CHST14

CHST14, a protein-coding gene, encodes for the enzyme carbohydrate sulfotransferase 14 (CHST14)/ dermatan 4-O-sulfotransferase (D4ST1).

In humans, CHST14 is positioned on the long arm (q) of chromosome 15 at position 15.1, from base pair 40,470,961 to base pair 40,474,571. The CHST14 gene is 3,611 bases long, composed of 376 amino acids, and has a molecular mass of 42997 Da.

CHST14 is implicated in fetal development of connective tissues throughout multiple organ systems.{{cite journal | vauthors = Kosho T | title = CHST14/D4ST1 deficiency: New form of Ehlers-Danlos syndrome | journal = Pediatrics International | volume = 58 | issue = 2 | pages = 88–99 | date = February 2016 | pmid = 26646600 | doi = 10.1111/ped.12878 | s2cid = 5289682 }} It is also implicated in regulation of proliferation and neurogenesis of neural precursor cells.{{cite journal | vauthors = Bian S, Akyüz N, Bernreuther C, Loers G, Laczynska E, Jakovcevski I, Schachner M | title = Dermatan sulfotransferase Chst14/D4st1, but not chondroitin sulfotransferase Chst11/C4st1, regulates proliferation and neurogenesis of neural progenitor cells | journal = Journal of Cell Science | volume = 124 | issue = Pt 23 | pages = 4051–63 | date = December 2011 | pmid = 22159417 | doi = 10.1242/jcs.088120 | doi-access = free }} It has been linked to inhibition of peripheral nerve regeneration in adults.{{cite journal | vauthors = Akyüz N, Rost S, Mehanna A, Bian S, Loers G, Oezen I, Mishra B, Hoffmann K, Guseva D, Laczynska E, Irintchev A, Jakovcevski I, Schachner M | title = Dermatan 4-O-sulfotransferase1 ablation accelerates peripheral nerve regeneration | journal = Experimental Neurology | volume = 247 | pages = 517–30 | date = September 2013 | pmid = 23360803 | doi = 10.1016/j.expneurol.2013.01.025 | s2cid = 8093221 }}

Dermatan 4-O-sulfotransferase enzymatically transfers an active sulfate to position 4 of N-acetyl-D-galactosamine residues of dermatan sulfate, stabilizing this glycosaminoglycan.{{cite journal | vauthors = Miyake N, Kosho T, Mizumoto S, Furuichi T, Hatamochi A, Nagashima Y, Arai E, Takahashi K, Kawamura R, Wakui K, Takahashi J, Kato H, Yasui H, Ishida T, Ohashi H, Nishimura G, Shiina M, Saitsu H, Tsurusaki Y, Doi H, Fukushima Y, Ikegawa S, Yamada S, Sugahara K, Matsumoto N | display-authors = 6 | title = Loss-of-function mutations of CHST14 in a new type of Ehlers-Danlos syndrome | journal = Human Mutation | volume = 31 | issue = 8 | pages = 966–74 | date = August 2010 | pmid = 20533528 | doi = 10.1002/humu.21300 | s2cid = 46388905 | doi-access = free }} Dermatan sulfate is essential to extracellular matrix formation and is found in extensively in skin, tendons, cartilage, and the aortic wall.{{cite journal | vauthors = Penc SF, Pomahac B, Winkler T, Dorschner RA, Eriksson E, Herndon M, Gallo RL | title = Dermatan sulfate released after injury is a potent promoter of fibroblast growth factor-2 function | journal = The Journal of Biological Chemistry | volume = 273 | issue = 43 | pages = 28116–21 | date = October 1998 | pmid = 9774430 | doi = 10.1074/jbc.273.43.28116| doi-access = free }} Mutation of CHST14 results in a deficiency of dermatan sulfate, which disrupts glycosaminoglycan constituents in fibroblasts and impairs collagen fibril linkage within collagen bundles.

