Table 1.
Proteins discussed in this review that are associated to human genetic diseases
| Gene | Protein | LoF Molecular Phenotype | Human Genetic Disease | OMIM Ref. |
|---|---|---|---|---|
| P3H1 | Prolyl 3-hydroxylase 1 | Low 3-hydroxylation of Pro986 of COL1A1; excess lysyl hydroxylation and glycosylation of helical domain; delayed collagen folding | Osteogenesis imperfecta type VIII | 610339 |
| P3H2 | Prolyl 3-hydroxylase 2 | Loss of 3-hydroxyproline at sites on collagen I, II, and IV in the eye | High myopia and other eye defects; basement membrane nephropathy | 610341 |
| P3H3 | Prolyl 3-hydroxylase 3 | Under hydroxylation of Lys at collagen triple-helical domain cross-linking sites; reduced thermal stability of skin collagen; altered collagen fibril diameters | None known but some phenotypic similarities to Kyphoscoliotic Ehlers-Danlos syndrome | 610342 |
| P4HA1 | Prolyl 4-hydroxylase subunit α 1 | Reduced prolyl 4-hydroxylase activity; reduced collagen thermal stability; loss of basement membrane organization | Possible roles in congenital disease of connective tissue | 176710 |
| P4HA2 | Prolyl 4-hydroxylase subunit α 2 | Reduced 4-hydroxyproline content of collagens; minor reduction in thermal stability (collagen II) | Autosomal dominant myopia 25 | 600608 |
| P4HB/PDIA1 | Prolyl 4-hydroxylase subunit β | Mutations in a′ domain affect PDI activity; reduced oxidoreductase activity | Cole-Carpenter syndrome-1 | 176790 |
| PLOD1 | Lysine hydroxylase 1/Procollagen-lysine, 2-oxoglutarate 5-dioxygenase | Reduced lysyl hydroxylase activity; reduced hydroxylysine content of collagens; altered collagen fibril morphology | Kyphoscoliotic Ehlers-Danlos syndrome | 153454 |
| PLOD2 | Lysine hydroxylase 2 | Loss of hydroxylation of telopeptide lysines of collagen I; reduced trivalent collagen I cross linking | Bruck syndrome 2 | 601865 |
| PLOD3 | Lysine hydroxylase 3 | Loss of glycosyltransferase activity on galactosyl hydroxylysine residues in collagens or other extracellular proteins with a collagenous domain; defective basement membrane structure | Bone fragility with contractures, arterial rupture, and deafness | 603066 |
| B3GLCT | β-1,3-glucosyltransferase | Reduced glucosyltransferase activity to O-fucosylated serine or threonine in specific motifs of TSR domains; reduced secretion of cognate TSR proteins | Peters-plus syndrome | 610308 |
| FAM20C | Family with sequence similarity 20, member C | Reduced phosphorylation of FAM20C substrates; reduced activity of chondroitin 4-O-sulfotransferase-1; reduced FAMC20 secretion | Raine syndrome | 611061 |
See OMIM entries for further details. GGT, glucosyltransferase; LoF, loss of function; OMIM, Online Mendelian Inheritance in Man (https://www.ncbi.nlm.nih.gov/omim/); TSR, thrombospondin type 1 repeated domain.