CHSY1

Chr 15

chondroitin sulfate synthase 1

Also known as: CHSY, CSS1, ChSy-1, TPBS

NCBI Gene: 22856ENSG00000131873UniProt: Q86X52

This gene encodes a member of the chondroitin N-acetylgalactosaminyltransferase family. These enzymes possess dual glucuronyltransferase and galactosaminyltransferase activity and play critical roles in the biosynthesis of chondroitin sulfate, a glycosaminoglycan involved in many biological processes including cell proliferation and morphogenesis. Decreased expression of this gene may play a role in colorectal cancer, and mutations in this gene are a cause of temtamy preaxial brachydactyly syndrome. [provided by RefSeq, Dec 2011]

Primary Disease Associations & Inheritance

UniProtTemtamy preaxial brachydactyly syndrome
422
ClinVar variants
86
Pathogenic / LP
0.71
pLI score
0
Active trials
Clinical Summary— CHSY1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.71) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
86 Pathogenic / Likely Pathogenic· 196 VUS of 422 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.41LOEUF
pLI 0.708
Z-score 3.81
OE 0.19 (0.10–0.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
0.83Z-score
OE missense 0.89 (0.81–0.96)
376 obs / 424.1 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.0.19 (0.10–0.41)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.81–0.96)
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.1.19
0≤1.21.6
LoF obs/exp: 5 / 26.0Missense obs/exp: 376 / 424.1Syn Z: -1.96

ClinVar Variant Classifications

422 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic80
Likely Pathogenic6
VUS196
Likely Benign92
Benign39
Conflicting6
80
Pathogenic
6
Likely Pathogenic
196
VUS
92
Likely Benign
39
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
77
0
80
Likely Pathogenic
0
0
6
0
6
VUS
0
179
15
2
196
Likely Benign
0
6
18
68
92
Benign
0
4
21
14
39
Conflicting
—6
Total219013784419

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

View in ClinVar →

Protein Context — Lollipop Plot

CHSY1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CHSY1-related Temtamy preaxial brachydactyly syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CHSY1 promotes CD8(+) T cell exhaustion through activation of succinate metabolism pathway leading to colorectal cancer liver metastasis based on CRISPR/Cas9 screening.
Sun G et al.·J Exp Clin Cancer Res
2023
CHSY1 is upregulated and acts as tumor promotor in gastric cancer through regulating cell proliferation, apoptosis, and migration.
Liu J et al.·Cell Cycle
2021
Genome-wide association study reveals CBX7 as a novel susceptibility gene associated with primary spontaneous pneumothorax in the Chinese Han population.
Xu L et al.·Eur Respir J
2025
15q26.3 deletions distal to IGF1R cause growth retardation, congenital heart defect and skeletal anomalies: Case report and review of literature.
Sivakumaran TA et al.·Am J Med Genet A
2023Review
Clinical, cytogenetic and molecular analyses of a rare case with ring chromosome 15 and review of the literature.
Shao HY et al.·Taiwan J Obstet Gynecol
2020Review
CeRNA network reveals potential diagnostic biomarkers or immunotherapy targets for Hypopharyngeal squamous cell carcinoma.
Yang X et al.·Braz J Otorhinolaryngol
2025
Tumor-dependent Effects of Proteoglycans and Various Glycosaminoglycan Synthesizing Enzymes and Sulfotransferases on Patients' Outcome.
Subbarayan K et al.·Curr Cancer Drug Targets
2019Cohort
Epigenetic profiling of growth plate chondrocytes sheds insight into regulatory genetic variation influencing height.
Guo M et al.·Elife
2017
Effect of Genetic Polymorphism Including NUP153 and SVEP1 on the Pharmacokinetics and Pharmacodynamics of Ticagrelor in Healthy Chinese Subjects.
Xiang Q et al.·Clin Drug Investig
2022
A FURTHER PATIENT OF PURE 15q DELETION: CLINICAL AND MOLECULAR CYTOGENETIC FINDINGS.
Solmaz AE et al.·Genet Couns
2016Case report
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools