S100A1
protein-codingS100 calcium binding protein A1, 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 may function in stimulation of Ca2+-induced Ca2+ release, inhibition of microtubule assembly, and inhibition of protein kinase C-mediated phosphorylation. Reduced expression of this protein has been implicated in cardiomyopathies. [provided by RefSeq, Jul 2008]
- S100A
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.1 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 S100A1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006271.2. 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 | 12 | 12 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 15 | 0 | 1 | 16 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006262.1 | 2 | MANE Select | |
| Ensembl | ENSP00000292169.2 | 2 | MANE Select | |
| Ensembl | ENSP00000357685.3 | 2 | Standard | |
| Ensembl | ENSP00000357687.3 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Toll-Like Receptors Cascades
- Innate Immune System
- Immune System
- Regulation of TLR by endogenous ligand
Biological Process
- negative regulation of transcription by RNA polymerase II
- toll-like receptor signaling pathway
- regulation of heart contraction
- substantia nigra development
- intracellular signal transduction
Molecular Function
- calcium ion binding
- protein binding
- identical protein binding
- protein homodimerization activity
- S100 protein binding
Cellular Component
- extracellular region
- nucleus
- sarcoplasmic reticulum
- Z disc
- M band
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000292169
- Coding exons
- 2
- Length
- 4112
- Individuals with no LoFs
- 125739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125747
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.155 | 57 | 53.8 | 1.06 | 0.00000296 | 624 |
| Missense (PolyPhen) | 24 | 18.699 | 1.2835 | 231 | ||
| Synonymous | -0.133 | 27 | 26.1 | 1.03 | 0.00000185 | 174 |
| Loss of Function | -0.0615 | 3 | 2.89 | 1.04 | 1.20e-7 | 41 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000035 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probably acts as a Ca(2+) signal transducer (PubMed:22399290). In response to an increase in intracellular Ca(2+) levels, binds calcium which triggers a conformational change (PubMed:23351007). This conformational change allows interaction of S1001A with specific target proteins, such as TPR- containing proteins, and the modulation of their activity (PubMed:22399290). {ECO:0000269|PubMed:22399290, ECO:0000269|PubMed:23351007}.;
Recessive Scores
- pRec
- 0.126
Intolerance Scores
- LoFtool
- 0.666
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 46.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.731
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |