S100A4
protein-codingS100 calcium binding protein A4, the group of S100 calcium binding proteins|EF-hand domain containing
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 motility, invasion, and tubulin polymerization. Chromosomal rearrangements and altered expression of this gene have been implicated in tumor metastasis. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]
- MTS1
- CAPL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.5 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 S100A4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002961.3. 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 | 4 | 4 | ||||
| missense | 8 | 8 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 12 | 0 | 4 | 16 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002952.1 | 2 | MANE Select | |
| Ensembl | ENSP00000357705.4 | 2 | MANE Select | |
| RefSeq | NP_062427.1 | 2 | Standard | |
| Ensembl | ENSP00000346294.4 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vitamin D Receptor Pathway
Biological Process
- epithelial to mesenchymal transition
- positive regulation of I-kappaB kinase/NF-kappaB signaling
Molecular Function
- RNA binding
- actin binding
- calcium ion binding
- protein binding
- identical protein binding
Cellular Component
- extracellular region
- extracellular space
- nucleus
- neuron projection
- perinuclear region of cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368716
- Coding exons
- 2
- Length
- 6524
- Individuals with no LoFs
- 125706
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 41
- Defined
- 125747
- p
- 0.000163
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.365 | 48 | 55.7 | 0.862 | 0.00000288 | 682 |
| Missense (PolyPhen) | 13 | 15.532 | 0.837 | 215 | ||
| Synonymous | 0.699 | 19 | 23.3 | 0.816 | 0.00000137 | 171 |
| Loss of Function | -0.0357 | 3 | 2.93 | 1.02 | 1.22e-7 | 43 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00026 | 0.00025 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.520
Intolerance Scores
- LoFtool
- 0.817
- RVIS EVS
- -0.19
- RVIS percentile EVS
- 39.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.815
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |