B3GALT6

Summary

B3GALT6 (beta-1,3-galactosyltransferase 6, HGNC:17978) is a protein-coding gene on chromosome 1p36.33, encoding Beta-1,3-galactosyltransferase 6 (Q96L58). Beta-1,3-galactosyltransferase that transfers galactose from UDP-galactose to substrates with a terminal beta-linked galactose residue.

The enzyme encoded by this intronless gene is a beta-1,3-galactosyltransferase found in the medial Golgi apparatus, where it catalyzes the transfer of galactose from UDP-galactose to substrates containing a terminal beta-linked galactose moiety. The encoded enzyme has a particular affinity for galactose-beta-1,4-xylose found in the linker region of glycosamines. This enzyme is required for glycosaminoglycan synthesis.

Source: NCBI Gene 126792 — RefSeq curated summary.

At a glance

• Gene–disease (curated): B3GALT6-congenital disorder of glycosylation (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 414 total — 24 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 157
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_080605

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17978
Approved symbol	B3GALT6
Name	beta-1,3-galactosyltransferase 6
Location	1p36.33
Locus type	gene with protein product
Status	Approved
Aliases	beta3GalT6
Ensembl gene	ENSG00000176022
Ensembl biotype	protein_coding
OMIM	615291
Entrez	126792

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000379198

RefSeq mRNA: 1 — MANE Select: NM_080605 NM_080605

CCDS: CCDS13

Canonical transcript exons

ENST00000379198 — 1 exons

Exon	Start	End
ENSE00001480062	1232237	1235041

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 91.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.1630 / max 31.8128, expressed in 1757 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
77	7.1630	1757

Top tissues by expression

248 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	91.05	gold quality
endothelial cell	CL:0000115	90.71	gold quality
cartilage tissue	UBERON:0002418	90.30	gold quality
middle temporal gyrus	UBERON:0002771	88.64	gold quality
decidua	UBERON:0002450	88.22	gold quality
epithelial cell of pancreas	CL:0000083	88.15	silver quality
tendon of biceps brachii	UBERON:0008188	87.88	gold quality
parotid gland	UBERON:0001831	87.32	gold quality
cortical plate	UBERON:0005343	86.62	gold quality
visceral pleura	UBERON:0002401	86.47	gold quality
pancreatic ductal cell	CL:0002079	86.45	gold quality
gingival epithelium	UBERON:0001949	86.19	gold quality
stromal cell of endometrium	CL:0002255	85.82	gold quality
tibia	UBERON:0000979	85.48	gold quality
nipple	UBERON:0002030	85.00	gold quality
apex of heart	UBERON:0002098	84.99	gold quality
parietal pleura	UBERON:0002400	84.84	gold quality
kidney epithelium	UBERON:0004819	84.63	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.36	gold quality
amniotic fluid	UBERON:0000173	83.74	gold quality
gingiva	UBERON:0001828	83.67	gold quality
primary visual cortex	UBERON:0002436	83.03	gold quality
granulocyte	CL:0000094	82.33	gold quality
upper arm skin	UBERON:0004263	82.33	silver quality
ileal mucosa	UBERON:0000331	81.97	silver quality
occipital lobe	UBERON:0002021	81.68	gold quality
germinal epithelium of ovary	UBERON:0001304	81.10	gold quality
lower lobe of lung	UBERON:0008949	81.08	gold quality
superior frontal gyrus	UBERON:0002661	81.01	gold quality
tibialis anterior	UBERON:0001385	80.95	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting B3GALT6, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-605-5P	98.79	68.24	1161
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-561-5P	98.25	68.13	1365
HSA-MIR-96-3P	97.47	68.03	839
HSA-MIR-148B-5P	97.29	66.30	992
HSA-MIR-6874-3P	97.29	66.34	975

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 9)

• B3GALT6 encoding an enzyme involved in the biosynthesis of the GAG linker region is responsible for a severe skeletal dysplasia, spondyloepimetaphyseal dysplasia with joint laxity type 1. (PMID:23664117)
• Genetic association between B3GALT6 and Ehlers-Danlos-syndrome-like connective tissue disorder in 3 families. (PMID:23664118)
• These findings confirm the involvement of B3GALT6 in the pathogenesis of Al-Gazali syndrome. (PMID:29443383)
• This study redefines the phenotype associated with B3GALT6 mutations on the basis of clinical, molecular and biochemical data in 12 patients, and provides an in-depth assessment of beta3GalT6 activity and glycosaminoglycan synthesis. (PMID:29931299)
• Defineed some of the clinical features of B4GALT7 and B3GALT6-related conditions and underlined the extreme hypermobility of distal joints and the soft, doughy skin on the hands and feet as features that may be useful as the first clues for a correct diagnosis. (PMID:31614862)
• Altered Expression of Aggrecan, FAM20B, B3GALT6, and EXTL2 in Patients with Osteoarthritis and Kashin-Beck Disease. (PMID:32517548)
• Keratoconus in a patient with B3GALT6-related disorder. (PMID:33631843)
• Broadening the phenotypic spectrum of Beta3GalT6-associated phenotypes. (PMID:34159694)
• B3GALT6 promotes dormant breast cancer cell survival and recurrence by enabling heparan sulfate-mediated FGF signaling. (PMID:38065100)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	b3galt6	ENSDARG00000038414
mus_musculus	B3galt6	ENSMUSG00000050796
rattus_norvegicus	B3galt6	ENSRNOG00000019979
drosophila_melanogaster	beta3GalTII	FBGN0033315
caenorhabditis_elegans		WBGENE00005020

Paralogs (15): B3GNT7 (ENSG00000156966), B3GALT2 (ENSG00000162630), B3GALNT2 (ENSG00000162885), B3GALNT1 (ENSG00000169255), B3GNT2 (ENSG00000170340), B3GALT1 (ENSG00000172318), B3GNT4 (ENSG00000176383), B3GNT5 (ENSG00000176597), B3GNT8 (ENSG00000177191), B3GNT3 (ENSG00000179913), B3GALT5 (ENSG00000183778), B3GNT6 (ENSG00000198488), B3GALT9 (ENSG00000214654), B3GALT4 (ENSG00000235863), B3GNT9 (ENSG00000237172)

Protein

Protein identifiers

Beta-1,3-galactosyltransferase 6 — Q96L58 (reviewed: Q96L58)

Alternative names: GAG GalTII, Galactosyltransferase II, Galactosylxylosylprotein 3-beta-galactosyltransferase, UDP-Gal:betaGal beta 1,3-galactosyltransferase polypeptide 6

All UniProt accessions (1): Q96L58

UniProt curated annotations — full annotation on UniProt →

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.

Subcellular location. Golgi apparatus. Golgi stack membrane.

Tissue specificity. Ubiquitous.

Disease relevance. Ehlers-Danlos syndrome, spondylodysplastic type, 2 (EDSSPD2) [MIM:615349] A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSSPD2 is an autosomal recessive form characterized by an aged appearance, developmental delay, short stature, craniofacial disproportion, generalized osteopenia, defective wound healing, hypermobile joints, hypotonic muscles, and loose but elastic skin. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. Al-Gazali syndrome (ALGAZ) [MIM:609465] A severe disorder characterized by prenatal growth retardation, large joints contractures, camptodactyly, bilateral talipes equinovarus, small mouth, anterior segment anomalies of the eyes, and early lethality. The transmission pattern of the disorder is consistent with autosomal recessive inheritance. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Glycan metabolism; chondroitin sulfate biosynthesis. Glycan metabolism; heparan sulfate biosynthesis.

Similarity. Belongs to the glycosyltransferase 31 family.

RefSeq proteins (1): NP_542172* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002659	Glyco_trans_31	Family

Pfam: PF01762

Enzyme classification (BRENDA):

• EC 2.4.1.134 — galactosylxylosylprotein 3-beta-galactosyltransferase (BRENDA: 6 organisms, 19 substrates, 0 inhibitors, 2 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PYRIDINE 3-O-BETA-GALACTOSIDE	100	1
UDPGALACTOSE	1.05	1

Catalyzed reactions (Rhea), 1 shown:

• 3-O-(beta-D-galactosyl-(1->4)-beta-D-xylosyl)-L-seryl-[protein] + UDP-alpha-D-galactose = 3-O-(beta-D-galactosyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-xylosyl)-L-seryl-[protein] + UDP + H(+) (RHEA:11780)

UniProt features (24 total): sequence variant 18, topological domain 2, chain 1, transmembrane region 1, sequence conflict 1, glycosylation site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9SP7	X-RAY DIFFRACTION	1.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96L58-F1	91.06	0.80

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 131

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-1971475	Glycosaminoglycan-protein linkage region biosynthesis
R-HSA-4420332	Defective B3GALT6 causes EDSP2 and SEMDJL1
R-HSA-1430728	Metabolism
R-HSA-1630316	Glycosaminoglycan metabolism
R-HSA-1638091	Heparan sulfate/heparin (HS-GAG) metabolism
R-HSA-1643685	Disease
R-HSA-1793185	Chondroitin sulfate/dermatan sulfate metabolism
R-HSA-3560782	Diseases associated with glycosaminoglycan metabolism
R-HSA-3781865	Diseases of glycosylation
R-HSA-5668914	Diseases of metabolism
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives

MSigDB gene sets: 473 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, YY1_Q6, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_AMINOGLYCAN_BIOSYNTHETIC_PROCESS, GOBP_CHONDROITIN_SULFATE_PROTEOGLYCAN_BIOSYNTHETIC_PROCESS, YY1_02, GOBP_HEPARAN_SULFATE_PROTEOGLYCAN_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_AMINOGLYCAN_METABOLIC_PROCESS, CCCNNNNNNAAGWT_UNKNOWN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_CHONDROITIN_SULFATE_PROTEOGLYCAN_METABOLIC_PROCESS, MODULE_568

GO Biological Process (9): glycosaminoglycan biosynthetic process (GO:0006024), protein O-linked glycosylation (GO:0006493), heparan sulfate proteoglycan biosynthetic process (GO:0015012), proteoglycan biosynthetic process (GO:0030166), chondroitin sulfate proteoglycan biosynthetic process (GO:0050650), dermatan sulfate proteoglycan biosynthetic process (GO:0050651), glycosaminoglycan-protein linkage region biosynthetic process (GO:0120532), obsolete protein glycosylation (GO:0006486), glycosaminoglycan metabolic process (GO:0030203)

GO Molecular Function (5): UDP-galactosyltransferase activity (GO:0035250), galactosylxylosylprotein 3-beta-galactosyltransferase activity (GO:0047220), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), hexosyltransferase activity (GO:0016758)

GO Cellular Component (5): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), Golgi medial cisterna (GO:0005797), membrane (GO:0016020), Golgi cisterna membrane (GO:0032580)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Glycosaminoglycan metabolism	3
Diseases associated with glycosaminoglycan metabolism	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Diseases of glycosylation	1
Diseases of metabolism	1
Disease	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein O-linked glycosylation via xylose	4
proteoglycan biosynthetic process	3
glycoprotein biosynthetic process	2
Golgi cisterna	2
aminoglycan biosynthetic process	1
glycosaminoglycan metabolic process	1
heparan sulfate proteoglycan metabolic process	1
proteoglycan metabolic process	1
chondroitin sulfate proteoglycan metabolic process	1
dermatan sulfate proteoglycan metabolic process	1
heparan sulfate proteoglycan biosynthetic process	1
heparin proteoglycan biosynthetic process	1
chondroitin sulfate proteoglycan biosynthetic process	1
dermatan sulfate proteoglycan biosynthetic process	1
aminoglycan metabolic process	1
UDP-glycosyltransferase activity	1
galactosyltransferase activity	1
UDP-galactosyltransferase activity	1
catalytic activity, acting on a glycoprotein	1
catalytic activity	1
transferase activity	1
glycosyltransferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
organelle membrane	1

Protein interactions and networks

STRING

684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
B3GALT6	B4GALT7	Q9UBV7	880
B3GALT6	B3GAT3	O94766	816
B3GALT6	XYLT1	Q86Y38	804
B3GALT6	XYLT2	Q9H1B5	788
B3GALT6	FAM20B	O75063	699
B3GALT6	CHST14	Q8NCH0	691
B3GALT6	DSE	Q9UL01	621
B3GALT6	EXTL3	O43909	618
B3GALT6	FKBP14	Q9NWM8	605
B3GALT6	SLC39A13	Q96H72	599
B3GALT6	EXTL2	Q9UBQ6	596
B3GALT6	EXT2	Q93063	585
B3GALT6	EXT1	Q16394	555
B3GALT6	CSGALNACT1	Q8TDX6	548
B3GALT6	CHSY1	Q86X52	547

IntAct

54 interactions, top by confidence:

A	B	Type	Score
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
KCNA10	GAPDHS	psi-mi:“MI:0914”(association)	0.530
SCN3B	ABCC5	psi-mi:“MI:0914”(association)	0.530
PEX19	FAM20B	psi-mi:“MI:0914”(association)	0.530
PBXIP1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
PBXIP1	KCNN4	psi-mi:“MI:0914”(association)	0.530
HADHA	GPC4	psi-mi:“MI:0914”(association)	0.530
CD44	PDPK1	psi-mi:“MI:0914”(association)	0.530
	B3GALT6	psi-mi:“MI:0414”(enzymatic reaction)	0.440
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
SYNE4	GOLIM4	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350
SAAL1	QSOX1	psi-mi:“MI:0914”(association)	0.350
EIF2B5	GOLIM4	psi-mi:“MI:0914”(association)	0.350
SCN3B	A2ML1	psi-mi:“MI:0914”(association)	0.350
ATP2A3	UBXN8	psi-mi:“MI:0914”(association)	0.350
SPPL2B	HAS3	psi-mi:“MI:0914”(association)	0.350
CYP2C18	PGRMC1	psi-mi:“MI:0914”(association)	0.350
EIF2B5	KCNN4	psi-mi:“MI:0914”(association)	0.350
HADHA	AP3B1	psi-mi:“MI:0914”(association)	0.350

BioGRID (59): B3GALT6 (Affinity Capture-MS), B3GALT6 (Affinity Capture-MS), B3GALT6 (Affinity Capture-MS), B3GALT6 (Affinity Capture-MS), B3GALT6 (Affinity Capture-MS), B3GALT6 (Affinity Capture-MS), B3GALT6 (Two-hybrid), B3GALT6 (Affinity Capture-RNA), B3GALT6 (Affinity Capture-MS), B3GALT6 (Affinity Capture-MS), B3GALT6 (Proximity Label-MS), B3GALT6 (Proximity Label-MS), B3GALT6 (Negative Genetic), B3GALT6 (Affinity Capture-MS), B3GALT6 (Proximity Label-MS)

ESM2 similar proteins: A1A4L8, A1A4Q9, A1L134, A2BDX3, A5YM72, A6H707, B0BLZ5, B0JZP3, G3MZR2, O43292, O60831, O89109, P70295, Q11130, Q2TBP5, Q2V8X7, Q32NY4, Q3UPE3, Q4R4E4, Q4R4I9, Q5XIE1, Q5ZIW1, Q66HR0, Q6IQX7, Q6NRK8, Q6P2H8, Q7L1V2, Q80ZW2, Q86VU5, Q8IZ52, Q8N3Y3, Q8NE01, Q8NF37, Q8NI29, Q8TAC2, Q8TCD5, Q8TD43, Q8WUY1, Q92839, Q96DE0

Diamond homologs: A7XDQ9, Q6NRQ1, Q8BG28, Q8GXG6, Q8L7F9, Q8NCR0, Q8RX55, Q91Z92, Q96L58, Q9ASW1, Q9LV16, A8MXE2, O54904, O75752, O88178, O96024, Q1RLK6, Q3USF0, Q5RAL7, Q5TJE8, Q5XJP0, Q6AY39, Q6ZMB0, Q793U7, Q7JK24, Q7JK25, Q7JK26, Q7Z7M8, Q864U6, Q8R3I9, Q920V1, Q9BYG0, Q9C0J1, Q9MYM7, Q9N293, Q9N294, Q9N295, Q9Y2C3, Q9Y5Z6, Q9Z0F0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Metal ion SLC transporters	6	66.8×	9e-08
Glycosaminoglycan-protein linkage region biosynthesis	5	36.5×	2e-05
Glycosaminoglycan metabolism	5	20.3×	1e-04
R-HSA-425366	5	16.8×	3e-04
Metabolism of carbohydrates and carbohydrate derivatives	5	11.1×	1e-03
SLC-mediated transmembrane transport	10	11.0×	4e-06
Transport of small molecules	12	5.6×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	8	86.4×	6e-12
intracellular zinc ion homeostasis	9	66.7×	4e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

414 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	8
Uncertain significance	230
Likely benign	114
Benign	0

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
2151860	NM_080605.4(B3GALT6):c.3G>A (p.Met1Ile)	Pathogenic
2925287	NM_080605.4(B3GALT6):c.235A>G (p.Thr79Ala)	Pathogenic
3250476	NM_080605.4(B3GALT6):c.1A>C (p.Met1Leu)	Pathogenic
3748105	NM_080605.4(B3GALT6):c.636C>G (p.Tyr212Ter)	Pathogenic
3750880	NM_080605.4(B3GALT6):c.521_528del (p.Glu174fs)	Pathogenic
3760089	NC_000001.11:g.1232202_1232288del	Pathogenic
3760396	NM_080605.4(B3GALT6):c.84C>G (p.Tyr28Ter)	Pathogenic
4784715	NM_080605.4(B3GALT6):c.460A>T (p.Lys154Ter)	Pathogenic
4785201	NM_080605.4(B3GALT6):c.251_257del (p.Arg84fs)	Pathogenic
4786019	NM_080605.4(B3GALT6):c.117dup (p.Arg40fs)	Pathogenic
4788955	NM_080605.4(B3GALT6):c.197_253del (p.Ala66_Arg84del)	Pathogenic
4791228	NM_080605.4(B3GALT6):c.577A>T (p.Lys193Ter)	Pathogenic
4819964	NM_080605.4(B3GALT6):c.1A>T (p.Met1Leu)	Pathogenic
522415	NM_080605.4(B3GALT6):c.556T>C (p.Phe186Leu)	Pathogenic
60486	NM_080605.4(B3GALT6):c.466G>A (p.Asp156Asn)	Pathogenic
60487	NM_080605.4(B3GALT6):c.899G>C (p.Cys300Ser)	Pathogenic
60488	NM_080605.4(B3GALT6):c.193A>G (p.Ser65Gly)	Pathogenic
60489	NM_080605.4(B3GALT6):c.200C>T (p.Pro67Leu)	Pathogenic
60495	NM_080605.4(B3GALT6):c.619G>C (p.Asp207His)	Pathogenic
60496	NM_080605.4(B3GALT6):c.649G>A (p.Gly217Ser)	Pathogenic
60497	NM_080605.4(B3GALT6):c.323_344del (p.Ala108fs)	Pathogenic
869983	NM_080605.4(B3GALT6):c.476C>A (p.Ser159Tyr)	Pathogenic
869985	NM_080605.4(B3GALT6):c.618C>G (p.Cys206Trp)	Pathogenic
996068	NM_080605.4(B3GALT6):c.227del (p.Ile76fs)	Pathogenic
1067539	NM_080605.4(B3GALT6):c.2T>A (p.Met1Lys)	Likely pathogenic
3352555	NM_080605.4(B3GALT6):c.913C>T (p.Gln305Ter)	Likely pathogenic
3361286	NM_080605.4(B3GALT6):c.425G>A (p.Trp142Ter)	Likely pathogenic
452846	NM_080605.4(B3GALT6):c.239G>A (p.Trp80Ter)	Likely pathogenic
4795165	NM_080605.4(B3GALT6):c.2T>G (p.Met1Arg)	Likely pathogenic
60492	NM_080605.4(B3GALT6):c.588del (p.Arg197fs)	Likely pathogenic

SpliceAI

33 predictions. Top by Δscore:

Variant	Effect	Δscore
1:1234744:T:TA	acceptor_gain	0.5400
1:1234746:G:C	acceptor_gain	0.4900
1:1233665:AAT:A	donor_gain	0.3900
1:1234588:T:A	acceptor_gain	0.3700
1:1234075:C:G	donor_gain	0.3300
1:1233002:G:GT	donor_gain	0.3200
1:1233666:A:G	donor_gain	0.3100
1:1233905:A:C	acceptor_gain	0.3100
1:1233907:G:C	acceptor_gain	0.3100
1:1234578:A:AG	acceptor_gain	0.3100
1:1234579:G:GG	acceptor_gain	0.3100
1:1233253:G:GT	donor_gain	0.3000
1:1234142:A:G	donor_gain	0.3000
1:1234143:G:GG	donor_gain	0.3000
1:1233254:G:T	donor_gain	0.2800
1:1233870:A:AG	acceptor_gain	0.2800
1:1233871:G:GG	acceptor_gain	0.2800
1:1234751:T:TA	acceptor_gain	0.2800
1:1234762:G:GC	acceptor_gain	0.2800
1:1233607:G:GA	donor_gain	0.2700
1:1233190:GC:G	donor_gain	0.2600
1:1233323:C:T	donor_gain	0.2600
1:1234579:GTTT:G	acceptor_gain	0.2500
1:1233453:TGG:T	donor_gain	0.2400
1:1233570:A:AG	acceptor_gain	0.2200
1:1233571:G:GG	acceptor_gain	0.2200
1:1233871:GT:G	acceptor_gain	0.2200
1:1233903:TGAAG:T	acceptor_gain	0.2200
1:1233529:C:A	acceptor_gain	0.2100
1:1233670:AACTC:A	donor_gain	0.2100

AlphaMissense

2065 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:1232740:G:C	K154N	0.999
1:1232740:G:T	K154N	0.999
1:1232751:A:T	D158V	0.999
1:1232754:C:T	S159F	0.999
1:1232831:T:C	F185L	0.999
1:1232833:C:A	F185L	0.999
1:1232833:C:G	F185L	0.999
1:1232887:G:C	W203C	0.999
1:1232887:G:T	W203C	0.999
1:1233000:A:T	E241V	0.999
1:1233002:G:C	D242H	0.999
1:1233003:A:C	D242A	0.999
1:1233003:A:G	D242G	0.999
1:1233003:A:T	D242V	0.999
1:1233063:T:C	F262S	0.999
1:1233089:T:A	C271S	0.999
1:1233090:G:C	C271S	0.999
1:1233176:T:A	C300S	0.999
1:1233177:G:C	C300S	0.999
1:1232683:G:C	K135N	0.998
1:1232683:G:T	K135N	0.998
1:1232745:A:T	D156V	0.998
1:1232757:T:C	F160S	0.998
1:1232822:T:G	Y182D	0.998
1:1232828:G:C	G184R	0.998
1:1232829:G:A	G184D	0.998
1:1232835:T:C	F186S	0.998
1:1232841:G:A	G188D	0.998
1:1232937:T:A	L220H	0.998
1:1233004:C:A	D242E	0.998

