B3GAT3

beta-1,3-glucuronyltransferase 3, the group of Beta-1,3-glucuronyltransferases

Basic information

Region (hg38): 11:62615296-62622154

Links

ENSG00000149541 ∙ NCBI:26229 ∙ OMIM:606374 ∙ HGNC:923 ∙ Uniprot:O94766 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Larsen-like syndrome, B3GAT3 type (Limited), mode of inheritance: AR
• Larsen-like syndrome, B3GAT3 type (Strong), mode of inheritance: AR
• Larsen-like syndrome, B3GAT3 type (Moderate), mode of inheritance: AR
• Larsen-like syndrome, B3GAT3 type (Strong), mode of inheritance: AR
• Larsen-like syndrome, B3GAT3 type (Supportive), mode of inheritance: AR
• complex neurodevelopmental disorder (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects	AR	General	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Musculoskeletal	21763480; 24668659

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the B3GAT3 gene.

• Larsen-like syndrome, B3GAT3 type (9 variants)
• MULTIPLE JOINT DISLOCATIONS, SHORT STATURE, AND CRANIOFACIAL DYSMORPHISM WITHOUT CONGENITAL HEART DEFECTS (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the B3GAT3 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	55		57
missense	3	2	93	1	1	100
nonsense	4	5	1			10
start loss		3				3
frameshift	3	1	1			5
inframe indel			4			4
splice donor/acceptor (+/-2bp)		2				2
splice region			5	5		10
non coding				26	8	34
Total	10	13	101	82	9

Highest pathogenic variant AF is 0.0000131

Variants in B3GAT3

This is a list of pathogenic ClinVar variants found in the B3GAT3 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-62615690-TG-T			Likely benign (Jul 20, 2022)
11-62615696-C-T			Likely benign (Nov 13, 2020)
11-62615703-A-C		Larsen-like syndrome, B3GAT3 type	Uncertain significance (Feb 03, 2022)
11-62615709-C-T		Larsen-like syndrome, B3GAT3 type	Uncertain significance (Oct 13, 2021)
11-62615711-A-G		Larsen-like syndrome, B3GAT3 type • Inborn genetic diseases	Uncertain significance (Sep 29, 2023)
11-62615716-TG-T		Larsen-like syndrome, B3GAT3 type	Uncertain significance (Jun 16, 2019)
11-62615723-G-C		Larsen-like syndrome, B3GAT3 type	Likely pathogenic (Aug 29, 2023)
11-62615724-A-G		Larsen-like syndrome, B3GAT3 type	Uncertain significance (Aug 01, 2023)
11-62615728-C-T		Larsen-like syndrome, B3GAT3 type	Likely benign (Jul 22, 2023)
11-62615729-C-T		Larsen-like syndrome, B3GAT3 type	Uncertain significance (Apr 14, 2023)
11-62615730-G-A		Larsen-like syndrome, B3GAT3 type	Conflicting classifications of pathogenicity (Nov 26, 2024)
11-62615730-G-T		Larsen-like syndrome, B3GAT3 type	Likely benign (Nov 01, 2021)
11-62615738-C-T		Larsen-like syndrome, B3GAT3 type • Inborn genetic diseases	Uncertain significance (Dec 29, 2023)
11-62615739-G-A		Larsen-like syndrome, B3GAT3 type	Uncertain significance (Nov 17, 2023)
11-62615741-T-A		Larsen-like syndrome, B3GAT3 type	Uncertain significance (Jul 31, 2021)
11-62615744-A-G		Inborn genetic diseases	Uncertain significance (Nov 25, 2024)
11-62615754-C-G		Larsen-like syndrome, B3GAT3 type	Uncertain significance (Oct 11, 2023)
11-62615757-G-A		Larsen-like syndrome, B3GAT3 type	Uncertain significance (Mar 19, 2022)
11-62615762-A-C		Larsen-like syndrome, B3GAT3 type	Uncertain significance (Aug 16, 2022)
11-62615779-C-T		Larsen-like syndrome, B3GAT3 type	Likely benign (Jan 29, 2024)
11-62615780-C-G			Uncertain significance (Feb 16, 2023)
11-62615780-C-T		See cases	Uncertain significance (Nov 22, 2022)
11-62615802-G-A		Larsen-like syndrome, B3GAT3 type	Uncertain significance (Jun 16, 2022)
11-62615805-C-T		Larsen-like syndrome, B3GAT3 type	Likely benign (Jan 25, 2024)
11-62615806-C-T		Larsen-like syndrome, B3GAT3 type	Uncertain significance (Jul 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
B3GAT3	protein_coding	protein_coding	ENST00000265471	5	6880

