HS2ST1

Chr 1AR

heparan sulfate 2-O-sulfotransferase 1

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

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.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Neurofacioskeletal syndrome with or without renal agenesisMIM #619194
AR
0
Active trials
7
Pubs (1 yr)
18
P/LP submissions
17%
P/LP missense
0.47
LOEUF
LOF
Mechanism· G2P
Clinical SummaryHS2ST1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.54) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 44 VUS of 85 total submissions
📖
GeneReview available — HS2ST1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.47LOEUF
pLI 0.545
Z-score 3.27
OE 0.20 (0.100.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.51Z-score
OE missense 0.69 (0.600.80)
135 obs / 194.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.20 (0.100.47)
00.351.4
Missense OE0.69 (0.600.80)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 4 / 19.7Missense obs/exp: 135 / 194.4Syn Z: 0.95

ClinVar Variant Classifications

85 submitted variants in ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic2
VUS44
Likely Benign8
Benign2
16
Pathogenic
2
Likely Pathogenic
44
VUS
8
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
3
12
0
16
Likely Pathogenic
0
0
2
0
2
VUS
0
41
3
0
44
Likely Benign
0
3
0
5
8
Benign
0
0
2
0
2
Total14719572

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HS2ST1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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