dbSNP variants (sampled 300 via entrez): RS1000217585 (1:1235260 C>G,T), RS1000366062 (1:1234480 A>G), RS1000497910 (1:1234131 G>A,T), RS1000550182 (1:1234432 C>G), RS1000779379 (1:1231531 A>C), RS1001635716 (1:1233580 C>G,T), RS1001939919 (1:1231778 G>A), RS1002001561 (1:1233751 G>A,T), RS1002165554 (1:1233330 C>G,T), RS1002372560 (1:1231578 C>T), RS1002911404 (1:1232437 G>A,T), RS1004335865 (1:1233515 G>A), RS1004549168 (1:1232838 C>A,G,T), RS1004604623 (1:1231571 C>G), RS1005068463 (1:1232686 G>A)

Disease associations

OMIM: gene MIM:615291 | disease phenotypes: MIM:615349, MIM:271640, MIM:615593, MIM:609465

GenCC curated gene-disease

Disease	Classification	Inheritance
Ehlers-Danlos syndrome, spondylodysplastic type, 2	Definitive	Autosomal recessive
B3GALT6-congenital disorder of glycosylation	Definitive	Autosomal recessive
spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures	Definitive	Autosomal recessive
spondyloepimetaphyseal dysplasia with joint laxity	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
B3GALT6-congenital disorder of glycosylation	Definitive	AR

Mondo (7): Ehlers-Danlos syndrome, spondylodysplastic type, 2 (MONDO:0014139), spondyloepimetaphyseal dysplasia with joint laxity (MONDO:0019675), spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures (MONDO:0010075), combined immunodeficiency due to OX40 deficiency (MONDO:0014268), Al-Gazali syndrome (MONDO:0012282), B3GALT6-congenital disorder of glycosylation (MONDO:0100586), spondyloepiphyseal dysplasia (MONDO:0016761)

Orphanet (8): B3GALT6-related spondylodysplastic Ehlers-Danlos syndrome (Orphanet:536467), B4GALT7-related spondylodysplastic Ehlers-Danlos syndrome (Orphanet:75496), Combined immunodeficiency due to OX40 deficiency (Orphanet:431149), Spondyloepimetaphyseal dysplasia with joint laxity, Beighton type (Orphanet:642099), OBSOLETE: Spondyloepimetaphyseal dysplasia with joint laxity (Orphanet:93359), Spondyloepiphyseal dysplasia and spondyloepimetaphyseal dysplasia (Orphanet:253), Eye defects-arachnodactyly-cardiopathy syndrome (Orphanet:2725), OBSOLETE: Spondyloepimetaphyseal dysplasia (Orphanet:252)

HPO phenotypes

157 total (30 of 157 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000126	Hydronephrosis
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000272	Malar flattening
HP:0000300	Oval face
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000410	Mixed hearing impairment
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000473	Torticollis
HP:0000482	Microcornea
HP:0000501	Glaucoma
HP:0000520	Proptosis
HP:0000545	Myopia
HP:0000592	Blue sclerae
HP:0000647	Sclerocornea
HP:0000670	Carious teeth
HP:0000691	Microdontia
HP:0000703	Dentinogenesis imperfecta
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000878	11 pairs of ribs
HP:0000887	Cupped ribs
HP:0000904	Flaring of rib cage

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_1824	Blood protein levels	6.000000e-11

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C536817	Al-Gazali Syndrome (supp.)
C562968	Spondyloepimetaphyseal Dysplasia With Joint Laxity (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

41 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
bisphenol A	decreases expression	1
butyraldehyde	decreases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
pyrimidifen	decreases expression	1
ICG 001	affects expression	1
abrine	decreases expression	1
pyrachlostrobin	decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
picoxystrobin	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Antimycin A	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Carbamazepine	affects expression	1
Curcumin	increases expression	1
Doxorubicin	decreases expression	1
Gallic Acid	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.