Carbohydrate sulfotransferase 14 is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

that in humans is encoded by the ''CHST14''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Gene

''CHST14,'' a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

-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 Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 102 million base pairs (the building material of DNA) and represents between 3% and 3.5% of the total DNA ...

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.

Ontology

''CHST14'' is implicated in

fetal development Prenatal development () includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal devel ...

connective tissues Connective tissue is one of the four primary types of animal tissue (biology), tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Con ...

throughout multiple organ systems. It is also implicated in regulation of proliferation and

neurogenesis Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). It occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells (NECs) ...

of neural precursor cells. It has been linked to inhibition of

peripheral nerve A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system. A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...

regeneration in adults.

Function

Dermatan 4-O-sulfotransferase enzymatically transfers an active

sulfate The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ar ...

to position 4 of N-acetyl-D-galactosamine residues of

dermatan sulfate Dermatan sulfate is a glycosaminoglycan (formerly called a mucopolysaccharide) found mostly in skin, but also in blood vessels, heart valves, tendons, and lungs. It is also referred to as chondroitin sulfate B, although it is no longer classifie ...

, stabilizing this

glycosaminoglycan Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case ...

. Dermatan sulfate is essential to

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...

formation and is found in extensively in skin, tendons, cartilage, and the aortic wall.

Mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

of ''CHST14'' results in a deficiency of dermatan sulfate, which disrupts glycosaminoglycan constituents in

fibroblasts A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells o ...

and impairs collagen fibril linkage within

collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

bundles.

Clinical significance

of ''CHST14'' is associated with the Musculocontractural type of

Ehlers–Danlos syndromes Ehlers–Danlos syndromes (EDS) are a group of 13 genetic connective-tissue disorders in the current classification, with the latest type discovered in 2018. Symptoms include loose joints, joint pain, stretchy velvety skin, and abnormal scar fo ...

, recently specified as CHST14/D4ST1 deficiency. Previously, this condition has been independently referred to as adducted thumb-clubfoot syndrome, Ehlers-Danlos syndrome, Kosho type, musculocontractural Ehlers-Danlos syndrome, and Ehlers-Danlos type VIB. Currently, 40 patients from 27 families have been diagnosed with this

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

mutation. CHST14/D4ST1 deficiency is the first identified human disease that directly impacts dermatan sulfate production." Hallmark features include

congenital malformations A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can r ...

(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 A pneumothorax is an abnormal collection of air in the pleural space between the lung and the chest wall. Symptoms typically include sudden onset of sharp, one-sided chest pain and shortness of breath. In a minority of cases, a one-way valve ...

, spinal degeneration, and other deformities.

Gene

Ontology

Function

Clinical significance

References

External links

Further reading