HS3ST1

protein-coding

heparan sulfate-glucosamine 3-sulfotransferase 1, the group of Sulfotransferases, membrane bound

Gene summary

Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biologic activities. The enzyme encoded by this gene is a member of the heparan sulfate biosynthetic enzyme family. It possesses both heparan sulfate glucosaminyl 3-O-sulfotransferase activity, anticoagulant heparan sulfate conversion activity, and is a rate limiting enzyme for synthesis of anticoagulant heparan. This enzyme is an intraluminal Golgi resident protein. [provided by RefSeq, Jul 2008]

MANE transcript

NM_005114.4

Inheritance

—

ClinVar variants

U:50B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.53

Max pathogenic AF

—

Genomic locus

chr4:11,393,150-11,429,564

External References & Databases

Ensembl (ENSG00000002587)

Transcript & Mutation Effects

hg38 • Region Span ~36.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HS3ST1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 51

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005114.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			50 clinvar	1 clinvar		51
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	50	1	0	51

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005114.4	RefSeq	NP_005105.1	1	MANE Select
ENST00000002596.6	Ensembl	ENSP00000002596.5	1	MANE Select
ENST00000510712.1	Ensembl	ENSP00000422629.1	1	Standard
ENST00000514690.5	Ensembl	ENSP00000425673.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glycosaminoglycan biosynthesis - heparan sulfate / heparin - Homo sapiens (human)
Metapathway biotransformation Phase I and II
Metabolism of carbohydrates
HS-GAG biosynthesis
Heparan sulfate/heparin (HS-GAG) metabolism

Biological Process

glycosaminoglycan biosynthetic process
heparan sulfate proteoglycan biosynthetic process

Molecular Function

sulfotransferase activity
[heparan sulfate]-glucosamine 3-sulfotransferase 1 activity
heparan sulfate sulfotransferase activity

Cellular Component

Golgi lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000002596
Coding exons: 1
Length: 36616
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125748
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.09	171	216	0.792	0.0000156	2008
Missense (PolyPhen)		52	96.177	0.54067		868
Synonymous	0.599	96	104	0.925	0.00000823	621
Loss of Function	1.34	5	9.44	0.529	5.74e-7	90

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to position 3 of glucosamine residues in heparan. Catalyzes the rate limiting step in the biosynthesis of heparan sulfate (HSact). This modification is a crucial step in the biosynthesis of anticoagulant heparan sulfate as it completes the structure of the antithrombin pentasaccharide binding site. {ECO:0000269|PubMed:9346953}.;

Recessive Scores

pRec: 0.132

Intolerance Scores

RVIS EVS: -0.43
RVIS percentile EVS: 25.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.341

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium