FAM20C: The Golgi Casein Kinase and Regulator of Biomineralization
A comprehensive biomedical overview of FAM20C, a secreted kinase with critical roles in phosphorylation, bone development, and disease.
Gene Information Card
| Symbol | FAM20C |
|---|---|
| Full Name | FAM20C, golgi associated secretory pathway kinase |
| Gene Type | Protein coding |
| Chromosomal Location | 7p22.3 |
| NCBI Gene ID | 56975 ncbi.nlm.nih.gov/gene/56975 |
| Ensembl ID | ENSG00000142409 |
| UniProt ID | Q8IXL6 |
| OMIM ID | 611061 |
| HGNC ID | 22140 |
| Aliases | DMP4, GEF-CK, DMP-4 |
Description
The FAM20C gene encodes a protein kinase localized to the Golgi apparatus. It is a member of the family with sequence similarity 20 (FAM20) and is also known as Golgi casein kinase (GEF-CK). FAM20C is a secreted kinase that phosphorylates a wide range of extracellular proteins, particularly those containing the S-x-E/pS motif. It plays a critical role in biomineralization by phosphorylating matrix proteins in bone and dentin, and it regulates phosphate metabolism by controlling the activity of fibroblast growth factor 23 (FGF23). Mutations in this gene are a primary cause of Raine syndrome, a severe osteosclerotic bone disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Raine Syndrome | Biallelic loss-of-function mutations in FAM20C lead to a complete loss of kinase activity, disrupting the phosphorylation of key bone matrix proteins (e.g., SPP1, DMP1) and FGF23. This results in severe defects in bone mineralization, osteosclerosis, and often lethal neonatal presentations. | OMIM #259660; ClinVar; PMID: 17632515 |
| Hypophosphatemic Osteomalacia | Specific mutations in FAM20C can impair the phosphorylation of FGF23, leading to its increased cleavage and inactivation. Reduced active FGF23 levels cause renal phosphate wasting, leading to hypophosphatemia and osteomalacia (softening of bones). | PMID: 28601602; PMID: 29323644 |
| Amelogenesis Imperfecta | FAM20C is essential for proper enamel formation. Mutations can lead to enamel hypomineralization and hypoplasia, presenting as a dental phenotype often seen in patients with Raine syndrome or as an isolated trait. | PMID: 23981287; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone | Not available | High |
| Kidney | Not available | High |
| Liver | Not available | Medium |
| Lung | Not available | Medium |
| Brain | Not available | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Osteoblasts | Not available | Key site of expression for biomineralization |
| Odontoblasts | Not available | Essential for dentin formation |
| Hepatocytes | Not available | Source of circulating FAM20C |
| Proximal Tubule Cells | Not available | Expression in kidney related to FGF23 regulation |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg408Trp | Missense | Rare | Loss-of-function; associated with Raine syndrome |
| p.Gly279Arg | Missense | Rare | Loss-of-function; associated with Raine syndrome |
| p.Pro328Leu | Missense | Rare | Loss-of-function; associated with Raine syndrome |
| c.1366C>T (p.Arg456*) | Nonsense | Rare | Loss-of-function; premature truncation, associated with Raine syndrome |
Mutation functional classification
Loss of Function (LOF)
The vast majority of disease-causing FAM20C mutations are loss-of-function. They result in reduced or absent kinase activity, leading to hypophosphorylation of substrates like FGF23 and bone matrix proteins. This is the primary mechanism for Raine syndrome and related bone and phosphate disorders.
Gain of Function (GOF)
No clear gain-of-function mutations have been identified or characterized for FAM20C in human disease. The gene is not a known oncogene, and its role in cancer is not well-established.
Dominant Negative (DN)
While most cases of Raine syndrome are autosomal recessive, some heterozygous missense mutations may exert a dominant-negative effect by dimerizing with the wild-type protein and impairing its overall function, though this is less common than recessive loss-of-function.
View complete mutation data：
Gene Ontology (GO)
| • Golgi apparatus | • protein serine/threonine kinase activity |
| • ATP binding | • phosphorylation |
| • biomineralization | • extracellular matrix organization |
| • regulation of osteoblast differentiation | • peptidyl-serine phosphorylation |
| • peptidyl-threonine phosphorylation | • secretion |
Pathways
• Biomineralization
• FGF23 signaling and phosphate regulation
• Protein phosphorylation in the secretory pathway
Protein Summary
The FAM20C protein is a 601-amino-acid Golgi-associated kinase. It is synthesized as a precursor with a signal peptide and is localized to the Golgi lumen where it phosphorylates secreted proteins. It is the primary kinase responsible for the phosphorylation of the S-x-E/pS motif found in many extracellular matrix proteins. Its substrates include osteopontin (SPP1), dentin matrix protein 1 (DMP1), and FGF23. By phosphorylating FGF23, it promotes its secretion in an intact, active form. In bone, it is crucial for the proper mineralization of the extracellular matrix. The protein structure includes a conserved kinase domain and a unique N-terminal region that may be involved in substrate recognition.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FAM20C Knockout HEK293 Cell Line | EDJ-KQ51545 | Human | 56975 | Details Get a Quote |
| FAM20C Knockout HeLa Cell Line | EDJ-KQ56781 | Human | 56975 | Details Get a Quote |
| FAM20C Knockout A-549 Cell Line | EDJ-KQ65284 | Human | 56975 | Details Get a Quote |
| FAM20C Knockout HCT 116 Cell Line | EDJ-KQ73727 | Human | 56975 | Details Get a Quote |
