B3GALT6

Chr 1AR

beta-1,3-galactosyltransferase 6

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

NCBI Gene: 126792 ENSG00000176022 UniProt: Q96L58 OMIM: 615291

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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. [provided by RefSeq, Jun 2013]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Al-Gazali syndromeMIM #609465

Ehlers-Danlos syndrome, spondylodysplastic type, 2MIM #615349

Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fracturesMIM #271640

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · B3GALT6-congenital disorder of glycosylation · AR · ClinGen 2025

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.43

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — B3GALT6

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.43LOEUF

pLI 0.023

Z-score 0.93

OE 0.56 (0.26–1.43)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.26Z-score

OE missense 0.69 (0.59–0.82)

93 obs / 134.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.26–1.43)

0≤0.351.4

Missense OE?0.69 (0.59–0.82)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 3 / 5.3Missense obs/exp: 93 / 134.1Syn Z: 0.41

Background carrier burden — how many people carry a rare variant somewhere in B3GALT6?

gnomAD v4 · ~710k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 84

618 rare PASS variants

Rare truncating (LoF)

1 in 1,200

85 rare PASS variants

Rare synonymous (reference)

1 in 160

341 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for B3GALT6. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~550k	1 in 120	1 in 1,400
South Asian	~41k	1 in 87	1 in 570
Remaining (unassigned)	~29k	1 in 58	1 in 1,400
African / African American	~21k	1 in 92	1 in 1,000
Admixed American	~21k	1 in 87	1 in 460
European (Finnish)	~21k	1 in 300	1 in 1,400
East Asian	~19k	1 in 130	1 in 1,800
Ashkenazi Jewish	~13k	1 in 1,200	≈ 1 in 3,600
Middle Eastern	~2,809	1 in 95	1 in 300

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.