HS2ST1

protein-coding

heparan sulfate 2-O-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. 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]

MANE transcript

NM_012262.4

Inheritance

ClinVar variants

P:6U:44B:11

Top phenotype

Neurofacioskeletal syndrome with or without renal agenesis

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr1:86,914,635-87,109,982

External References & Databases

Ensembl (ENSG00000153936)

Transcript & Mutation Effects

hg38 • Region Span ~195.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurofacioskeletal syndrome with or without renal agenesisLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030966

Submitter: Labcorp Genetics (formerly Invitae)

neurofacioskeletal syndrome with or without renal agenesisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030966

Submitter: G2P

neurofacioskeletal syndrome with or without renal agenesisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030966

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Neurofacioskeletal syndrome with or without renal agenesisAR

Manifestation: Craniofacial; Musculoskeletal; Ophthalmologic; Neurologic; Renal

Intervention: General

Rationale: 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

Refs: 33159882

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HS2ST1 variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 43

not providedTotal: 7

Neurofacioskeletal syndrome with or without renal agenesisTotal: 6

not specifiedTotal: 4

NEUROFACIOSKELETAL SYNDROME WITHOUT RENAL AGENESISTotal: 2

HS2ST1-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012262.4. 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				8 clinvar		8
missense	3 clinvar		42 clinvar	3 clinvar		48
nonsense	1 clinvar					1
start loss						0
frameshift	2 clinvar					2
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	6	0	44	11	0	61

Highest pathogenic variant AF is 0.000011879722

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012262.4	RefSeq	NP_036394.1	7	MANE Select
ENST00000370550.10	Ensembl	ENSP00000359581.4	7	MANE Select
NM_001134492.2	RefSeq	NP_001127964.1	5	Standard
ENST00000370551.8	Ensembl	ENSP00000359582.3	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
hs2st1a	Danio rerio	Structure: blastoderm cell Quality: increased size abnormal

Gene / Model

Organism

Observed Phenotype

hs2st1a

Danio rerio

Structure: blastoderm cell

Quality: increased size

abnormal

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, polysaccharide chain biosynthetic process
heparan sulfate proteoglycan biosynthetic process, enzymatic modification

Molecular Function

heparan sulfate 2-O-sulfotransferase activity
sulfotransferase activity

Cellular Component

Golgi membrane
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370550
Coding exons: 7
Length: 222004
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125741
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.51	135	194	0.695	0.0000100	2349
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.142

Intolerance Scores

LoFtool: 0.251
RVIS EVS: -0.01
RVIS percentile EVS: 53.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.517

Gene Damage Prediction

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