CHSY1

chondroitin sulfate synthase 1, the group of Beta 4-glycosyltransferases|Beta 3-glycosyltransferases

Basic information

Region (hg38): 15:101175726-101252048

Links

ENSG00000131873 ∙ NCBI:22856 ∙ OMIM:608183 ∙ HGNC:17198 ∙ Uniprot:Q86X52 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• temtamy preaxial brachydactyly syndrome (Definitive), mode of inheritance: AR
• temtamy preaxial brachydactyly syndrome (Strong), mode of inheritance: AR
• temtamy preaxial brachydactyly syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Temtamy preaxial brachydactyly syndrome	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic	9823490; 21129728; 19952732; 21129727

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHSY1 gene.

• Temtamy preaxial brachydactyly syndrome (134 variants)
• not provided (71 variants)
• Inborn genetic diseases (35 variants)
• not specified (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHSY1 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	42	15	59
missense			93	4	4	101
nonsense	1					1
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding			1	9	15	25
Total	1	0	97	55	34

Variants in CHSY1

This is a list of pathogenic ClinVar variants found in the CHSY1 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-101177394-T-C		Temtamy preaxial brachydactyly syndrome	Likely benign (Sep 13, 2022)
15-101177402-C-A		Temtamy preaxial brachydactyly syndrome	Uncertain significance (Apr 01, 2022)
15-101177420-T-C		Temtamy preaxial brachydactyly syndrome	Uncertain significance (Oct 13, 2023)
15-101177445-T-C		Temtamy preaxial brachydactyly syndrome	Likely benign (Oct 25, 2022)
15-101177462-C-T		Temtamy preaxial brachydactyly syndrome	Uncertain significance (Jan 14, 2022)
15-101177475-G-T		Temtamy preaxial brachydactyly syndrome	Benign (Jan 31, 2024)
15-101177477-T-A		Inborn genetic diseases	Uncertain significance (Apr 05, 2023)
15-101177477-T-C		Temtamy preaxial brachydactyly syndrome	Uncertain significance (Jun 03, 2022)
15-101177490-C-T		Temtamy preaxial brachydactyly syndrome	Likely benign (Nov 20, 2022)
15-101177503-C-G		Temtamy preaxial brachydactyly syndrome	Uncertain significance (Mar 29, 2023)
15-101177504-C-T		Temtamy preaxial brachydactyly syndrome	Uncertain significance (Jul 07, 2020)
15-101177524-T-C		Temtamy preaxial brachydactyly syndrome	Uncertain significance (Jul 12, 2022)
15-101177555-G-A		Inborn genetic diseases	Uncertain significance (Dec 05, 2022)
15-101177565-G-A		Temtamy preaxial brachydactyly syndrome	Benign (Jul 05, 2022)
15-101177578-A-G		Temtamy preaxial brachydactyly syndrome	Uncertain significance (Nov 23, 2022)
15-101177595-C-T		Temtamy preaxial brachydactyly syndrome	Benign (Apr 18, 2022)
15-101177638-T-A			Uncertain significance (Jul 01, 2019)
15-101177677-C-A		Temtamy preaxial brachydactyly syndrome	Uncertain significance (Jun 19, 2023)
15-101177678-C-T		Temtamy preaxial brachydactyly syndrome	Uncertain significance (Jun 18, 2021)
15-101177683-C-T		Temtamy preaxial brachydactyly syndrome	Benign (Jan 31, 2024)
15-101177709-C-T		not specified • Temtamy preaxial brachydactyly syndrome	Benign/Likely benign (Jan 16, 2024)
15-101177757-G-C		Temtamy preaxial brachydactyly syndrome	Likely benign (Aug 26, 2022)
15-101177768-T-C		Temtamy preaxial brachydactyly syndrome	Uncertain significance (Feb 24, 2022)
15-101177775-G-T		Temtamy preaxial brachydactyly syndrome	Likely benign (Oct 17, 2023)
15-101177783-T-C		Inborn genetic diseases	Uncertain significance (Dec 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHSY1	protein_coding	protein_coding	ENST00000254190	3	76210

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.708	0.292	125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.831	376	424	0.886	0.0000250	5269
Missense in Polyphen		110	168.19	0.65404		2040
Synonymous	-1.96	200	168	1.19	0.0000105	1551
Loss of Function	3.81	5	26.0	0.193	0.00000153	310

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000501	0.000492
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000546	0.0000544
Finnish	0.0000930	0.0000924
European (Non-Finnish)	0.0000970	0.0000967
Middle Eastern	0.0000546	0.0000544
South Asian	0.0000654	0.0000653
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has both beta-1,3-glucuronic acid and beta-1,4-N- acetylgalactosamine transferase activity. Transfers glucuronic acid (GlcUA) from UDP-GlcUA and N-acetylgalactosamine (GalNAc) from UDP-GalNAc to the non-reducing end of the elongating chondroitin polymer. Involved in the negative control of osteogenesis likely through the modulation of NOTCH signaling. {ECO:0000269|PubMed:11514575, ECO:0000269|PubMed:21129727}.
• Pathway: Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate - Homo sapiens (human);Metabolism of carbohydrates;Chondroitin sulfate biosynthesis;Chondroitin sulfate/dermatan sulfate metabolism;Glycosaminoglycan metabolism;chondroitin sulfate biosynthesis (late stages);Proteoglycan biosynthesis;chondroitin sulfate biosynthesis;dermatan sulfate biosynthesis;Metabolism;chondroitin and dermatan biosynthesis (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.117
• rvis_EVS: -0.77
• rvis_percentile_EVS: 13.15

Haploinsufficiency Scores

• pHI: 0.377
• hipred: Y
• hipred_score: 0.580
• ghis: 0.528

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.188

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chsy1
• Phenotype: limbs/digits/tail phenotype; vision/eye phenotype; immune system phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: chsy1
• Affected structure: optic furrow
• Phenotype tag: abnormal
• Phenotype quality: open

Gene ontology

• Biological process: chondrocyte development;proximal/distal pattern formation;chondroitin sulfate biosynthetic process;negative regulation of ossification;response to nutrient levels;positive regulation of smoothened signaling pathway;sulfation;bone morphogenesis
• Cellular component: Golgi membrane;extracellular region;membrane;integral component of membrane;Golgi cisterna membrane
• Molecular function: metal ion binding;glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase activity;N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase activity