S100A8
S100 calcium binding protein A8, the group of S100 calcium binding proteins|EF-hand domain containing
Basic information
Region (hg38): 1:153390031-153391073
Previous symbols: [ "CAGA", "CFAG" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the S100A8 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 2 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 2 | 0 | 0 |
Variants in S100A8
This is a list of pathogenic ClinVar variants found in the S100A8 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-153390168-T-A | not specified | Uncertain significance (Nov 08, 2021) | ||
| 1-153390234-C-T | not specified | Uncertain significance (Nov 10, 2021) | ||
| 1-153390418-T-C | not specified | Uncertain significance (Dec 20, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| S100A8 | protein_coding | protein_coding | ENST00000368733 | 2 | 1157 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.138 | 0.639 | 125671 | 0 | 1 | 125672 | 0.00000398 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.0401 | 51 | 51.8 | 0.984 | 0.00000272 | 626 |
| Missense in Polyphen | 12 | 15.795 | 0.75972 | 206 | ||
| Synonymous | -0.0138 | 23 | 22.9 | 1.00 | 0.00000149 | 159 |
| Loss of Function | 0.582 | 1 | 1.86 | 0.539 | 7.74e-8 | 25 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000880 | 0.00000880 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: S100A8 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis and adhesion. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH- oxidase by facilitating the enzyme complex assembly at the cell membrane, transferring arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve proinflammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory activity includes 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 pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF- kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread. The iNOS-S100A8/A9 transnitrosylase complex directs selective inflammatory stimulus-dependent S-nitrosylation of GAPDH and probably multiple targets such as ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif; S100A8 seems to contribute to S-nitrosylation site selectivity. {ECO:0000269|PubMed:12626582, ECO:0000269|PubMed:15331440, ECO:0000269|PubMed:15598812, ECO:0000269|PubMed:15642721, ECO:0000269|PubMed:16258195, ECO:0000269|PubMed:19087201, ECO:0000269|PubMed:19122197, ECO:0000269|PubMed:19935772, ECO:0000269|PubMed:21487906, ECO:0000269|PubMed:22363402, ECO:0000269|PubMed:22808130, ECO:0000269|PubMed:25417112}.;
- Pathway
- IL-17 signaling pathway - Homo sapiens (human);Vitamin D Receptor Pathway;Neutrophil degranulation;Toll-Like Receptors Cascades;Antimicrobial peptides;Innate Immune System;Immune System;Regulation of TLR by endogenous ligand;Endogenous TLR signaling;Metal sequestration by antimicrobial proteins
(Consensus)
Recessive Scores
- pRec
- 0.455
Intolerance Scores
- loftool
- rvis_EVS
- 0.04
- rvis_percentile_EVS
- 56.25
Haploinsufficiency Scores
- pHI
- 0.290
- hipred
- N
- hipred_score
- 0.146
- ghis
- 0.519
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.898
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Low | Low | Low |
Mouse Genome Informatics
- Gene name
- S100a8
- Phenotype
- embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Gene ontology
- Biological process
- cytokine production;toll-like receptor signaling pathway;leukocyte migration involved in inflammatory response;acute inflammatory response;chronic inflammatory response;positive regulation of peptide secretion;autophagy;apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;inflammatory response;response to zinc ion;astrocyte development;peptidyl-cysteine S-nitrosylation;antimicrobial humoral response;positive regulation of cell growth;neutrophil chemotaxis;sequestering of zinc ion;response to lipopolysaccharide;chemokine production;wound healing;defense response to bacterium;neutrophil degranulation;innate immune response;response to ethanol;positive regulation of inflammatory response;defense response to fungus;positive regulation of NF-kappaB transcription factor activity;regulation of cytoskeleton organization;neutrophil aggregation;positive regulation of intrinsic apoptotic signaling pathway
- Cellular component
- extracellular region;extracellular space;nucleus;cytosol;cytoskeleton;plasma membrane;secretory granule lumen;intermediate filament cytoskeleton;collagen-containing extracellular matrix;extracellular exosome
- Molecular function
- calcium ion binding;protein binding;microtubule binding;zinc ion binding;Toll-like receptor 4 binding;arachidonic acid binding;RAGE receptor binding