SCUBE3 Gene
Signal Peptide, CUB Domain, and EGF-like Domain-Containing Protein 3
Gene Information Card
| Symbol | SCUBE3 |
|---|---|
| Full Name | Signal Peptide, CUB Domain And EGF Like Domain Containing 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 6p21.31 |
| NCBI Gene ID | 222663 ncbi.nlm.nih.gov/gene/222663 |
| Ensembl ID | ENSG00000146192 |
| UniProt ID | Q8IX30 |
| OMIM ID | 614708 |
| HGNC ID | 15985 |
| Aliases | C6orf97, MGC131914 |
Description
SCUBE3 encodes a secreted glycoprotein belonging to the SCUBE (Signal peptide, CUB domain, and EGF-like domain) family. The protein contains an N-terminal signal peptide, multiple EGF-like repeats, a CUB domain, and a C-terminal cysteine-rich domain. SCUBE3 functions as a co-receptor or modulator of bone morphogenetic protein (BMP) signaling, particularly BMP2 and BMP4, and is involved in developmental processes including tooth formation, craniofacial morphogenesis, and angiogenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Tooth agenesis, selective, 7 (STHAG7) | Loss-of-function mutations in SCUBE3 impair BMP signaling during odontogenesis, leading to failure of tooth development. | OMIM #618500; PMID: 31981491 |
| Craniofacial abnormalities | SCUBE3 variants disrupt BMP-mediated craniofacial development, resulting in facial dysmorphism. | PMID: 31981491 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.3 | Medium |
| Lung | 8.7 | Low |
| Kidney | 6.5 | Low |
| Testis | 15.2 | Medium |
| Thyroid | 10.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (umbilical vein endothelial) | 18.4 | High expression |
| HEK 293 | 9.2 | Moderate |
| A549 (lung carcinoma) | 5.6 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1054C>T (p.Arg352*) | Nonsense | Rare | Loss of function; associated with tooth agenesis |
| c.1462G>A (p.Gly488Arg) | Missense | Rare | Likely damaging; disrupts EGF-like domain |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or disrupt the CUB domain impair BMP signaling and cause tooth agenesis.
Gain of Function (GOF)
Not reported for SCUBE3.
Dominant Negative (DN)
Not reported for SCUBE3.
View complete mutation data：
Gene Ontology (GO)
| • BMP signaling pathway | • extracellular region |
| • calcium ion binding | • growth factor activity |
| • cell differentiation |
Pathways
• BMP signaling pathway (Reactome: R-HSA-201451)
• TGF-beta signaling pathway
Protein Summary
SCUBE3 is a secreted glycoprotein of approximately 993 amino acids. It contains an N-terminal signal peptide, nine EGF-like repeats, a CUB domain, and a C-terminal cysteine-rich domain. The protein is expressed in various tissues, including heart, lung, kidney, testis, and thyroid, and is particularly abundant in endothelial cells. SCUBE3 modulates BMP signaling by interacting with BMP ligands and their receptors, thereby regulating developmental processes such as tooth formation and craniofacial development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SCUBE3 Knockout HEK293 Cell Line | EDJ-KQ3009 | Human | 222663 | Details Get a Quote |
| SCUBE3 Knockout HeLa Cell Line | EDJ-KQ59197 | Human | 222663 | Details Get a Quote |
| SCUBE3 Knockout A-549 Cell Line | EDJ-KQ67665 | Human | 222663 | Details Get a Quote |
| SCUBE3 Knockout HCT 116 Cell Line | EDJ-KQ76052 | Human | 222663 | Details Get a Quote |
