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 (220 variants)
• not_provided (66 variants)
• Inborn_genetic_diseases (53 variants)
• B3GAT3-related_disorder (6 variants)
• not_specified (4 variants)
• MULTIPLE_JOINT_DISLOCATIONS,_SHORT_STATURE,_AND_CRANIOFACIAL_DYSMORPHISM_WITHOUT_CONGENITAL_HEART_DEFECTS (3 variants)
• MULTIPLE_JOINT_DISLOCATIONS,_SHORT_STATURE,_AND_CRANIOFACIAL_DYSMORPHISM_WITH_CONGENITAL_HEART_DEFECTS (2 variants)
• Multiple_joint_dislocations,_short_stature,_craniofacial_dysmorphism,_with_or_without_congenital_heart_defects (1 variants)
• See_cases (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. These statistics are base on transcript: NM_000012200.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	64		66
missense	6	4	118	5	1	134
nonsense	3	7	1			11
start loss		4				4
frameshift	6	1	1			8
splice donor/acceptor (+/-2bp)		2				2
Total	15	18	122	69	1

Highest pathogenic variant AF is 0.0000756514

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