SDC4
protein-codingsyndecan 4, the group of Syndecans
Gene summary
The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan that functions as a receptor in intracellular signaling. The encoded protein is found as a homodimer and is a member of the syndecan proteoglycan family. This gene is found on chromosome 20, while a pseudogene has been found on chromosome 22. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~23.1 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 SDC4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002999.4. 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 | 0 | |||||
| missense | 26 | 1 | 27 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 27 | 1 | 0 | 28 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002990.2 | 5 | MANE Select | |
| Ensembl | ENSP00000361818.3 | 5 | MANE Select | |
| Ensembl | ENSP00000571764.1 | 5 | Standard | |
| Ensembl | ENSP00000571764.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sdc4 | Danio rerio | Structure: CaP motoneuron Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell adhesion molecules (CAMs) - Homo sapiens (human)
- ECM-receptor interaction - Homo sapiens (human)
- Fluid shear stress and atherosclerosis - Homo sapiens (human)
- Proteoglycans in cancer - Homo sapiens (human)
- Signaling by GPCR
Biological Process
- retinoid metabolic process
- ureteric bud development
- neural tube closure
- glycosaminoglycan biosynthetic process
- glycosaminoglycan catabolic process
Molecular Function
- fibronectin binding
- protein kinase C binding
- protein binding
- identical protein binding
- thrombospondin receptor activity
Cellular Component
- Golgi lumen
- plasma membrane
- integral component of plasma membrane
- focal adhesion
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000372733
- Coding exons
- 5
- Length
- 23137
- Individuals with no LoFs
- 125729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 19
- Defined
- 125748
- p
- 0.0000756
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.117 | 118 | 114 | 1.03 | 0.00000624 | 1271 |
| Missense (PolyPhen) | 39 | 40.43 | 0.96463 | 491 | ||
| Synonymous | 0.0942 | 49 | 49.8 | 0.983 | 0.00000301 | 399 |
| Loss of Function | 1.30 | 5 | 9.29 | 0.538 | 5.66e-7 | 100 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cell surface proteoglycan that bears heparan sulfate. Regulates exosome biogenesis in concert with SDCBP and PDCD6IP (PubMed:22660413). {ECO:0000269|PubMed:22660413}.;
Recessive Scores
- pRec
- 0.207
Intolerance Scores
- LoFtool
- 0.572
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 41.64
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.861
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |