HS6ST2

heparan sulfate 6-O-sulfotransferase 2, the group of Sulfotransferases, membrane bound

Basic information

Region (hg38): X:132626015-132961395

Links

ENSG00000171004 ∙ NCBI:90161 ∙ OMIM:300545 ∙ HGNC:19133 ∙ Uniprot:Q96MM7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Paganini-Miozzo syndrome (Limited), mode of inheritance: XL
• Paganini-Miozzo syndrome (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mental retardation, X-linked, syndromic, Paganini-Miozzo type	XL	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; Neurologic; Ophthalmologic	30471091

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HS6ST2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HS6ST2 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				5	1	6
missense			42	4	3	49
nonsense			1			1
start loss						0
frameshift					1	1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	43	9	5

Variants in HS6ST2

This is a list of pathogenic ClinVar variants found in the HS6ST2 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-132628283-C-T			Likely benign (May 01, 2020)
X-132628308-G-A		Paganini-Miozzo syndrome	Likely benign (Aug 10, 2021)
X-132628317-C-T		not specified	Uncertain significance (May 09, 2023)
X-132628318-G-A		not specified	Uncertain significance (Jan 23, 2023)
X-132628373-G-C		not specified	Uncertain significance (Sep 30, 2021)
X-132628419-G-A		not specified	Uncertain significance (Jul 11, 2023)
X-132628437-T-C			Uncertain significance (Feb 01, 2020)
X-132628469-C-G		not specified	Uncertain significance (Aug 17, 2021)
X-132628480-G-T		not specified	Uncertain significance (Jul 05, 2023)
X-132628495-C-T		HS6ST2-related disorder	Uncertain significance (Nov 08, 2023)
X-132628513-C-A		HS6ST2-related disorder	Likely benign (Dec 16, 2019)
X-132628521-T-G		not specified	Uncertain significance (Aug 13, 2021)
X-132628542-T-C			Uncertain significance (May 01, 2024)
X-132628586-C-A		not specified	Uncertain significance (Dec 15, 2022)
X-132628623-A-G		not specified	Uncertain significance (Jan 17, 2024)
X-132628630-C-T		HS6ST2-related disorder	Benign (Apr 30, 2024)
X-132628680-G-A			Uncertain significance (Dec 01, 2019)
X-132628755-G-A			Uncertain significance (Apr 01, 2023)
X-132628822-C-G		not specified	Conflicting classifications of pathogenicity (Nov 01, 2023)
X-132628830-T-C		Paganini-Miozzo syndrome	Uncertain significance (Mar 23, 2020)
X-132628920-G-T		not specified	Uncertain significance (Jan 27, 2022)
X-132628935-T-C		not specified	Uncertain significance (Feb 15, 2023)
X-132628941-C-T		not specified	Uncertain significance (Nov 10, 2022)
X-132628979-C-G		Paganini-Miozzo syndrome	Uncertain significance (Oct 27, 2020)
X-132669116-C-T		not specified	Uncertain significance (Dec 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HS6ST2	protein_coding	protein_coding	ENST00000521489	5	335380

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00101	0.952	124342	2	5	124349	0.0000281

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.40	187	249	0.751	0.0000186	4183
Missense in Polyphen		55	110.85	0.49616		1854
Synonymous	0.752	98	108	0.908	0.00000811	1304
Loss of Function	1.75	7	14.1	0.496	9.67e-7	243

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000156	0.000140
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000786	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.0000140	0.00000889
Middle Eastern	0.0000786	0.0000556
South Asian	0.000105	0.0000654
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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.
• 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: 0.103

Intolerance Scores

• loftool: 0.526
• rvis_EVS: 0.24
• rvis_percentile_EVS: 69.21

Haploinsufficiency Scores

• pHI: 0.445
• hipred: N
• hipred_score: 0.358
• ghis: 0.413

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.111

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hs6st2
• Phenotype: cellular phenotype; normal phenotype

Zebrafish Information Network

• Gene name: hs6st2
• Affected structure: hyaloid vessel
• Phenotype tag: abnormal
• Phenotype quality: irregular spatial pattern

Gene ontology

• Biological process: glycosaminoglycan biosynthetic process;heparan sulfate proteoglycan biosynthetic process, enzymatic modification
• Cellular component: Golgi membrane;nucleoplasm;integral component of membrane
• Molecular function: heparan sulfate 6-O-sulfotransferase activity