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

ENSG00000143546 ∙ NCBI:6279 ∙ OMIM:123885 ∙ HGNC:10498 ∙ Uniprot:P05109 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the S100A8 gene.

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			3			3
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	3	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: gnomAD

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: dbNSFP

• 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

• 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