B3GALT6

Chr 1AR

beta-1,3-galactosyltransferase 6

Also known as: ALGAZ, EDSP2, EDSSPD2, SEMDJL1, beta3GalT6

The protein is a beta-1,3-galactosyltransferase that catalyzes the transfer of galactose to substrates in glycosaminoglycan synthesis, particularly in the linker regions of heparan sulfate and chondroitin sulfate. Biallelic mutations cause autosomal recessive connective tissue disorders including Ehlers-Danlos syndrome spondylodysplastic type 2, spondyloepimetaphyseal dysplasia with joint laxity, and Al-Gazali syndrome. These conditions primarily affect the skeletal system and connective tissues, presenting with joint hypermobility, bone dysplasia, and variable developmental features.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Al-Gazali syndromeMIM #609465
AR
Ehlers-Danlos syndrome, spondylodysplastic type, 2MIM #615349
AR
Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fracturesMIM #271640
AR
0
Active trials
8
Pubs (1 yr)
134
P/LP submissions
15%
P/LP missense
1.43
LOEUF
LOF
Mechanism· G2P
Clinical SummaryB3GALT6
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Gene-Disease Validity (ClinGen)
B3GALT6-congenital disorder of glycosylation · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
113 unique Pathogenic / Likely Pathogenic· 225 VUS of 455 total submissions
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GeneReview available — B3GALT6
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.43LOEUF
pLI 0.023
Z-score 0.93
OE 0.56 (0.261.43)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.26Z-score
OE missense 0.69 (0.590.82)
93 obs / 134.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.56 (0.261.43)
00.351.4
Missense OE0.69 (0.590.82)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 3 / 5.3Missense obs/exp: 93 / 134.1Syn Z: 0.41
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveB3GALT6-related Ehlers-Danlos syndrome, spondylodysplastic typeOTHERAR
definitiveB3GALT6-related spondyloepimetaphyseal dysplasia with joint laxityLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6452th %ile
GOF
0.72top 25%
LOF
0.2678th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

455 submitted variants in ClinVar

Classification Summary

Pathogenic97
Likely Pathogenic16
VUS225
Likely Benign102
Conflicting15
97
Pathogenic
16
Likely Pathogenic
225
VUS
102
Likely Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
11
81
0
97
Likely Pathogenic
2
6
8
0
16
VUS
10
173
35
7
225
Likely Benign
0
0
3
99
102
Benign
0
0
0
0
0
Conflicting
15
Total17190127106455

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

B3GALT6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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