HS2ST1

Chr 1AR

heparan sulfate 2-O-sulfotransferase 1

Also known as: 2-OST, NFSRA, dJ604K5.2

NCBI Gene: 9653 ENSG00000153936 UniProt: Q7LGA3 OMIM: 604844

HS2ST1 encodes heparan sulfate 2-O-sulfotransferase 1, which catalyzes the transfer of sulfate groups to the 2-OH position of iduronic acid or glucuronic acid residues within heparan sulfate chains during biosynthesis. Biallelic mutations cause neurofacioskeletal syndrome with or without renal agenesis, an autosomal recessive disorder affecting the nervous system, skeletal development, and kidney formation. The gene shows significant constraint against loss-of-function variants (LOEUF 0.465), consistent with its essential role in development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biologic activities. This gene encodes a member of the heparan sulfate biosynthetic enzyme family that transfers sulfate to the 2 position of the iduronic acid residue of heparan sulfate. The disruption of this gene resulted in no kidney formation in knockout embryonic mice, indicating that the absence of this enzyme may interfere with the signaling required for kidney formation. Two alternatively spliced transcript variants that encode different proteins have been found for this gene. [provided by RefSeq, Aug 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurofacioskeletal syndrome with or without renal agenesisMIM #619194

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.47

LOEUF

LOF

Mechanism· G2P