HS2ST1

heparan sulfate 2-O-sulfotransferase 1, the group of Sulfotransferases, membrane bound

Basic information

Region (hg38): 1:86914635-87109982

Links

ENSG00000153936 ∙ NCBI:9653 ∙ OMIM:604844 ∙ HGNC:5193 ∙ Uniprot:Q7LGA3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurofacioskeletal syndrome with or without renal agenesis (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurofacioskeletal syndrome with or without renal agenesis	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Ophthalmologic; Neurologic; Renal	33159882

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HS2ST1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HS2ST1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4		4
missense			18	3		21
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	0	0	18	7	1

Variants in HS2ST1

This is a list of pathogenic ClinVar variants found in the HS2ST1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-86915043-C-T		Inborn genetic diseases	Uncertain significance (Feb 03, 2022)
1-86915046-C-T		Inborn genetic diseases	Uncertain significance (Feb 22, 2023)
1-86915095-TCGC-GAA		Neurofacioskeletal syndrome with or without renal agenesis	Pathogenic (Feb 18, 2021)
1-86915129-CCAGAAA-C		Neurofacioskeletal syndrome with or without renal agenesis	Likely pathogenic (Dec 02, 2024)
1-87072984-A-G		Inborn genetic diseases	Uncertain significance (Jul 09, 2021)
1-87072997-G-A		Inborn genetic diseases	Uncertain significance (Sep 17, 2021)
1-87073003-A-G		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
1-87073006-C-T		Inborn genetic diseases • HS2ST1-related disorder	Likely benign (Jan 03, 2022)
1-87073040-T-C			Likely benign (Jan 01, 2024)
1-87073060-C-T		Neurofacioskeletal syndrome with or without renal agenesis	Uncertain significance (-)
1-87073117-A-G		Inborn genetic diseases	Uncertain significance (Dec 16, 2022)
1-87073135-C-T		Inborn genetic diseases	Uncertain significance (Feb 10, 2022)
1-87073150-CA-C		NEUROFACIOSKELETAL SYNDROME WITHOUT RENAL AGENESIS	Pathogenic (Feb 18, 2021)
1-87084175-A-G		Neurofacioskeletal syndrome with or without renal agenesis	Benign (Apr 11, 2023)
1-87084186-C-T		Neurofacioskeletal syndrome with or without renal agenesis	Benign (Sep 01, 2024)
1-87084198-G-A		Inborn genetic diseases	Uncertain significance (Dec 28, 2022)
1-87084206-A-G		Inborn genetic diseases	Uncertain significance (Oct 09, 2024)
1-87084236-C-G		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
1-87084239-G-A		Inborn genetic diseases	Uncertain significance (Jan 08, 2024)
1-87084257-G-A		Inborn genetic diseases	Likely benign (Aug 02, 2021)
1-87092559-A-G		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
1-87092574-G-T		Neurofacioskeletal syndrome with or without renal agenesis	Pathogenic (Feb 18, 2021)
1-87092608-T-C		NEUROFACIOSKELETAL SYNDROME WITHOUT RENAL AGENESIS	Pathogenic (Feb 18, 2021)
1-87092648-A-C		Neurofacioskeletal syndrome with or without renal agenesis	Pathogenic (Feb 18, 2021)
1-87097906-G-A			Likely benign (Feb 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HS2ST1	protein_coding	protein_coding	ENST00000370550	7	222004

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.545	0.455	125733	0	8	125741	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.51	135	194	0.695	0.0000100	2349
Missense in Polyphen		28	62.293	0.44949		788
Synonymous	0.946	61	71.2	0.857	0.00000367	639
Loss of Function	3.27	4	19.7	0.203	0.00000116	226

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.000102	0.0000992
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000358	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the transfer of sulfate to the C2-position of selected hexuronic acid residues within the maturing heparan sulfate (HS). 2-O-sulfation within HS, particularly of iduronate residues, is essential for HS to participate in a variety of high- affinity ligand-binding interactions and signaling processes. Mediates 2-O-sulfation of both L-iduronyl and D-glucuronyl residues (By similarity). {ECO:0000250}.
• Pathway: 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;Glycosaminoglycan metabolism;heparan sulfate biosynthesis (late stages);heparan sulfate biosynthesis;Metabolism (Consensus)

Recessive Scores

• pRec: 0.142

Intolerance Scores

• loftool: 0.251
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.51

Haploinsufficiency Scores

• pHI: 0.854
• hipred: N
• hipred_score: 0.302
• ghis: 0.622

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.517

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hs2st1
• Phenotype: pigmentation phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; renal/urinary system phenotype; skeleton phenotype; vision/eye phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: hs2st1a
• Affected structure: blastoderm cell
• Phenotype tag: abnormal
• Phenotype quality: increased size

Gene ontology

• Biological process: glycosaminoglycan biosynthetic process;heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process;heparan sulfate proteoglycan biosynthetic process, enzymatic modification
• Cellular component: Golgi membrane;membrane;integral component of membrane
• Molecular function: heparan sulfate 2-O-sulfotransferase activity;sulfotransferase activity