B3GALT6

beta-1,3-galactosyltransferase 6, the group of Beta 3-glycosyltransferases

Basic information

Region (hg38): 1:1232236-1235041

Links

ENSG00000176022 ∙ NCBI:126792 ∙ OMIM:615291 ∙ HGNC:17978 ∙ Uniprot:Q96L58 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures (Definitive), mode of inheritance: AR
• Ehlers-Danlos syndrome, spondylodysplastic type, 2 (Strong), mode of inheritance: AR
• Ehlers-Danlos syndrome, spondylodysplastic type, 2 (Strong), mode of inheritance: AR
• spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures (Strong), mode of inheritance: AR
• Ehlers-Danlos syndrome, spondylodysplastic type, 2 (Strong), mode of inheritance: AR
• spondyloepimetaphyseal dysplasia with joint laxity (Supportive), mode of inheritance: AR
• Ehlers-Danlos syndrome, spondylodysplastic type, 2 (Strong), mode of inheritance: AR
• spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ehlers-Danlos syndrome, spondylodysplastic type, 2; Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures; Al-Gazali syndrome	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	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	23664117; 23664118; 25149931; 29443383

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the B3GALT6 gene.

• Ehlers-Danlos syndrome, spondylodysplastic type, 2;Spondyloepimetaphyseal dysplasia with joint laxity (134 variants)
• not provided (86 variants)
• Spondyloepimetaphyseal dysplasia with joint laxity;Ehlers-Danlos syndrome, spondylodysplastic type, 2 (84 variants)
• Inborn genetic diseases (35 variants)
• Ehlers-Danlos syndrome, spondylodysplastic type, 2 (14 variants)
• not specified (12 variants)
• Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures (11 variants)
• Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures;Ehlers-Danlos syndrome, spondylodysplastic type, 2 (3 variants)
• Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with fractures (2 variants)
• Al-Gazali syndrome (2 variants)
• Al-Gazali syndrome;Ehlers-Danlos syndrome, spondylodysplastic type, 2;Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures (2 variants)
• Ehlers-Danlos syndrome, spondylodysplastic type, 2;Al-Gazali syndrome;Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures (1 variants)
• B3GALT6-related condition (1 variants)
• Al-Gazali syndrome;Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures;Ehlers-Danlos syndrome, spondylodysplastic type, 2 (1 variants)
• Spondyloepiphyseal dysplasia (1 variants)
• Ehlers-Danlos syndrome, spondylodysplastic type, 2;Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the B3GALT6 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			4	80		84
missense	5		137	1	2	145
nonsense		3	2			5
start loss	3	1				4
frameshift	1	1	12			14
inframe indel			5		1	6
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	2		3
Total	9	5	161	83	3

Highest pathogenic variant AF is 0.0000555

Variants in B3GALT6

This is a list of pathogenic ClinVar variants found in the B3GALT6 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-1232241-G-A		not specified	Likely benign (Feb 12, 2018)
1-1232256-G-A		not specified	Likely benign (Oct 20, 2016)
1-1232274-G-A			Uncertain significance (Nov 13, 2019)
1-1232279-A-G		Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures • Ehlers-Danlos syndrome, spondylodysplastic type, 2;Spondyloepimetaphyseal dysplasia with joint laxity • B3GALT6-related disorder	Pathogenic (Nov 10, 2023)
1-1232280-T-A		Spondyloepimetaphyseal dysplasia with joint laxity;Ehlers-Danlos syndrome, spondylodysplastic type, 2	Likely pathogenic (Jan 29, 2024)
1-1232280-T-C		Spondyloepimetaphyseal dysplasia with joint laxity;Ehlers-Danlos syndrome, spondylodysplastic type, 2	Pathogenic (Aug 17, 2023)
1-1232281-G-A		Spondyloepimetaphyseal dysplasia with joint laxity;Ehlers-Danlos syndrome, spondylodysplastic type, 2	Pathogenic (Nov 04, 2023)
1-1232285-C-G		Inborn genetic diseases	Uncertain significance (Jul 19, 2023)
1-1232285-C-T		Ehlers-Danlos syndrome, spondylodysplastic type, 2;Spondyloepimetaphyseal dysplasia with joint laxity	Likely benign (Dec 09, 2023)
1-1232288-C-G		Spondyloepimetaphyseal dysplasia with joint laxity;Ehlers-Danlos syndrome, spondylodysplastic type, 2	Uncertain significance (Mar 12, 2022)
1-1232288-C-T		Ehlers-Danlos syndrome, spondylodysplastic type, 2;Spondyloepimetaphyseal dysplasia with joint laxity	Likely benign (Oct 25, 2023)
1-1232290-G-A		Spondyloepimetaphyseal dysplasia with joint laxity;Ehlers-Danlos syndrome, spondylodysplastic type, 2	Likely benign (Nov 04, 2023)
1-1232289-T-TGCGGCGGGCGTGGCG		Spondyloepimetaphyseal dysplasia with joint laxity;Ehlers-Danlos syndrome, spondylodysplastic type, 2	Benign (Jan 29, 2024)
1-1232289-T-TGCGGCGGGCGTG		Ehlers-Danlos syndrome, spondylodysplastic type, 2;Spondyloepimetaphyseal dysplasia with joint laxity	Uncertain significance (Oct 13, 2022)
1-1232289-T-TGCGGCGGGCGTGGCGGCGGCGGGCGTGGCG		Spondyloepimetaphyseal dysplasia with joint laxity;Ehlers-Danlos syndrome, spondylodysplastic type, 2	Uncertain significance (Sep 27, 2022)
1-1232291-C-T		Spondyloepimetaphyseal dysplasia with joint laxity;Ehlers-Danlos syndrome, spondylodysplastic type, 2	Uncertain significance (Mar 23, 2021)
1-1232294-C-A		Spondyloepimetaphyseal dysplasia with joint laxity;Ehlers-Danlos syndrome, spondylodysplastic type, 2	Likely benign (Sep 28, 2023)
1-1232294-C-T		Ehlers-Danlos syndrome, spondylodysplastic type, 2 • Spondyloepimetaphyseal dysplasia with joint laxity;Ehlers-Danlos syndrome, spondylodysplastic type, 2	Uncertain significance (Apr 04, 2022)
1-1232295-G-A		Spondyloepimetaphyseal dysplasia with joint laxity;Ehlers-Danlos syndrome, spondylodysplastic type, 2 • Inborn genetic diseases • Al-Gazali syndrome;Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures;Ehlers-Danlos syndrome, spondylodysplastic type, 2	Uncertain significance (Apr 12, 2023)
1-1232300-T-G			Uncertain significance (Feb 05, 2015)
1-1232300-T-TGGCGGCGGCG		Spondyloepimetaphyseal dysplasia with joint laxity;Ehlers-Danlos syndrome, spondylodysplastic type, 2	Uncertain significance (Nov 15, 2021)
1-1232304-G-T		Spondyloepimetaphyseal dysplasia with joint laxity;Ehlers-Danlos syndrome, spondylodysplastic type, 2	Uncertain significance (Feb 18, 2022)
1-1232303-C-CGGCGGCG		Spondyloepimetaphyseal dysplasia with joint laxity;Ehlers-Danlos syndrome, spondylodysplastic type, 2	Uncertain significance (Feb 08, 2023)
1-1232306-C-T		Inborn genetic diseases	Uncertain significance (Oct 28, 2022)
1-1232309-C-T		Ehlers-Danlos syndrome, spondylodysplastic type, 2;Spondyloepimetaphyseal dysplasia with joint laxity	Uncertain significance (Mar 29, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
B3GALT6	protein_coding	protein_coding	ENST00000379198	1	2793

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0227	0.779	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.26	93	134	0.694	0.0000112	1992
Missense in Polyphen		26	48.604	0.53493		698
Synonymous	0.413	61	65.2	0.935	0.00000586	751
Loss of Function	0.932	3	5.32	0.564	2.32e-7	77

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Beta-1,3-galactosyltransferase that transfers galactose from UDP-galactose to substrates with a terminal beta-linked galactose residue. Has a preference for galactose-beta-1,4-xylose that is found in the linker region of glycosaminoglycans, such as heparan sulfate and chondroitin sulfate. Has no activity towards substrates with terminal glucosamine or galactosamine residues. {ECO:0000269|PubMed:11551958}.
• Disease: DISEASE: Spondyloepimetaphyseal dysplasia with joint laxity, 1, with or without fractures (SEMDJL1) [MIM:271640]: A bone disease characterized by vertebral abnormalities and ligamentous laxity that result in spinal misalignment and progressive severe kyphoscoliosis, thoracic asymmetry, and respiratory compromise resulting in early death. Additional skeletal features include elbow deformities with radial head dislocation, dislocated hips, clubfeet, and tapered fingers with spatulate distal phalanges. Many affected children have an oval face, flat midface, prominent eyes with blue sclerae, and a long philtrum. Palatal abnormalities and congenital heart disease are also observed. {ECO:0000269|PubMed:23664117, ECO:0000269|PubMed:23664118}. 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)

Haploinsufficiency Scores

• pHI: 0.153
• hipred: N
• hipred_score: 0.429
• ghis: 0.526

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.736

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: B3galt6

Gene ontology

• Biological process: glycosaminoglycan biosynthetic process;protein glycosylation;heparan sulfate proteoglycan biosynthetic process;glycosaminoglycan metabolic process;chondroitin sulfate biosynthetic process
• Cellular component: Golgi membrane;endoplasmic reticulum;Golgi apparatus;Golgi medial cisterna;membrane;integral component of membrane;Golgi cisterna membrane
• Molecular function: galactosyltransferase activity;UDP-galactosyltransferase activity;galactosylxylosylprotein 3-beta-galactosyltransferase activity