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

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]

Research

ResearchGenerating clinical summary…

Active trials

712

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.77

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in S100A8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 1,500

102 rare PASS variants

Rare truncating (LoF)

1 in 33,000

13 rare PASS variants

Rare synonymous (reference)

1 in 1,700

45 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for S100A8. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 1,700	1 in 31,000
South Asian	~43k	1 in 860	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 1,400	≈ 1 in 30,000
European (Finnish)	~27k	≈ 1 in 6,700	none seen
Admixed American	~22k	1 in 1,900	≈ 1 in 22,000
African / African American	~21k	1 in 1,200	none seen
East Asian	~20k	1 in 740	≈ 1 in 20,000
Ashkenazi Jewish	~13k	≈ 1 in 6,500	none seen
Middle Eastern	~2,884	≈ 1 in 960	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