000269|PubMed:17208591, ECO:0000269|PubMed:18292089, ECO:0000269|PubMed:19386136}.;
Recessive Scores
- pRec
- 0.113
Intolerance Scores
- LoFtool
- 0.450
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.04
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.00651
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |