CHST3

carbohydrate sulfotransferase 3, the group of Sulfotransferases, membrane bound

Basic information

Region (hg38): 10:71964394-72013558

Links

ENSG00000122863 ∙ NCBI:9469 ∙ OMIM:603799 ∙ HGNC:1971 ∙ Uniprot:Q7LGC8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondyloepiphyseal dysplasia with congenital joint dislocations (Definitive), mode of inheritance: AR
• spondyloepiphyseal dysplasia with congenital joint dislocations (Strong), mode of inheritance: AR
• spondyloepiphyseal dysplasia with congenital joint dislocations (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondyloepiphyseal dysplasia with congenital joint dislocations	AR	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	Cardiovascular; Musculoskeletal	112567; 9039660; 15368507; 15098240; 15215498; 17618475; 18513679; 18698629; 19320654; 20830804; 22539336

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHST3 gene.

• Spondyloepiphyseal dysplasia with congenital joint dislocations (407 variants)
• Larsen syndrome (144 variants)
• Spondyloepiphyseal dysplasia congenita (143 variants)
• Skeletal dysplasia (143 variants)
• not provided (28 variants)
• Inborn genetic diseases (11 variants)
• not specified (9 variants)
• Larsen-like syndrome, B3GAT3 type;Spondyloepiphyseal dysplasia with congenital joint dislocations (1 variants)
• Spondyloepiphyseal dysplasia with congenital joint dislocations;Larsen-like syndrome, B3GAT3 type (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHST3 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			2	62	1	65
missense	2	8	117	4	2	133
nonsense	5	1				6
start loss			1			1
frameshift	8	3	1			12
inframe indel	1		1			2
splice donor/acceptor (+/-2bp)	1	1				2
splice region			1			1
non coding			124	32	26	182
Total	17	13	246	98	29

