Table 3.
Biosynthetic enzymes of CS and DS chains.
| Enzymes (activity) |
Coding genes (synonym) |
Chromosomal location | mRNA accession number | MIM number | Human genetic disorders | Clinical features | References for the human diseases | References for the knockout mice |
|---|---|---|---|---|---|---|---|---|
|
Chondroitin synthase (GalNAcT-II, CS-GlcAT-II) |
CHSY1 | 15q26.3 | NM_014918 | 605282 608183 |
Temtamy preaxial brachydactyly syndrome Syndromic recessive preaxial brachydactyly Neuropathy | Short stature, limb malformation, hearing loss. | [77–80] | [81] |
|
CHSY2
(CHSY3, CSS3) |
5q23.3 | NM_175856 | 609963 | — | — | — | — | |
|
CHSY3
(CHPF2, CSGLCA-T) |
7q36.1 | NM_019015 | 608037 | — | — | — | — | |
|
| ||||||||
| Chondroitin-polymerizing factor (GalNAcT-II, CS-GlcAT-II) |
CHPF
(CSS2) |
2q35 | NM_024536 | 610405 | — | — | — | [81, 82] |
|
| ||||||||
| Chondroitin N-acetylgalactosaminyltransferase (GalNAcT-I, GalNAcT-II) |
CSGALNACT1 | 8p21.3 | NM_018371 | — | Hereditary motor and sensory neuropathy Unknown type Bell's palsy |
Intermittent postural tremor, reduction in compound muscle action potentials, acquired idiopathic generalized anhidrosis, hemifacial palsy. | [83] | [81, 84–86] |
| CSGALNACT2 | 10q11.21 | NM_018590 | — | — | — | — | [86] | |
|
| ||||||||
| Dermatan sulfate epimerase | DSE | 6q22 | NM_013352 | 615539 605942 |
Ehlers-Danlos syndrome musculocontractural type 2 | Characteristic facial features, congenital contractures of the thumbs and the feet, hypermobility of finger, elbow, and knee joints, atrophic scarring of the skin, and myopathy. | [87] | [88, 89] |
| DSEL | 18q22.1 | NM_032160 | 611125 | Bipolar disorder Depressive disorder Diaphragmatic hernia Microphthalmia |
Alternating episodes of depression and mania or hypomania, and congenital malformation of the diaphragm. | [90–92] | [93] | |
|
| ||||||||
| Uranyl 2-O-sulfotransferase | UST | 6q25.1 | NM_005715 | 610752 | — | — | — | — |
|
| ||||||||
| Chondroitin 4-O-sulfotransferase |
CHST11
(C4ST-1) |
12q | NM_018413 | 610128 | — | — | — | [94–96] |
|
CHST12
(C4ST-2) |
7p22 | NM_018641 | 610129 | — | — | — | — | |
|
CHST13
(C4ST-3) |
3q21.3 | NM_152889 | 610124 | — | — | — | — | |
|
| ||||||||
| Dermatan 4-O-sulfotransferase |
CHST14
(D4ST-1) |
15q15.1 | NM_130468 | 601776 608429 |
Ehlers-Danlos syndrome musculocontractural type 1 Adducted thumb-clubfoot syndrome |
Craniofacial dysmorphism, multiple contractures, progressive joint and skin laxities, multisystem fragility-related manifestations, contractures of thumbs and feet, defects of heart, kidney and intestine. | [97–106] | [96, 107] |
|
| ||||||||
| Chondroitin 6-O-sulfotransferase |
CHST3
(C6ST-1) |
10q22.1 | NM_004273 | 143095 603799 |
Spondyloepiphyseal dysplasia with congenital joint dislocations Spondyloepiphyseal dysplasia Omani type Chondrodysplasia with multiple dislocations Humerospinal dysostosis Larsen syndrome autosomal recessive type Desbuquois syndrome |
Short stature, severe kyphoscoliosis, osteoarthritis (elbow, wrist and knee), secondary dislocation of large joints, rhizomelia, fusion of carpal bones, mild brachydactyly, metacarpal shortening, ventricular septal defect, mitral and tricuspid defects, aortic regurgitations, deafness. | [108–113] | [114–116] |
|
| ||||||||
|
N-Acetylgalactosamine-4-sulfate- 6-O-sulfotransferase |
CHST15
(GalNAc4S-6ST) |
10q26 | NM_015892 | 608277 | — | — | — | [117] |
—: not reported.
CSS: chondroitin sulfate synthase; DSEL: dermatan sulfate epimerase-like; CHST: carbohydrate sulfotransferase.