SDCBP
protein-codingsyndecan binding protein, the group of PDZ domain containing
Gene summary
The protein encoded by this gene was initially identified as a molecule linking syndecan-mediated signaling to the cytoskeleton. The syntenin protein contains tandemly repeated PDZ domains that bind the cytoplasmic, C-terminal domains of a variety of transmembrane proteins. This protein may also affect cytoskeletal-membrane organization, cell adhesion, protein trafficking, and the activation of transcription factors. The protein is primarily localized to membrane-associated adherens junctions and focal adhesions but is also found at the endoplasmic reticulum and nucleus. Alternative splicing results in multiple transcript variants encoding different isoforms. Related pseudogenes have been identified on multiple chromosomes. [provided by RefSeq, Jan 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~29.9 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 SDCBP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005625.4. 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 | 2 | 2 | ||||
| missense | 29 | 3 | 32 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 32 | 3 | 0 | 35 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005616.2 | 8 | MANE Select | |
| Ensembl | ENSP00000260130.4 | 8 | MANE Select | |
| RefSeq | NP_001007068.1 | 8 | Standard | |
| RefSeq | NP_001007069.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
- miR-targeted genes in squamous cell - TarBase
- Ectoderm Differentiation
Biological Process
- negative regulation of receptor internalization
- protein targeting to membrane
- substrate-dependent cell migration, cell extension
- chemical synaptic transmission
- regulation of mitotic cell cycle
Molecular Function
- frizzled binding
- interleukin-5 receptor binding
- protein binding
- phosphatidylinositol-4,5-bisphosphate binding
- cytoskeletal adaptor activity
Cellular Component
- extracellular region
- extracellular space
- nucleus
- nucleoplasm
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000260130
- Coding exons
- 8
- Length
- 29937
- Individuals with no LoFs
- 125714
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 31
- Defined
- 125745
- p
- 0.000123
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.04 | 128 | 166 | 0.772 | 0.00000855 | 1962 |
| Missense (PolyPhen) | 20 | 38.962 | 0.51332 | 514 | ||
| Synonymous | 0.0259 | 53 | 53.2 | 0.995 | 0.00000268 | 580 |
| Loss of Function | 1.49 | 7 | 12.8 | 0.549 | 5.35e-7 | 172 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.00034 | 0.00026 | rare |
| Ashkenazi Jewish | 0.00025 | 0.00020 | rare |
| East Asian | 0.000059 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0.00011 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Multifunctional adapter protein involved in diverse array of functions including trafficking of transmembrane proteins, neuro and immunomodulation, exosome biogenesis, and tumorigenesis (PubMed:26291527). Positively regulates TGFB1- mediated SMAD2/3 activation and TGFB1-induced epithelial-to- mesenchymal transition (EMT) and cell migration in various cell types. May increase TGFB1 signaling by enhancing cell-surface expression of TGFR1 by preventing the interaction between TGFR1 and CAV1 and subsequent CAV1-dependent internalization and degradation of TGFR1 (PubMed:25893292). In concert with SDC1/4 and PDCD6IP, regulates exosome biogenesis (PubMed:22660413). Regulates migration, growth, proliferation, and cell cycle progression in a variety of cancer types (PubMed:26539120). In adherens junctions may function to couple syndecans to cytoskeletal proteins or signaling components. Seems to couple transcription factor SOX4 to the IL-5 receptor (IL5RA) (PubMed:11498591). May also play a role in vesicular trafficking (PubMed:11179419). Seems to be required for the targeting of TGFA to the cell surface in the early secretory pathway (PubMed:10230395). {ECO:0000269|PubMed:10230395, ECO:0000269|PubMed:11179419, ECO:0000269|PubMed:11498591, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:25893292, ECO:0000269|PubMed:26539120, ECO:0000303|PubMed:26291527}.;
Recessive Scores
- pRec
- 0.364
Intolerance Scores
- LoFtool
- 0.936
- RVIS EVS
- -0.52
- RVIS percentile EVS
- 21.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.903
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |