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Last update 08 May 2025

HS6ST1

Last update 08 May 2025

Basic Info

Synonyms

heparan sulfate 6-O-sulfotransferase 1, Heparan-sulfate 6-O-sulfotransferase 1, HS6ST

+ [2]

Introduction

6-O-sulfation enzyme which catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to position 6 of the N-sulfoglucosamine residue (GlcNS) of heparan sulfate. Critical for normal neuronal development where it may play a role in neuron branching. May also play a role in limb development. May prefer iduronic acid.

Drugs associated with HS6ST1

ZP-2571

Target

HS6ST1

Mechanism

HS6ST1 inhibitors

Active Org.-

Originator Org.

Zacharon Pharmaceuticals, Inc.

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with HS6ST1

100 Translational Medicine associated with HS6ST1

0 Patents (Medical) associated with HS6ST1

135

Literatures (Medical) associated with HS6ST1

04 Dec 2024·Essays in biochemistry

Genetic variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfate diversity.

Review

Author: Baranger, Kévin ; Ouidja, Mohand Ouidir ; De Lichy, Aubert ; De Las Rivas, Javier ; Merrick, Heloise ; Cormier-Daire, Valerie ; Rebergue, Nicolas ; Le Douaron, Gael ; González-Velasco, Oscar ; Maïza, Auriane ; Laffray, Xavier ; Gomez-Henao, Wilton ; Papy-Garcia, Dulce ; Fernig, David G ; Chantepie, Sandrine ; Biard, Denis S F ; Barreto, Guillermo ; Dady, Alwyn ; Huynh, Minh Bao ; Rubio, Karla

Heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans (PG) consist of a core protein to which the glycosaminoglycan (GAG) chains, HS or CS, are attached through a common linker tetrasaccharide. In the extracellular space, they are involved in the regulation of cell communication, assuring development and homeostasis. The HSPG biosynthetic pathway has documented 51 genes, with many diseases associated to defects in some of them. The phenotypic consequences of this genetic variation in humans, and of genetic ablation in mice, and their expression patterns, led to a phenotypically centered HSPG biosynthetic pathway model. In this model, HS sequences produced by ubiquitous NDST1, HS2ST and HS6ST enzymes are essential for normal development and homeostasis, whereas tissue restricted HS sequences produced by the non-ubiquitous NDST2-4, HS6ST2-3, and HS3ST1-6 enzymes are involved in adaptative behaviors, cognition, tissue responsiveness to stimuli, and vulnerability to disease. The model indicates that the flux through the HSPG/CSPG pathways and its diverse branches is regulated by substrate preferences and protein-protein-interactions. This results in a privileged biosynthesis of HSPG over that of CSPGs, explaining the phenotypes of linkeropathies, disease caused by defects in genes involved in the biosynthesis of the common tetrasaccharide linker. Documented feedback loops whereby cells regulate HS sulfation, and hence the interactions of HS with protein partners, may be similarly implemented, e.g., protein tyrosine sulfation and other posttranslational modifications in enzymes of the HSPG pathway. Together, ubiquitous HS, specialized HS, and their biosynthesis model can facilitate research for a better understanding of HSPG roles in physiology and pathology.

01 Aug 2024·Molecular and Cellular Endocrinology

Prevalence of pathogenic variants and digenic disease in patients diagnosed with normosmic hypogonadotropic hypogonadism/Kallmann Syndrome

Article

Author: Chorich, Lynn ; Dougherty, Michael P ; Kim, Hyung-Goo ; Layman, Lawrence C ; Kim, Soo-Hyun ; Roman, Robert A ; Poch, Alexandra ; Hawkins, Zoe