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.71e-8	0.299	125715	0	30	125745	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.692	178	206	0.864	0.0000136	2087
Missense in Polyphen		47	54.975	0.85493		604
Synonymous	-0.226	93	90.3	1.03	0.00000514	768
Loss of Function	0.592	13	15.5	0.838	9.39e-7	139

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000117	0.000117
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.00	0.00
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000152	0.000149
Middle Eastern	0.00	0.00
South Asian	0.000164	0.000163
Other	0.000331	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Glycosaminoglycans biosynthesis (PubMed:25893793). Involved in forming the linkage tetrasaccharide present in heparan sulfate and chondroitin sulfate. Transfers a glucuronic acid moiety from the uridine diphosphate-glucuronic acid (UDP-GlcUA) to the common linkage region trisaccharide Gal-beta-1,3-Gal-beta-1,4- Xyl covalently bound to a Ser residue at the glycosaminylglycan attachment site of proteoglycans. Can also play a role in the biosynthesis of l2/HNK-1 carbohydrate epitope on glycoproteins. Shows strict specificity for Gal-beta-1,3-Gal-beta-1,4-Xyl, exhibiting negligible incorporation into other galactoside substrates including Galbeta1-3Gal beta1-O-benzyl, Galbeta1- 4GlcNAc and Galbeta1-4Glc. Stimulates 2-phosphoxylose phosphatase activity of PXYLP1 in presence of uridine diphosphate-glucuronic acid (UDP-GlcUA) during completion of linkage region formation (PubMed:24425863). {ECO:0000269|PubMed:24425863, ECO:0000269|PubMed:25893793}.
• Disease: DISEASE: Multiple joint dislocations, short stature, and craniofacial dysmorphism with or without congenital heart defects (JDSCD) [MIM:245600]: An autosomal recessive disease characterized by dysmorphic facies, bilateral dislocations of the elbows, hips, and knees, clubfeet, and short stature, as well as cardiovascular defects. {ECO:0000269|PubMed:21763480, ECO:0000269|PubMed:24668659, ECO:0000269|PubMed:25893793, ECO:0000269|PubMed:26086840}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate - Homo sapiens (human);Glycosaminoglycan biosynthesis - heparan sulfate / heparin - Homo sapiens (human);Metabolism of carbohydrates;A tetrasaccharide linker sequence is required for GAG synthesis;Heparan sulfate/heparin (HS-GAG) metabolism;Chondroitin sulfate/dermatan sulfate metabolism;Glycosaminoglycan metabolism;Proteoglycan biosynthesis;glycoaminoglycan-protein linkage region biosynthesis;chondroitin sulfate biosynthesis;heparan sulfate biosynthesis;dermatan sulfate biosynthesis;Metabolism (Consensus)

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.600
• rvis_EVS: -0.2
• rvis_percentile_EVS: 38.82

Haploinsufficiency Scores

• pHI: 0.248
• hipred: N
• hipred_score: 0.291
• ghis: 0.567

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.434

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: B3gat3
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: b3gat3
• Affected structure: pharyngeal arch 3-7
• Phenotype tag: abnormal
• Phenotype quality: shape

Gene ontology

• Biological process: glycosaminoglycan biosynthetic process;protein glycosylation;heparan sulfate proteoglycan biosynthetic process;glycosaminoglycan metabolic process;positive regulation of catalytic activity;regulation of phosphoprotein phosphatase activity;chondroitin sulfate proteoglycan biosynthetic process;dermatan sulfate proteoglycan biosynthetic process;positive regulation of intracellular protein transport
• Cellular component: Golgi membrane;Golgi apparatus;cis-Golgi network;membrane;integral component of membrane;extracellular exosome
• Molecular function: protein binding;galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase activity;glucuronosyltransferase activity;metal ion binding;protein phosphatase activator activity