Mutation of CHST14 is associated with the Musculocontractural type of Ehlers–Danlos syndromes, recently specified as CHST14/D4ST1 deficiency. Previously, this condition has been independently referred to as adducted thumb-clubfoot syndrome,{{cite journal | vauthors = Dündar M, Müller T, Zhang Q, Pan J, Steinmann B, Vodopiutz J, Gruber R, Sonoda T, Krabichler B, Utermann G, Baenziger JU, Zhang L, Janecke AR | title = Loss of dermatan-4-sulfotransferase 1 function results in adducted thumb-clubfoot syndrome | journal = American Journal of Human Genetics | volume = 85 | issue = 6 | pages = 873–82 | date = December 2009 | pmid = 20004762 | pmc = 2790573 | doi = 10.1016/j.ajhg.2009.11.010 }} Ehlers-Danlos syndrome, Kosho type,{{cite journal | vauthors = Kosho T, Miyake N, Hatamochi A, Takahashi J, Kato H, Miyahara T, Igawa Y, Yasui H, Ishida T, Ono K, Kosuda T, Inoue A, Kohyama M, Hattori T, Ohashi H, Nishimura G, Kawamura R, Wakui K, Fukushima Y, Matsumoto N | display-authors = 6 | title = A new Ehlers-Danlos syndrome with craniofacial characteristics, multiple congenital contractures, progressive joint and skin laxity, and multisystem fragility-related manifestations | journal = American Journal of Medical Genetics. Part A | volume = 152A | issue = 6 | pages = 1333–46 | date = June 2010 | pmid = 20503305 | doi = 10.1002/ajmg.a.33498 | s2cid = 205312940 }} musculocontractural Ehlers-Danlos syndrome,{{cite journal | vauthors = Malfait F, Syx D, Vlummens P, Symoens S, Nampoothiri S, Hermanns-Lê T, Van Laer L, De Paepe A | title = Musculocontractural Ehlers-Danlos Syndrome (former EDS type VIB) and adducted thumb clubfoot syndrome (ATCS) represent a single clinical entity caused by mutations in the dermatan-4-sulfotransferase 1 encoding CHST14 gene | journal = Human Mutation | volume = 31 | issue = 11 | pages = 1233–9 | date = November 2010 | pmid = 20842734 | doi = 10.1002/humu.21355 | s2cid = 39702597 | url = https://hal.archives-ouvertes.fr/hal-00599478/document | doi-access = free }} and Ehlers-Danlos type VIB.{{cite journal | vauthors = Kosho T, Takahashi J, Ohashi H, Nishimura G, Kato H, Fukushima Y | title = Ehlers-Danlos syndrome type VIB with characteristic facies, decreased curvatures of the spinal column, and joint contractures in two unrelated girls | journal = American Journal of Medical Genetics. Part A | volume = 138A | issue = 3 | pages = 282–7 | date = October 2005 | pmid = 16158441 | doi = 10.1002/ajmg.a.30965 | s2cid = 37675709 }} Currently, 40 patients from 27 families have been diagnosed with this autosomal recessive mutation.{{cite journal | vauthors = Mizumoto S, Kosho T, Hatamochi A, Honda T, Yamaguchi T, Okamoto N, Miyake N, Yamada S, Sugahara K | title = Defect in dermatan sulfate in urine of patients with Ehlers-Danlos syndrome caused by a CHST14/D4ST1 deficiency | journal = Clinical Biochemistry | volume = 50| issue = 12| pages = 670–677 | date = February 2017 | pmid = 28238810 | doi = 10.1016/j.clinbiochem.2017.02.018 | hdl = 2115/68359 | hdl-access = free }} CHST14/D4ST1 deficiency is the first identified human disease that directly impacts dermatan sulfate production." Hallmark features include congenital malformations (extensive craniofacial defects, skin elasticity, joint laxity, multiple contractures) combined with progressive fragility of affected structures, with increased incidence of bruising, recurrent joint dislocations, pneumothorax, spinal degeneration, and other deformities.

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• {{UCSC gene info|CHST14}}

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• {{cite journal | vauthors = Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T | title = Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries | journal = DNA Research | volume = 12 | issue = 2 | pages = 117–26 | year = 2007 | pmid = 16303743 | doi = 10.1093/dnares/12.2.117 | doi-access = free }}
• {{cite journal | vauthors = Mikami T, Mizumoto S, Kago N, Kitagawa H, Sugahara K | title = Specificities of three distinct human chondroitin/dermatan N-acetylgalactosamine 4-O-sulfotransferases demonstrated using partially desulfated dermatan sulfate as an acceptor: implication of differential roles in dermatan sulfate biosynthesis | journal = The Journal of Biological Chemistry | volume = 278 | issue = 38 | pages = 36115–27 | date = September 2003 | pmid = 12847091 | doi = 10.1074/jbc.M306044200 | doi-access = free }}

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