GeneBe

CHST3

protein-coding

carbohydrate sulfotransferase 3, the group of Sulfotransferases, membrane bound

Gene summary

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]

MANE transcript

NM_004273.5

Inheritance

AR

ClinVar variants

P:60U:160B:154

Top phenotype

Spondyloepiphyseal dysplasia with congenital joint dislocations

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr10:71,964,395-72,013,558

External References & Databases

Ensembl (ENSG00000122863)NCBI Gene (9469)OMIM (603799)HGNC:1971GenCCUniProt (Q7LGC8)AlphaFoldClinVar (CHST3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~49.2 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spondyloepiphyseal dysplasia with congenital joint dislocationsSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0007738

Submitter: Orphanet

spondyloepiphyseal dysplasia with congenital joint dislocationsDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0007738

Submitter: ClinGen

*CHST3* was first reported in relation to autosomal recessive chondrodysplasia with congenital joint dislocations (SEDCJD) in 2004 (Thiele et al. 2004, PMID: 15215498). SEDCJD, also known as *CHST3*-related skeletal dysplasia is a rare bone disorder characterized by short stature of prenatal onset; dislocation of the knees, hips or elbows; club feet; limitation of range of motion of large joints; progressive kyphosis; and occasional scoliosis. Intellect, vision and hearing are normal. A total of thirteen unique variants (missense, nonsense, frameshift, indel) that have been reported in eleven probands in five publications (PMIDs: 15215498, 18513679, 29453417, 36729370, 37876363) are included in this curation. Variants in this gene segregated in eight additional family members (PMID: 15215498, 37876363). More genetic evidence is available in the literature, however, the maximum score (12pts) has been reached. The mechanism of pathogenicity is predicted to be loss-of-function. This gene-disease relationship is also supported by functional alteration studies in patient cells (PMID: 18513679). In summary, there is definitive evidence supporting the relationship between *CHST3* and autosomal recessive chondrodysplasia with congenital joint dislocations. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Skeletal Disorders GCEP on the meeting date August 4th, 2025 (SOP Version 11).

spondyloepiphyseal dysplasia with congenital joint dislocationsDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0007738

Submitter: G2P

spondyloepiphyseal dysplasia with congenital joint dislocationsSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0007738

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spondyloepiphyseal dysplasia with congenital joint dislocationsAR

Manifestation: Cardiovascular; Musculoskeletal

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: 112567; 9039660; 15368507; 15098240; 15215498; 17618475; 18513679; 18698629; 19320654; 20830804; 22539336Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CHST3 variants in ClinVar

7 Conditions Cataloged
Spondyloepiphyseal dysplasia with congenital joint dislocationsTotal: 332
Inborn genetic diseasesTotal: 50
not providedTotal: 35
not specifiedTotal: 18
CHST3-related disorderTotal: 12
Larsen-like syndrome, B3GAT3 typeTotal: 3
Larsen syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004273.5. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
139
clinvar
2
clinvar
 143
missense
7
clinvar
20
clinvar
154
clinvar
11
clinvar
2
clinvar
 194
nonsense
8
clinvar
3
clinvar
 11
start loss
1
clinvar
 1
frameshift
13
clinvar
7
clinvar
3
clinvar
 23
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
 2
Total29311601504374

Highest pathogenic variant AF is 0.00005929273

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_004273.5RefSeqNP_004264.22MANE Select
ENST00000373115.5EnsemblENSP00000362207.42MANE Select
NM_001441201.1RefSeqNP_001428130.12Standard
NM_001441202.1RefSeqNP_001428131.12Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate - Homo sapiens (human)
  • Metapathway biotransformation Phase I and II
  • Metabolism of carbohydrates
  • Chondroitin sulfate biosynthesis
  • Chondroitin sulfate/dermatan sulfate metabolism

Biological Process

  • carbohydrate metabolic process
  • N-acetylglucosamine metabolic process
  • sulfur compound metabolic process
  • chondroitin sulfate biosynthetic process

Molecular Function

  • N-acetylglucosamine 6-O-sulfotransferase activity
  • sulfotransferase activity
  • chondroitin 6-sulfotransferase activity

Cellular Component

  • Golgi membrane
  • trans-Golgi network
  • integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000373115
Coding exons
2
Length
49200
Individuals with no LoFs
125657
Homozygous LoFs
0
Heterozygous LoFs
21
Defined
125678
p
0.0000835
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.7862873270.8780.00002583044
Missense (PolyPhen)110149.970.733471407
Synonymous0.2191461490.9770.0000128966
Loss of Function2.13614.90.4036.50e-7162

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000630.000062rare
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish0.000100.000099rare
East Asian0.000110.00011rare
Finnish0.000240.00018rare
European (Non-Finnish)0.0000650.000062rare
South Asian0.000170.00016rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of the N-acetylgalactosamine (GalNAc) residue of chondroitin. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices. Can also sulfate Gal residues of keratan sulfate, another glycosaminoglycan, and the Gal residues in sialyl N- acetyllactosamine (sialyl LacNAc) oligosaccharides. May play a role in the maintenance of naive T-lymphocytes in the spleen. {ECO:0000269|PubMed:9714738, ECO:0000269|PubMed:9883891}.;

Recessive Scores

pRec
0.139

Intolerance Scores

LoFtool
0.133
RVIS EVS
-0.34
RVIS percentile EVS
30.37

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.319

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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