Highest pathogenic variant AF is 0.0000328

Variants in CHST3

This is a list of pathogenic ClinVar variants found in the CHST3 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-71964502-C-G		Spondyloepiphyseal dysplasia with congenital joint dislocations	Uncertain significance (Jan 13, 2018)
10-71964508-C-G		Spondyloepiphyseal dysplasia with congenital joint dislocations • Spondyloepiphyseal dysplasia congenita • Larsen syndrome • Skeletal dysplasia	Benign (Jun 14, 2016)
10-71964528-G-T		Skeletal dysplasia • Larsen syndrome • Spondyloepiphyseal dysplasia with congenital joint dislocations • Spondyloepiphyseal dysplasia congenita	Likely benign (Jun 14, 2016)
10-71964529-GC-G		Spondyloepiphyseal dysplasia with congenital joint dislocations • Spondyloepiphyseal dysplasia congenita • Skeletal dysplasia • Larsen syndrome	Likely benign (Jun 14, 2016)
10-71964537-C-G		Larsen syndrome • Skeletal dysplasia • Spondyloepiphyseal dysplasia congenita • Spondyloepiphyseal dysplasia with congenital joint dislocations	Uncertain significance (Jun 14, 2016)
10-71964638-C-T		Spondyloepiphyseal dysplasia with congenital joint dislocations	Uncertain significance (Jan 13, 2018)
10-71964671-G-A		Skeletal dysplasia • Larsen syndrome • Spondyloepiphyseal dysplasia with congenital joint dislocations • Spondyloepiphyseal dysplasia congenita	Uncertain significance (Jun 14, 2016)
10-71964700-T-G		Spondyloepiphyseal dysplasia congenita • Larsen syndrome • Spondyloepiphyseal dysplasia with congenital joint dislocations • Skeletal dysplasia	Uncertain significance (Jun 14, 2016)
10-72005455-T-C			Benign (Sep 05, 2018)
10-72005745-G-A		Spondyloepiphyseal dysplasia with congenital joint dislocations	Uncertain significance (Jan 12, 2018)
10-72005792-G-A		Spondyloepiphyseal dysplasia with congenital joint dislocations • Skeletal dysplasia • Spondyloepiphyseal dysplasia congenita • Larsen syndrome	Uncertain significance (Jun 14, 2016)
10-72005844-T-C		Spondyloepiphyseal dysplasia with congenital joint dislocations	Uncertain significance (May 07, 2022)
10-72005849-A-C		Spondyloepiphyseal dysplasia congenita • Spondyloepiphyseal dysplasia with congenital joint dislocations • Larsen syndrome • Inborn genetic diseases • Skeletal dysplasia	Uncertain significance (May 18, 2023)
10-72005849-A-G		Spondyloepiphyseal dysplasia with congenital joint dislocations	Uncertain significance (Oct 08, 2022)
10-72005853-G-A		Spondyloepiphyseal dysplasia with congenital joint dislocations	Uncertain significance (Aug 31, 2021)
10-72005861-T-A		Spondyloepiphyseal dysplasia with congenital joint dislocations	Uncertain significance (Sep 03, 2021)
10-72005864-C-T		Inborn genetic diseases	Uncertain significance (Jul 06, 2021)
10-72005876-C-T		Spondyloepiphyseal dysplasia with congenital joint dislocations	Uncertain significance (Aug 29, 2022)
10-72005878-G-A		Spondyloepiphyseal dysplasia with congenital joint dislocations	Likely benign (Jan 04, 2022)
10-72005879-G-A		Spondyloepiphyseal dysplasia with congenital joint dislocations	Uncertain significance (May 09, 2022)
10-72005890-C-T		Spondyloepiphyseal dysplasia with congenital joint dislocations	Likely benign (Jul 05, 2022)
10-72005896-G-T		Spondyloepiphyseal dysplasia with congenital joint dislocations	Likely benign (Dec 02, 2021)
10-72005899-G-GATGAGAAGCAAATACGCCCT		Spondyloepiphyseal dysplasia with congenital joint dislocations	Pathogenic (May 19, 2022)
10-72005914-C-T		Spondyloepiphyseal dysplasia with congenital joint dislocations	Likely benign (Mar 04, 2022)
10-72005925-T-A		Spondyloepiphyseal dysplasia with congenital joint dislocations	Pathogenic (Jan 15, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHST3	protein_coding	protein_coding	ENST00000373115	2	49200

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00724	0.978	125657	0	21	125678	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.786	287	327	0.878	0.0000258	3044
Missense in Polyphen		110	149.97	0.73347		1407
Synonymous	0.219	146	149	0.977	0.0000128	966
Loss of Function	2.13	6	14.9	0.403	6.50e-7	162

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000922	0.0000910
Ashkenazi Jewish	0.000105	0.0000993
East Asian	0.000112	0.000109
Finnish	0.000238	0.000185
European (Non-Finnish)	0.0000653	0.0000616
Middle Eastern	0.000112	0.000109
South Asian	0.000166	0.000163
Other	0.00	0.00

dbNSFP

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}.
• Pathway: 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;Glycosaminoglycan metabolism;chondroitin sulfate biosynthesis (late stages);Proteoglycan biosynthesis;chondroitin sulfate biosynthesis;Metabolism (Consensus)

Recessive Scores

• pRec: 0.139

Intolerance Scores

• loftool: 0.133
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.37

Haploinsufficiency Scores

• pHI: 0.240
• hipred: Y
• hipred_score: 0.546
• ghis: 0.524

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.319

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chst3
• Phenotype: endocrine/exocrine gland phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: carbohydrate metabolic process;N-acetylglucosamine metabolic process;sulfur compound metabolic process;chondroitin sulfate biosynthetic process
• Cellular component: Golgi membrane;trans-Golgi network;integral component of membrane
• Molecular function: N-acetylglucosamine 6-O-sulfotransferase activity;sulfotransferase activity;chondroitin 6-sulfotransferase activity