CHST3

Chr 10AR

carbohydrate sulfotransferase 3

Also known as: C6ST, C6ST1, HSD

NCBI Gene: 9469ENSG00000122863UniProt: Q7LGC8

This gene encodes an enzyme which catalyzes the sulfation of chondroitin, a proteoglycan found in the extracellular matrix and most cells which is involved in cell migration and differentiation. Mutations in this gene are associated with spondylepiphyseal dysplasia and humerospinal dysostosis. [provided by RefSeq, Mar 2009]

Primary Disease Associations & Inheritance

Spondyloepiphyseal dysplasia with congenital joint dislocationsMIM #143095
AR
487
ClinVar variants
70
Pathogenic / LP
0.01
pLI score
1
Active trials
Clinical Summary— CHST3
🧬
Gene-Disease Validity (ClinGen)
spondyloepiphyseal dysplasia with congenital joint dislocations · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
70 Pathogenic / Likely Pathogenic· 220 VUS of 487 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.80LOEUF
pLI 0.007
Z-score 2.13
OE 0.40 (0.22–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.79Z-score
OE missense 0.88 (0.80–0.97)
287 obs / 327.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.40 (0.22–0.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.80–0.97)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 6 / 14.9Missense obs/exp: 287 / 327.0Syn Z: 0.22

ClinVar Variant Classifications

487 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45
Likely Pathogenic25
VUS220
Likely Benign150
Benign35
Conflicting12
45
Pathogenic
25
Likely Pathogenic
220
VUS
150
Likely Benign
35
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
9
25
0
45
Likely Pathogenic
7
15
3
0
25
VUS
3
148
67
2
220
Likely Benign
0
7
12
131
150
Benign
0
3
27
5
35
Conflicting
—12
Total21182134138487

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

View in ClinVar →

Protein Context — Lollipop Plot

CHST3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CHST3-related spondyloepiphyseal dysplasia with congenital joint dislocations

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spondyloepiphyseal dysplasia with congenital joint dislocations

MIM #143095

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — CHST3
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A Chinese case of CHST3-related skeletal dysplasia and a systematic review.
Liang H et al.·Endocrine
2023Case report
CHST3, PGBD5, and SLIT2 can be identified as potential genes for the diagnosis and treatment of osteoporosis and sarcopenia.
Yang X et al.·Sci Rep
2025
Recurrent c.776T>C mutation in CHST3 with four other novel mutations and a literature review.
Duz MB et al.·Clin Dysmorphol
2020Review
Indian patients with CHST3-related chondrodysplasia with congenital joint dislocations.
Singh S et al.·Am J Med Genet A
2024Cohort
A novel CHST3 allele associated with spondyloepiphyseal dysplasia and hearing loss in Pakistani kindred.
Waryah AM et al.·Clin Genet
2016
CHST3-related skeletal dysplasia in 14 patients: Identification of 8 novel variants and further expansion of the phenotypic spectrum.
Otaify GA et al.·Am J Med Genet A
2023Cohort
Carbohydrate sulfotransferases: a review of emerging diagnostic and prognostic applications.
Begolli G et al.·Biochem Med (Zagreb)
2023Review
Biallelic variants in CHST3 cause Spondyloepiphyseal dysplasia with joint dislocations in three Pakistani kindreds.
Kausar M et al.·BMC Musculoskelet Disord
2022Case report
CHST3 and CHST13 polymorphisms as predictors of bosentan-induced liver toxicity in Japanese patients with pulmonary arterial hypertension.
Yorifuji K et al.·Pharmacol Res
2018Cohort
Chondroitin sulfate mediates liver responses to injury induced by dual endothelin receptor inhibition.
Ryanto GRT et al.·Can J Physiol Pharmacol
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
PreDiabetes

Pharmacogenetics of the Response to GLP-1 in Mexican-Americans With Prediabetes

RECRUITING
NCT05119179Phase PHASE4The University of Texas Health Science Center, HoustonStarted 2021-11-22
Semaglutide

External Resources

Links to major genomics databases and tools