BACKGROUNDHypogonadotropic hypogonadism (HH) is due to impaired gonadotropin releasing hormone (GnRH) action resulting in absent puberty and infertility. At least 44 genes have been identified to possess genetic variants in 40-50% of nHH/KS, and 2-20% have presumed digenic disease, but not all variants have been characterized in vitro.HYPOTHESISThe prevalence of pathogenic (P)/likely pathogenic (LP) variants in monogenic and digenic nHH/KS is lower than reported.DESIGNCross-sectional study.SETTINGUniversity Research Laboratory.SUBJECTS158 patients with nHH/KS.METHODSExome sequencing (ES) was performed and variants were filtered for 44 known genes using Varsome and confirmed by Sanger Sequencing.MAIN OUTCOME MEASURESP/LP variants in nHH/KS genes.RESULTSES resulted in >370,000 variants, from which variants in 44 genes were filtered. Thirty-one confirmed P/LP variants in 10 genes (ANOS1, CHD7, DUSP6, FGFR1, HS6ST1, KISS1, PROKR2, SEMA3A, SEMA3E, TACR3), sufficient to cause disease, were identified in 30/158 (19%) patients. Only 2/158 (1.2%) patients had digenic variant combinations: a male with hemizygous ANOS1 and heterozygous TACR3 variants and a male with heterozygous SEMA3A and SEMA3E variants. Two patients (1.2%) had compound heterozygous GNRHR (autosomal recessive) variants-one P and one variant of uncertain significance (VUS). Five patients (3.2%) had heterozygous P/LP variants in either GNRHR or TACR3 (both autosomal recessive), but no second variant.CONCLUSIONOur prevalence of P/LP variants in nHH/KS was 19%, and digenicity was observed in 1.2%. These findings are less than those previously reported, and probably represent a more accurate estimation since VUS are not included.

29 May 2024·Cardiovascular Research

Four-week inhibition of the renin–angiotensin system in spontaneously hypertensive rats results in persistently lower blood pressure with reduced kidney renin and changes in expression of relevant gene networks

Article

Author: Balding, David ; De Vries, Nathan ; Charchar, Fadi ; Maier, Michelle C ; Wilkinson-Berka, Jennifer L ; Byars, Sean G ; Allen, Andrew M ; Suphapimol, Varaporn ; Prestes, Priscilla R ; Melo, Mariana ; Samani, Nilesh ; Takeuchi, Fumihiko ; Harrap, Stephen B ; Kato, Norihiro

AbstractAimsPrevention of human hypertension is an important challenge and has been achieved in experimental models. Brief treatment with renin–angiotensin system (RAS) inhibitors permanently reduces the genetic hypertension of the spontaneously hypertensive rat (SHR). The kidney is involved in this fascinating phenomenon, but relevant changes in gene expression are unknown.Methods and resultsIn SHR, we studied the effect of treatment between 10 and 14 weeks of age with the angiotensin receptor blocker, losartan, or the angiotensin-converting enzyme inhibitor, perindopril [with controls for non-specific effects of lowering blood pressure (BP)], on differential RNA expression, DNA methylation, and renin immunolabelling in the kidney at 20 weeks of age. RNA sequencing revealed a six-fold increase in renin gene (Ren) expression during losartan treatment (P < 0.0001). Six weeks after losartan, arterial pressure remained lower (P = 0.006), yet kidney Ren showed reduced expression by 23% after losartan (P = 0.03) and by 43% after perindopril (P = 1.4 × 10−6) associated with increased DNA methylation (P = 0.04). Immunolabelling confirmed reduced cortical renin after earlier RAS blockade (P = 0.002). RNA sequencing identified differential expression of mRNAs, miRNAs, and lncRNAs with evidence of networking and co-regulation. These included 13 candidate genes (Grhl1, Ammecr1l, Hs6st1, Nfil3, Fam221a, Lmo4, Adamts1, Cish, Hif3a, Bcl6, Rad54l2, Adap1, Dok4), the miRNA miR-145-3p, and the lncRNA AC115371. Gene ontogeny analyses revealed that these networks were enriched with genes relevant to BP, RAS, and the kidneys.ConclusionEarly RAS inhibition in SHR resets genetic pathways and networks resulting in a legacy of reduced Ren expression and BP persisting for a minimum of 6 weeks.

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HS6ST1

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