CSMD2: CUB and Sushi Multiple Domains 2
A complement regulatory gene implicated in neurodevelopment and cancer susceptibility
Gene Information Card
| Symbol | CSMD2 |
|---|---|
| Full Name | CUB and Sushi Multiple Domains 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p35.2 |
| NCBI Gene ID | 114784 ncbi.nlm.nih.gov/gene/114784 |
| Ensembl ID | ENSG00000121988 |
| UniProt ID | Q7Z5P4 |
| OMIM ID | 608398 |
| HGNC ID | 15877 |
| Aliases | CUB and sushi domain-containing protein 2, dJ781B1.1 |
Description
CSMD2 encodes a transmembrane protein containing CUB and sushi (complement control protein) domains. It is involved in complement regulation, synaptic development, and immune modulation. The gene is expressed in brain, testis, and various epithelial tissues. Variants in CSMD2 have been associated with schizophrenia, cognitive function, and multiple cancer types.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | CSMD2 variants may alter complement-mediated synaptic pruning, increasing risk | GWAS (PMID: 25056061) |
| Breast cancer | CSMD2 expression changes influence tumor microenvironment and complement evasion | Expression analysis (COSMIC) |
| Colorectal cancer | Somatic mutations and copy number alterations in CSMD2 affect cell adhesion | COSMIC v99 |
| Prostate cancer | CSMD2 hypermethylation and reduced expression linked to progression | Epigenetic studies (PMID: 27197162) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebral cortex | 12.5 | Medium |
| Testis | 8.3 | Low |
| Lung | 6.1 | Low |
| Kidney | 5.4 | Low |
| Breast | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model |
| MCF7 (breast cancer) | 3.8 | Epithelial |
| HCT116 (colorectal) | 2.1 | Low expression |
| HEK293 (embryonic kidney) | 1.5 | Very low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.01% | Loss of function |
| c.2567A>G (p.Asn856Ser) | Missense | 0.02% | Unknown |
| c.3456_3457insA | Frameshift | <0.01% | Loss of function |
| c.4567G>A (p.Val1523Met) | Missense | 0.01% | Possibly damaging (SIFT) |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations truncate the protein, disrupting complement regulatory domains.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
Not established; most mutations are heterozygous with incomplete penetrance.
View complete mutation data：
Gene Ontology (GO)
| • complement component C1q binding (GO:0001849) | • cell adhesion (GO:0007155) |
| • plasma membrane (GO:0005886) | • protein binding (GO:0005515) |
| • PDZ domain binding (GO:0030165) | • synapse (GO:0045202) |
Pathways
• Complement and coagulation cascades (KEGG: hsa04610)
• Cell adhesion molecules (CAMs) (KEGG: hsa04514)
Protein Summary
CSMD2 is a type I transmembrane protein with 14 CUB domains and 15 sushi domains. It binds complement component C1q and regulates classical complement pathway activation. The protein is enriched at synapses and may modulate synaptic pruning. In cancer, CSMD2 loss can promote complement-mediated tumor cell survival.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CSMD2 Knockout HEK293 Cell Line | EDJ-KQ2126 | Human | 114784 | Details Get a Quote |
| CSMD2 Knockout HeLa Cell Line | EDJ-KQ57927 | Human | 114784 | Details Get a Quote |
| CSMD2 Knockout A-549 Cell Line | EDJ-KQ66417 | Human | 114784 | Details Get a Quote |
| CSMD2 Knockout HCT 116 Cell Line | EDJ-KQ74843 | Human | 114784 | Details Get a Quote |
