B4GALT7

Summary

B4GALT7 (beta-1,4-galactosyltransferase 7, HGNC:930) is a protein-coding gene on chromosome 5q35.3, encoding Beta-1,4-galactosyltransferase 7 (Q9UBV7). Required for the biosynthesis of the tetrasaccharide linkage region of proteoglycans, especially for small proteoglycans in skin fibroblasts.

This gene is a member of the beta-1,4-galactosyltransferase (beta4GalT) family. Family members encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose. Each beta4GalT member has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus which then remains uncleaved to function as a transmembrane anchor. The enzyme encoded by this gene attaches the first galactose in the common carbohydrate-protein linkage (GlcA-beta1,3-Gal-beta1,3-Gal-beta1,4-Xyl-beta1-O-Ser) found in proteoglycans. This enzyme differs from other beta4GalTs because it lacks the conserved Cys residues found in beta4GalT1-beta4GalT6 and it is located in cis-Golgi instead of trans-Golgi. Mutations in this gene have been associated with the progeroid form of Ehlers-Danlos syndrome.

Source: NCBI Gene 11285 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Ehlers-Danlos syndrome, spondylodysplastic type, 1 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 462 total — 21 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 75
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_007255

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:930
Approved symbol	B4GALT7
Name	beta-1,4-galactosyltransferase 7
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Aliases	XGALT-1, beta4Gal-T7
Ensembl gene	ENSG00000027847
Ensembl biotype	protein_coding
OMIM	604327
Entrez	11285

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000029410, ENST00000502420, ENST00000505145, ENST00000505433, ENST00000505468, ENST00000507061, ENST00000510761, ENST00000515353, ENST00000871348, ENST00000871349, ENST00000871350, ENST00000920069, ENST00000966181, ENST00000966182, ENST00000966183, ENST00000966184

RefSeq mRNA: 1 — MANE Select: NM_007255 NM_007255

CCDS: CCDS4429

Canonical transcript exons

ENST00000029410 — 6 exons

Exon	Start	End
ENSE00001194962	177607302	177607527
ENSE00001301765	177609540	177610330
ENSE00001325209	177600132	177600260
ENSE00003554574	177608539	177608622
ENSE00003624970	177604179	177604541
ENSE00003659112	177608910	177609014

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 94.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.5956 / max 74.9255, expressed in 1804 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60504	15.5956	1804

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	94.11	gold quality
right adrenal gland	UBERON:0001233	93.77	gold quality
left adrenal gland	UBERON:0001234	93.44	gold quality
left adrenal gland cortex	UBERON:0035825	93.22	gold quality
right adrenal gland cortex	UBERON:0035827	93.00	gold quality
adenohypophysis	UBERON:0002196	92.60	gold quality
adrenal cortex	UBERON:0001235	91.91	gold quality
apex of heart	UBERON:0002098	91.88	gold quality
body of pancreas	UBERON:0001150	91.80	gold quality
adrenal gland	UBERON:0002369	91.03	gold quality
pituitary gland	UBERON:0000007	91.02	gold quality
stromal cell of endometrium	CL:0002255	90.54	gold quality
body of stomach	UBERON:0001161	90.15	gold quality
right ovary	UBERON:0002118	89.78	gold quality
right lobe of thyroid gland	UBERON:0001119	89.72	gold quality
left ovary	UBERON:0002119	89.41	gold quality
right lobe of liver	UBERON:0001114	89.37	gold quality
left uterine tube	UBERON:0001303	89.31	gold quality
granulocyte	CL:0000094	89.28	gold quality
right testis	UBERON:0004534	89.07	gold quality
metanephros cortex	UBERON:0010533	89.06	gold quality
left testis	UBERON:0004533	88.85	gold quality
right atrium auricular region	UBERON:0006631	88.72	gold quality
ectocervix	UBERON:0012249	88.68	gold quality
body of uterus	UBERON:0009853	88.66	gold quality
left lobe of thyroid gland	UBERON:0001120	88.56	gold quality
right uterine tube	UBERON:0001302	88.47	gold quality
endocervix	UBERON:0000458	88.41	gold quality
spleen	UBERON:0002106	88.40	gold quality
gastrocnemius	UBERON:0001388	88.22	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.13
E-HCAD-5	no	2.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting B4GALT7, 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-4533	100.00	69.48	2758
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-382-3P	98.83	67.10	1074
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-4690-3P	97.02	64.72	981
HSA-MIR-5586-5P	96.29	68.02	685
HSA-MIR-6735-3P	96.10	63.81	600
HSA-MIR-6823-3P	95.45	66.14	704
HSA-MIR-604	93.13	64.42	299

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 13)

• phosphorylation of Xyl on the C-2 position prevents GalT-I activity (PMID:15522873)
• reduced beta4GalT-7 activity resulting in defective glycosylation of decorin and biglycan may be responsible for the complex molecular pathology in beta4GalT-7 deficient Ehlers-Danlos syndrome patients (PMID:16583246)
• Study suggests an heparan sulfate-dependent basic mechanism behind the altered wound repair phenotype of beta4GalT-7-deficient Ehlers-Danlos syndrome patients. (PMID:18158310)
• This study establishes the molecular basis for beta4GalT7 defects associated with altered GAG synthesis in Ehlers-Danlos syndrome. (PMID:20691685)
• Mutated ennzyme affects glycosaminoglycan synthesis and is involved Ehlers-Danlos syndrome. (PMID:20809901)
• Two evolutionary conserved motifs, (163)DVD(165) and (221)FWGWGREDDE(230), are central in the organization of the enzyme active site. (PMID:20843813)
• a Michaelis complex of a glycosyltransferase has been described, and it clearly suggests an SN2 type catalytic mechanism for the beta4GalT7 enzyme. (PMID:24052259)
• Our findings demonstrate that B4GALT7 is the causative gene for LRS. The identification of a unique homozygous mutation argues in favor of a founder effect. B4GALT7 encodes a galactosyltransferase. (PMID:24755949)
• identified two key structural features forming stacking interactions with the aglycone, and the hydrogen bond between the His(195) nitrogen backbone and the carbonyl group of the coumarinyl molecule to develop a tight binder of hbeta4GalT7 (PMID:25568325)
• The phenotypes described in this article caused by bi-allelic mutations in B4GALT7 would benefit from reclassification and loss of its current association with PEDS. These conditions would be better grouped with the other linkeropathies. (PMID:26940150)
• The findings in this family expand the clinical phenotype of B4GALT7-related linkeropathies to include perinatal lethal skeletal dysplasia (PMID:31278392)
• Define 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)
• Targeting B4GALT7 suppresses the proliferation, migration and invasion of hepatocellular carcinoma through the Cdc2/CyclinB1 and miR-338-3p/MMP2 pathway. (PMID:38025683)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	b4galt7	ENSDARG00000021899
mus_musculus	B4galt7	ENSMUSG00000021504
rattus_norvegicus	B4galt7	ENSRNOG00000021886
drosophila_melanogaster	beta4GalT7	FBGN0039258
caenorhabditis_elegans		WBGENE00005021

Paralogs (6): B4GALT1 (ENSG00000086062), B4GALT2 (ENSG00000117411), B4GALT6 (ENSG00000118276), B4GALT4 (ENSG00000121578), B4GALT5 (ENSG00000158470), B4GALT3 (ENSG00000158850)

Protein

Protein identifiers

Beta-1,4-galactosyltransferase 7 — Q9UBV7 (reviewed: Q9UBV7)

Alternative names: Proteoglycan UDP-galactose:beta-xylose beta1,4-galactosyltransferase I, UDP-Gal:beta-GlcNAc beta-1,4-galactosyltransferase 7, UDP-galactose:beta-N-acetylglucosamine beta-1,4-galactosyltransferase 7, UDP-galactose:beta-xylose beta-1,4-galactosyltransferase, XGPT, XGalT-1, Xylosylprotein 4-beta-galactosyltransferase, Xylosylprotein beta-1,4-galactosyltransferase

All UniProt accessions (5): D6RA33, D6RDJ8, D6RJI5, Q9UBV7, H0Y9D6

UniProt curated annotations — full annotation on UniProt →

Function. Required for the biosynthesis of the tetrasaccharide linkage region of proteoglycans, especially for small proteoglycans in skin fibroblasts.

Subcellular location. Golgi apparatus. Golgi stack membrane.

Tissue specificity. High expression in heart, pancreas and liver, medium in placenta and kidney, low in brain, skeletal muscle and lung.

Disease relevance. Ehlers-Danlos syndrome, spondylodysplastic type, 1 (EDSSPD1) [MIM:130070] A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSSPD1 is an autosomal recessive form characterized by short stature, developmental anomalies of the forearm bones and elbow, and bowing of extremities, in addition to the classic features of Ehlers-Danlos syndrome. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 7 family.

RefSeq proteins (1): NP_009186* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003859	Galactosyl_T	Family
IPR027791	Galactosyl_T_C	Domain
IPR027995	Galactosyl_T_N	Domain
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily

Pfam: PF02709, PF13733

Enzyme classification (BRENDA):

• EC 2.4.1.133 — xylosylprotein 4-beta-galactosyltransferase (BRENDA: 8 organisms, 83 substrates, 23 inhibitors, 137 Km, 56 kcat entries)
• EC 2.4.1.38 — beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase (BRENDA: 18 organisms, 205 substrates, 71 inhibitors, 132 Km, 51 kcat entries)

Substrate kinetics (BRENDA)

68 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UDP-GALACTOSE	0.02–2.41	42
4-METHYLUMBELLIFERYL-BETA-D-XYLOPYRANOSIDE	0.16–4.22	29
N-ACETYLGLUCOSAMINE	0.0007–40	27
UDPGALACTOSE	0.0108–0.25	26
4-METHYLUMBELLIFERYL O-BETA-D-XYLOPYRANOSIDE	0.27–4.22	10
4-NITROPHENYL-BETA-D-XYLOPYRANOSIDE	0.85–7.93	10
UDP-ALPHA-D-GALACTOSE	0.22–0.4	10
4-METHYLUMBELLIFERYL-BETA-D-XYLOPYRANOSIDE	0.35–1.06	10
UDP-GALACTOSE	0.0105–0.31	5
UDP-GLUCOSE	0.031–0.28	5
4-NITROPHENYL O-BETA-D-XYLOPYRANOSIDE	1.27–7.93	4
UDPGALACTOSE	0.05–0.41	4
D-GLUCOSE	1–21	4
4-METHYLUMBELLIFERYL-BETA-D-XYLOSIDE	0.33–0.5	2

Catalyzed reactions (Rhea), 1 shown:

• 3-O-(beta-D-xylosyl)-L-seryl-[protein] + UDP-alpha-D-galactose = 3-O-(beta-D-galactosyl-(1->4)-beta-D-xylosyl)-L-seryl-[protein] + UDP + H(+) (RHEA:15297)

UniProt features (45 total): strand 12, binding site 10, helix 9, turn 4, topological domain 2, sequence variant 2, chain 1, glycosylation site 1, disulfide bond 1, sequence conflict 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4IRP	X-RAY DIFFRACTION	2.1
4IRQ	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBV7-F1	88.70	0.76

Functional residue map

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

Ligand- & substrate-binding residues (10): 224; 226–229; 257–259; 257; 266; 100–104; 139–141; 164–165; 165; 194

Disulfide bonds (1): 316–324

Glycosylation sites (1): 154

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-1971475	Glycosaminoglycan-protein linkage region biosynthesis
R-HSA-3560783	Defective B4GALT7 causes EDS, progeroid type
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: 306 (showing top): AGGAAGC_MIR5163P, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, GOBP_NEGATIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_AMINOGLYCAN_BIOSYNTHETIC_PROCESS, GOBP_CHONDROITIN_SULFATE_PROTEOGLYCAN_BIOSYNTHETIC_PROCESS, GOBP_HEPARAN_SULFATE_PROTEOGLYCAN_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, VANHARANTA_UTERINE_FIBROID_WITH_7Q_DELETION_DN, GOBP_AMINOGLYCAN_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, GOBP_CHONDROITIN_SULFATE_PROTEOGLYCAN_METABOLIC_PROCESS, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS

GO Biological Process (12): carbohydrate metabolic process (GO:0005975), glycosaminoglycan biosynthetic process (GO:0006024), proteoglycan metabolic process (GO:0006029), protein N-linked glycosylation (GO:0006487), proteoglycan biosynthetic process (GO:0030166), protein modification process (GO:0036211), negative regulation of fibroblast proliferation (GO:0048147), supramolecular fiber organization (GO:0097435), glycosaminoglycan-protein linkage region biosynthetic process (GO:0120532), obsolete protein glycosylation (GO:0006486), glycosaminoglycan metabolic process (GO:0030203), obsolete glycosylation (GO:0070085)

GO Molecular Function (8): beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase activity (GO:0003831), galactosyltransferase activity (GO:0008378), manganese ion binding (GO:0030145), xylosylprotein 4-beta-galactosyltransferase activity (GO:0046525), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), metal ion binding (GO:0046872)

GO Cellular Component (5): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), membrane (GO:0016020), Golgi cisterna membrane (GO:0032580), endomembrane system (GO:0012505)

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
glycoprotein biosynthetic process	2
UDP-galactosyltransferase activity	2
cellular anatomical structure	2
primary metabolic process	1
aminoglycan biosynthetic process	1
glycosaminoglycan metabolic process	1
glycoprotein metabolic process	1
proteoglycan metabolic process	1
protein metabolic process	1
macromolecule modification	1
negative regulation of cell population proliferation	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
cellular component organization	1
heparan sulfate proteoglycan biosynthetic process	1
heparin proteoglycan biosynthetic process	1
chondroitin sulfate proteoglycan biosynthetic process	1
dermatan sulfate proteoglycan biosynthetic process	1
protein O-linked glycosylation via xylose	1
aminoglycan metabolic process	1
hexosyltransferase activity	1
transition metal ion binding	1
catalytic activity, acting on a glycoprotein	1
binding	1
catalytic activity	1
transferase activity	1
cation binding	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
Golgi cisterna	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1438 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
B4GALT7	B3GALT6	Q96L58	880
B4GALT7	B3GAT3	O94766	864
B4GALT7	XYLT2	Q9H1B5	797
B4GALT7	XYLT1	Q86Y38	797
B4GALT7	CHST14	Q8NCH0	716
B4GALT7	EXTL3	O43909	688
B4GALT7	SLC35B2	Q8TB61	686
B4GALT7	FAM20B	O75063	672
B4GALT7	EXT2	Q93063	668
B4GALT7	CSGALNACT1	Q8TDX6	665
B4GALT7	CHSY1	Q86X52	662
B4GALT7	CSGALNACT2	Q8N6G5	656
B4GALT7	EXT1	Q16394	645
B4GALT7	SLC39A13	Q96H72	641
B4GALT7	FKBP14	Q9NWM8	625

IntAct

111 interactions, top by confidence:

A	B	Type	Score
EZR	MSN	psi-mi:“MI:0914”(association)	0.740
RABGGTB	B4GALT7	psi-mi:“MI:0915”(physical association)	0.720
B4GALT7	RABGGTB	psi-mi:“MI:0915”(physical association)	0.720
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
B4GALT7		psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	B4GALT7	psi-mi:“MI:0915”(physical association)	0.560
	B4GALT7	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	B4GALT7	psi-mi:“MI:0915”(physical association)	0.560
KRT31	B4GALT7	psi-mi:“MI:0915”(physical association)	0.560
TMEM14B	B4GALT7	psi-mi:“MI:0915”(physical association)	0.560
PCNA	POM121C	psi-mi:“MI:0914”(association)	0.550
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
GAA	B3GAT3	psi-mi:“MI:0914”(association)	0.530
YIPF3	TMEM120B	psi-mi:“MI:0914”(association)	0.530
TMEM192	STXBP3	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
FUT1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
B4GAT1	ADCY6	psi-mi:“MI:0914”(association)	0.530
GINM1	ADCY9	psi-mi:“MI:0914”(association)	0.530
EDA	AP3B1	psi-mi:“MI:0914”(association)	0.530
B4GALT7	HSPA5	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (96): B4GALT7 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-3 (Two-hybrid), B4GALT7 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), B4GALT7 (Affinity Capture-MS), B4GALT7 (Affinity Capture-MS), B4GALT7 (Affinity Capture-MS), B4GALT7 (Affinity Capture-MS), B4GALT7 (Affinity Capture-MS), B4GALT7 (Affinity Capture-MS), B4GALT7 (Affinity Capture-MS), B4GALT7 (Affinity Capture-MS), B4GALT7 (Affinity Capture-MS), B4GALT7 (Affinity Capture-MS)

ESM2 similar proteins: A5D7I4, A5PK45, A7MB73, A9X1C8, O09009, O09010, O12971, O12972, O60568, O97583, P16442, P52848, P52849, P52850, P97464, Q02353, Q16394, Q2KJ92, Q3UHN9, Q5IGR7, Q5IGR8, Q5R6K5, Q5RBC3, Q5T4B2, Q5U367, Q5U4X8, Q6GQK9, Q6IS24, Q6ZQ11, Q6ZRP7, Q7Z4H8, Q812F8, Q86X52, Q8K297, Q8NBJ5, Q8NES3, Q8R087, Q8VHI3, Q924T4, Q9EQH7

Diamond homologs: A0A1S6M251, A8Y1P7, O43286, O60512, O60513, O60909, O88419, P08037, P15291, P15535, P34548, Q09323, Q3YL68, Q5EA87, Q5NVN3, Q66HH1, Q6P768, Q80WN7, Q80WN8, Q80WN9, Q8R087, Q91YY2, Q9GUM2, Q9JJ04, Q9JMK0, Q9UBV7, Q9UBX8, Q9VBZ9, Q9WVK5, Q9Z2Y2, Q6ZQ11, Q86X52

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	7
Uncertain significance	210
Likely benign	173
Benign	22

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
1354563	NM_007255.3(B4GALT7):c.225C>A (p.Cys75Ter)	Pathogenic
1406837	NM_007255.3(B4GALT7):c.325del (p.Leu109fs)	Pathogenic
154471	GRCh38/hg38 5q35.2-35.3(chr5:176517339-177709289)x1	Pathogenic
2165476	NM_007255.3(B4GALT7):c.242_243del (p.Pro81fs)	Pathogenic
225691	NM_007255.3(B4GALT7):c.122T>C (p.Leu41Pro)	Pathogenic
2424617	NC_000005.9:g.(?176289625)(177151363_?)del	Pathogenic
3062841	GRCh37/hg19 5q35.2-35.3(chr5:176385815-178410738)x1	Pathogenic
4759179	NM_007255.3(B4GALT7):c.579_580del (p.Tyr194fs)	Pathogenic
4759187	NM_007255.3(B4GALT7):c.474_475del (p.Ile159fs)	Pathogenic
4759191	NM_007255.3(B4GALT7):c.118_119del (p.Ser40fs)	Pathogenic
4759192	NM_007255.3(B4GALT7):c.39G>A (p.Trp13Ter)	Pathogenic
4769041	NM_007255.3(B4GALT7):c.230dup (p.Glu78fs)	Pathogenic
4771301	NM_007255.3(B4GALT7):c.397C>T (p.Gln133Ter)	Pathogenic
4773076	NM_007255.3(B4GALT7):c.276_277dup (p.His93fs)	Pathogenic
4799475	NM_007255.3(B4GALT7):c.99_100insGA (p.Leu34fs)	Pathogenic
4808196	NM_007255.3(B4GALT7):c.678_679del (p.Glu227fs)	Pathogenic
4810085	NM_007255.3(B4GALT7):c.448dup (p.Leu150fs)	Pathogenic
4847121	NM_007255.3(B4GALT7):c.90del (p.Val31fs)	Pathogenic
4847371	NC_000005.9:g.(?177027132)(177027262_177031179)del	Pathogenic
5612	NM_007255.3(B4GALT7):c.617T>C (p.Leu206Pro)	Pathogenic
5613	NM_007255.3(B4GALT7):c.808C>T (p.Arg270Cys)	Pathogenic
1340213	GRCh37/hg19 5q35.2-35.3(chr5:176497464-177776599)x3	Likely pathogenic
1808750	GRCh37/hg19 5q35.2-35.3(chr5:176516440-177773252)x3	Likely pathogenic
2064958	NM_007255.3(B4GALT7):c.414-2A>G	Likely pathogenic
2129648	NM_007255.3(B4GALT7):c.179_413+354del	Likely pathogenic
2179225	NM_007255.3(B4GALT7):c.50+1G>A	Likely pathogenic
4771556	NM_007255.3(B4GALT7):c.639+1G>A	Likely pathogenic
5611	NM_007255.3(B4GALT7):c.557C>A (p.Ala186Asp)	Likely pathogenic

SpliceAI

1482 predictions. Top by Δscore:

Variant	Effect	Δscore
5:177604539:CAG:C	donor_loss	1.0000
5:177604541:GGT:G	donor_loss	1.0000
5:177607524:GCTG:G	donor_gain	1.0000
5:177607528:G:GG	donor_gain	1.0000
5:177608537:A:AG	acceptor_gain	1.0000
5:177608538:G:GA	acceptor_gain	1.0000
5:177608618:TCCAG:T	donor_loss	1.0000
5:177608619:CCAGG:C	donor_loss	1.0000
5:177608620:CAGGT:C	donor_loss	1.0000
5:177608621:AGG:A	donor_loss	1.0000
5:177608622:GG:G	donor_loss	1.0000
5:177608623:G:C	donor_loss	1.0000
5:177608624:T:A	donor_loss	1.0000
5:177608812:G:GT	donor_gain	1.0000
5:177608904:CCCTA:C	acceptor_loss	1.0000
5:177608905:CCTA:C	acceptor_loss	1.0000
5:177608906:CTAGC:C	acceptor_loss	1.0000
5:177608907:TA:T	acceptor_loss	1.0000
5:177608908:A:AG	acceptor_gain	1.0000
5:177608908:AG:A	acceptor_loss	1.0000
5:177608909:G:GG	acceptor_gain	1.0000
5:177608909:GC:G	acceptor_gain	1.0000
5:177608909:GCT:G	acceptor_gain	1.0000
5:177608909:GCTT:G	acceptor_gain	1.0000
5:177609010:AACAG:A	donor_loss	1.0000
5:177609011:ACAG:A	donor_loss	1.0000
5:177609012:CAG:C	donor_loss	1.0000
5:177609013:AGGTG:A	donor_loss	1.0000
5:177609014:GG:G	donor_loss	1.0000
5:177609016:T:A	donor_loss	1.0000

AlphaMissense

2139 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:177607303:T:C	F139L	1.000
5:177607305:C:A	F139L	1.000
5:177607305:C:G	F139L	1.000
5:177607376:A:C	D163A	1.000
5:177607376:A:T	D163V	1.000
5:177608569:T:A	W224R	1.000
5:177608569:T:C	W224R	1.000
5:177608571:G:C	W224C	1.000
5:177608571:G:T	W224C	1.000
5:177608579:A:T	E227V	1.000
5:177608581:G:C	D228H	1.000
5:177608582:A:C	D228A	1.000
5:177608582:A:T	D228V	1.000
5:177604541:G:T	R138M	0.999
5:177607326:C:A	N146K	0.999
5:177607326:C:G	N146K	0.999
5:177607376:A:G	D163G	0.999
5:177607377:C:A	D163E	0.999
5:177607377:C:G	D163E	0.999
5:177607382:A:T	D165V	0.999
5:177607385:T:C	L166P	0.999
5:177608545:G:T	G216W	0.999
5:177608546:G:A	G216E	0.999
5:177608546:G:T	G216V	0.999
5:177608560:T:C	F221L	0.999
5:177608562:C:A	F221L	0.999
5:177608562:C:G	F221L	0.999
5:177608563:T:A	W222R	0.999
5:177608563:T:C	W222R	0.999
5:177608565:G:C	W222C	0.999

dbSNP variants (sampled 300 via entrez): RS1000152141 (5:177599207 G>A,C), RS1000236406 (5:177606515 A>AG), RS1000244469 (5:177598876 A>G), RS1000493198 (5:177604766 A>C,G), RS1000497260 (5:177600097 G>A,C), RS1000585421 (5:177606260 C>T), RS1000693890 (5:177606110 G>A,C), RS1000759725 (5:177604923 C>T), RS1001191985 (5:177605132 C>T), RS1001201480 (5:177599708 A>T), RS1001251883 (5:177600011 G>A), RS1001357111 (5:177604025 A>C,T), RS1002662213 (5:177598453 A>G), RS1002887442 (5:177606487 C>T), RS1003759813 (5:177607884 T>G)

Disease associations

OMIM: gene MIM:604327 | disease phenotypes: MIM:130000, MIM:130070, MIM:117550, MIM:245600, MIM:127550

GenCC curated gene-disease

Disease	Classification	Inheritance
Ehlers-Danlos syndrome, spondylodysplastic type, 1	Definitive	Autosomal recessive
Ehlers-Danlos syndrome, spondylodysplastic type	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Ehlers-Danlos syndrome, spondylodysplastic type, 1	Definitive	AR

Mondo (7): Ehlers-Danlos syndrome, spondylodysplastic type (MONDO:0007526), Ehlers-Danlos syndrome (MONDO:0020066), Ehlers-Danlos syndrome, spondylodysplastic type, 1 (MONDO:0020682), spondylodysplastic Ehlers-Danlos syndrome (MONDO:0034021), Sotos syndrome (MONDO:0019349), Larsen-like syndrome, B3GAT3 type (MONDO:0009511), dyskeratosis congenita (MONDO:0015780)

Orphanet (6): B4GALT7-related spondylodysplastic Ehlers-Danlos syndrome (Orphanet:75496), Ehlers-Danlos syndrome (Orphanet:98249), Spondylodysplastic Ehlers-Danlos syndrome (Orphanet:536471), Sotos syndrome (Orphanet:821), Larsen-like syndrome, B3GAT3 type (Orphanet:284139), Dyskeratosis congenita (Orphanet:1775)

HPO phenotypes

75 total (30 of 75 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000230	Gingivitis
HP:0000256	Macrocephaly
HP:0000274	Small face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000387	Absent earlobe
HP:0000431	Wide nasal bridge
HP:0000506	Telecanthus
HP:0000520	Proptosis
HP:0000540	Hypermetropia
HP:0000592	Blue sclerae
HP:0000653	Sparse eyelashes
HP:0000768	Pectus carinatum
HP:0000774	Narrow chest
HP:0000894	Short clavicles
HP:0000938	Osteopenia
HP:0000954	Single transverse palmar crease
HP:0000963	Thin skin
HP:0000973	Cutis laxa
HP:0000974	Hyperextensible skin
HP:0000987	Atypical scarring of skin
HP:0001000	Abnormality of skin pigmentation

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004136_23	Methadone dose in opioid dependence	4.000000e-06
GCST005956_15	Waist-to-hip ratio adjusted for BMI	1.000000e-07
GCST005957_13	Waist-to-hip ratio adjusted for BMI (age <50)	3.000000e-07
GCST005962_42	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-08
GCST006585_2590	Blood protein levels	5.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007907	methadone dose measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D019871	Dyskeratosis Congenita	C15.378.190.223.500.750; C16.131.831.150; C16.320.322.108; C16.320.850.235; C17.800.804.150; C17.800.827.235
D004535	Ehlers-Danlos Syndrome	C14.907.454.240; C15.378.463.515.240; C16.131.831.428; C16.320.850.260; C17.300.200.310; C17.800.804.428; C17.800.827.260
D058495	Sotos Syndrome	C16.131.077.889; C16.131.260.905; C16.320.180.905
C536201	Ehlers-Danlos syndrome, progeroid form (supp.)
C537874	Larsen syndrome, recessive type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects cotreatment, increases abundance	2
Cadmium	increases abundance, increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
cobaltous chloride	decreases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
ochratoxin A	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
ICG 001	increases expression	1
MT19c compound	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	increases expression	1
Resveratrol	increases expression, affects cotreatment, decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	affects expression	1
Cytarabine	decreases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Doxorubicin	increases expression	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
Indomethacin	increases expression, affects cotreatment	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Ozone	increases oxidation, increases abundance, affects cotreatment	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SE56	HAP1 B4GALT7 (-) 1	Cancer cell line	Male
CVCL_SE57	HAP1 B4GALT7 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04890431	PHASE4	UNKNOWN	Impact of Oxygen Therapy on Fatigue in Patients With Hypermobile-type Ehlers-Danlos Syndrome
NCT05603741	PHASE4	ACTIVE_NOT_RECRUITING	Local Anesthetic Response in Ehlers-Danlos Syndrome (EDS) and Healthy Volunteers
NCT05279937	PHASE3	NOT_YET_RECRUITING	The Ultrasound-Guided Dextrose Prolotherapy in Ehlers-Danlos Syndrome Patients
NCT00001966	PHASE2	COMPLETED	Mind-Body Therapy for Pain in Ehlers-Danlos Syndrome
NCT00004787	PHASE2	COMPLETED	Phase II Pilot Study of Granulocyte Colony-Stimulating Factor for Inherited Bone Marrow Failure Syndromes
NCT01659606	PHASE2	ACTIVE_NOT_RECRUITING	Radiation- and Alkylator-free Bone Marrow Transplantation Regimen for Patients With Dyskeratosis Congenita
NCT03579875	PHASE2	RECRUITING	Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
NCT04232085	PHASE2	RECRUITING	Regenerative Medicine to Restore Hematopoiesis and Immune Function in Immunodeficiencies and Inherited Bone Marrow Failures
NCT04638517	PHASE2	TERMINATED	The TELO-SCOPE Study: Attenuating Telomere Attrition With Danazol. Is There Scope to Dramatically Improve Health Outcomes for Adults and Children With Pulmonary Fibrosis
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT06477614	PHASE1	RECRUITING	Anti-cancer DC Cell Vaccination to Treat Solid Tumors
NCT06817590	PHASE1	RECRUITING	Nucleoside Therapy in Patients With Telomere Biology Disorders
NCT03686748	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Two Point Discrimination
NCT00001641	Not specified	COMPLETED	Study of Heritable Connective Tissue Disorders
NCT00270686	Not specified	COMPLETED	Studies of Heritable Disorders of Connective Tissue
NCT01322165	Not specified	COMPLETED	National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions
NCT01356134	Not specified	COMPLETED	Vascular Fundus Changes in Patients With High Probability of Chronic Cerebrospinal Venous Insufficiency (CCSVI)
NCT01367977	Not specified	COMPLETED	Head Circumference Growth in Children With Ehlers-Danlos Syndrome Who Develop Dysautonomia Later in Life
NCT02050113	Not specified	RECRUITING	Complex Aortic Aneurysm Repair Using Physician Modified Endografts and Custom Made Devices
NCT02435745	Not specified	COMPLETED	Obstructive Sleep Apnoea in Ehlers-Danlos Syndrome
NCT02721797	Not specified	UNKNOWN	Origins and Impact of EDS in Connective Tissues and Skin
NCT02985710	Not specified	COMPLETED	Assessment of Small Fiber Neuropathy in Rare Diseases Using Sudoscan
NCT03093493	Not specified	COMPLETED	Genetics of Ehlers-Danlos Syndrome
NCT03330977	Not specified	UNKNOWN	Efficiency Clinical Study of NOVATEX MEDICAL Compression Garments in Patients With Ehlers-Danlos Syndrome
NCT03575182	Not specified	UNKNOWN	Gait Retraining in Patients With Joint Hypermobility Syndrome/Hypermobile Ehlers Danlos Syndrome
NCT03596437	Not specified	UNKNOWN	Study of Arterial Properties by Ultra-high Frequency Ultrasound in Fibromuscular Dysplasia and Vascular Ehlers-Danlos Syndrome
NCT03602482	Not specified	COMPLETED	Standing Cognition and Co-morbidities of POTS Evaluation
NCT03681080	Not specified	COMPLETED	Concentration and Attentional Deficits in POTS and Other Autonomic Neuropathies
NCT03986229	Not specified	COMPLETED	Evaluation of the Effect of Custom Compression Garments on Standing Static Balance in Ehlers Danlos Syndrome
NCT04036305	Not specified	ACTIVE_NOT_RECRUITING	Local Anesthetic Response in Ehlers-Danlos Syndrome (EDS) and Healthy Volunteers
NCT04133272	Not specified	RECRUITING	Registry of Ehlers-Danlos Syndrome
NCT04437589	Not specified	COMPLETED	Opioid-Free Anesthesia for Patients With Joint Hypermobility Syndrome Undergoing Craneo-Cervical Fixation: A Case-series
NCT04680793	Not specified	COMPLETED	Effects of a Multidisciplinary Outpatient Rehabilitation Program in Patients With Ehlers-Danlos Syndrome.
NCT04734041	Not specified	COMPLETED	Integrative Medicine for Hypermobility Spectrum Disorder and Ehlers-Danlos Syndromes (IMforHSDandEDS)
NCT04742803	Not specified	COMPLETED	Straberi Epistamp Needling Treatment For Skin Rejuvenation
NCT04806620	Not specified	RECRUITING	Unhide® Project: A Digital Health Platform to Collect Lifestyle Data for Brain Inflammation Research
NCT05137379	Not specified	COMPLETED	Evaluation of a Cohort of Patients With Ehlers-Danlos Syndrome Treated With Orthopedic Surgery (SED-eval)
NCT05366114	Not specified	UNKNOWN	Vision-based Assessment of Joint Extensibility in Ehlers Danlos Syndrome
NCT05389865	Not specified	ACTIVE_NOT_RECRUITING	Proximal Aortopathy in Scotland - Epidemiology and Surgical Outcomes
NCT05429996	Not specified	UNKNOWN	Ultrastructural Collagen Markers in Ehlers Danlos Syndromes