S100A8

Chr 1

S100 calcium binding protein A8

Also known as: 60B8AG, CAGA, CFAG, CGLA, CP-10, L1Ag, MA387, MRP8

NCBI Gene: 6279 ENSG00000143546 UniProt: P05109 OMIM: 123885

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 may function in the inhibition of casein kinase and as a cytokine. Altered expression of this protein is associated with the disease cystic fibrosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.77

Clinical Summary— S100A8

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Population Constraint (gnomAD)

Low constraint (pLI 0.14) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

29 VUS of 43 total submissions

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Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.77LOEUF

pLI 0.138

Z-score 0.58

OE 0.54 (0.18–1.77)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.04Z-score

OE missense 0.98 (0.79–1.24)

51 obs / 51.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.54 (0.18–1.77)

0≤0.351.4

Missense OE?0.98 (0.79–1.24)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 1 / 1.9Missense obs/exp: 51 / 51.8Syn Z: -0.01

This gene — mechanism propensity

0.82top 10%

GOF

0.87top 5%

LOF

0.1994th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

43 submitted variants in ClinVar

ClinVar

Classification Summary

VUS29

Likely Benign8

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	29	0	29
Likely Benign	7	1	8
Benign	0	0	0
Total	36	1	37

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap S100A8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

S100A8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Fermented FoodInflammation

Comparing Effects of Fermented and Unfermented Pulses and Gut Microbiota

NOT YET RECRUITING

NCT06134076Phase NAPenn State UniversityStarted 2025-09

Unfermented chickpeaFermented chickpea

Crohn DiseaseNutrition AssessmentDiet Therapy

Comparison of Quality of Life During a Flare of Crohn's Disease Treated With Prednisolone or aCDED With PEN in Adult Patients

RECRUITING

NCT06953791Phase PHASE2University Hospital TuebingenStarted 2026-02-01

aCDED + ModulenPrednisolone

PreDiabetesDysbiosisEndotoxemia

Assessing Gut Microbiota Mediated Health Outcomes of Whole Wheat and Its Major Bioactive Components

ACTIVE NOT RECRUITING

NCT05318183Phase NAOhio State UniversityStarted 2022-01-27

Whole Wheat BreadWhite Bread (control)

Crohn Disease

Clinical, Imaging, and Endoscopic Outcomes of Children Newly Diagnosed With Crohn's Disease

RECRUITING

NCT05781152Phase PHASE4Connecticut Children's Medical CenterStarted 2023-06-10

Anti-TNF therapy

Healthy Children

To Investigate the Effects of Bifidobacterium Animalis Subsp. Lactis XLTG11 on Growth and Development, Incidence of Allergy and Immune Function in Infants

RECRUITING

NCT07490587Phase PHASE2Min-Tze LIONGStarted 2024-01-01

ProbioticPlacebo

Malnutrition (Calorie)Infant Nutrition DisorderGrowth Flatering

Goat Milk-Derived Formula vs. Undiluted Goat Milk in Infants Unable to Exclusively Breastfeed: Growth and Biomarker Analysis

RECRUITING

NCT07225153Phase NAAga Khan UniversityStarted 2025-08-30

GMDFAUndiluted Goat Milk

Adequate Vitamin C StatusInadequate Vitamin C Status

Anti-inflammatory Activities of Vitamin C Supplementation on the Gut Barrier Function in Adults With Obesity

RECRUITING

NCT07151105Phase NAOhio State UniversityStarted 2025-10-01