B3GLCT

protein-coding

beta 3-glucosyltransferase, the group of Beta 3-glycosyltransferases

Gene summary

The protein encoded by this gene is a beta-1,3-glucosyltransferase that transfers glucose to O-linked fucosylglycans on thrombospondin type-1 repeats (TSRs) of several proteins. The encoded protein is a type II membrane protein. Defects in this gene are a cause of Peters-plus syndrome (PPS).[provided by RefSeq, Mar 2009]

Previous symbols:

B3GALTL

MANE transcript

NM_194318.4

Inheritance

ClinVar variants

P:22U:132B:56

Top phenotype

Peters-plus syndrome

gnomAD constraint

pLI —, LoF o/e 0.93

Max pathogenic AF

—

Genomic locus

chr13:31,199,975-31,332,276

External References & Databases

Ensembl (ENSG00000187676)

Transcript & Mutation Effects

hg38 • Region Span ~132.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Peters plus syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009856

Submitter: G2P

Peters plus syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009856

Submitter: Labcorp Genetics (formerly Invitae)

Peters plus syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009856

Submitter: ClinGen

*B3GLCT* was first reported in relation to autosomal recessive Peters plus syndrome in 2006 (Lesnik Oberstein et al. PMID:16909395). Twelve variants (missense, nonsense, frameshift, splicing) that have been reported in 7 probands in 2 publications (PMIDs: 16909395, 23889335) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts) has been reached. Peters plus syndrome is characterized by ocular features, systemic malformations, developmental delay, growth retardation, short stature, and brachydactyly. The disease mechanism appears to be biallelic loss of function. Heterozygous carriers are reportedly unaffected. This gene-disease relationship is also supported by the biochemical function of B3GLCT, which is involved in the synthesis of Glcβ1,3Fucα1-O-linked disaccharide found on the thrombospondin type-1 repeats (TSRs) of many biologically important proteins (PMID: 17032646). Additional experimental evidence includes in vitro and in vivo assays showing a defect in glycosylation (PMIDs 34058199, 18199743) as well as animal models (PMIDs 31600785, 28926587). In summary, there is definitive evidence supporting the relationship between *B3GLCT *and autosomal recessive Peters plus syndrome.This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on the meeting date January 5, 2026 (SOP Version 11).

Peters plus syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009856

Submitter: PanelApp Australia

Peters plus syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009856

Submitter: Orphanet

Peters plus syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009856

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Peters-plus syndromeAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: Ophthalmologic

Rationale: Individuals may be at high risk for ophthalmologic complications, including glaucoma, and surveillance may allow early interventions and management

Refs: 16909395; 18199743; 18798333; 19796186; 20301637; 21067481; 21671750; 22759511

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to B3GLCT variants in ClinVar

8 Conditions Cataloged

Peters plus syndromeTotal: 161

Inborn genetic diseasesTotal: 86

not providedTotal: 54

not specifiedTotal: 22

B3GLCT-related disorderTotal: 17

B3GLCT-related disordersTotal: 2

Marfanoid habitus and intellectual disabilityTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_194318.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			8 clinvar	47 clinvar	1 clinvar	56
missense	1 clinvar	3 clinvar	115 clinvar	7 clinvar	1 clinvar	127
nonsense	2 clinvar	1 clinvar	3 clinvar			6
start loss						0
frameshift	5 clinvar	3 clinvar	1 clinvar			9
splice donor/acceptor (+/-2bp)	2 clinvar	5 clinvar	5 clinvar			12
Total	10	12	132	54	2	210

Highest pathogenic variant AF is 0.001034188

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_194318.4	RefSeq	NP_919299.3	15	MANE Select
ENST00000343307.5	Ensembl	ENSP00000343002.4	15	MANE Select
ENST00000873566.1	Ensembl	ENSP00000543625.1	13	Standard
ENST00000873566.2	Ensembl	ENSP00000543625.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Other types of O-glycan biosynthesis - Homo sapiens (human)
Post-translational protein modification
Metabolism of proteins
O-glycosylation of TSR domain-containing proteins
O-linked glycosylation

Biological Process

fucose metabolic process
protein O-linked fucosylation

Molecular Function

acetylglucosaminyltransferase activity
transferase activity, transferring glycosyl groups

Cellular Component

endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000343307
Coding exons: 15
Length: 132341
Individuals with no LoFs: 125450
Homozygous LoFs: 1
Heterozygous LoFs: 297
Defined: 125748
p: 0.00119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.392	237	255	0.931	0.0000129	3264
Missense (PolyPhen)		83	94.793	0.87559		1187
Synonymous	-1.55	116	96.6	1.20	0.00000591	908
Loss of Function	0.347	26	28.0	0.929	0.00000125	359

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00068	0.00068	rare
Latino/Admixed American	0.00084	0.00084	rare
Ashkenazi Jewish	0.00070	0.00069	rare
East Asian	0.00027	0.00027	rare
Finnish	0.0041	0.0037	notable
European (Non-Finnish)	0.0013	0.0013	notable
South Asian	0.00043	0.00042	rare
Other	0.00099	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: O-glucosyltransferase that transfers glucose toward fucose with a beta-1,3 linkage. Specifically glucosylates O-linked fucosylglycan on TSP type-1 domains of proteins, thereby contributing to elongation of O-fucosylglycan. {ECO:0000269|PubMed:16899492}.;

Recessive Scores

pRec: 0.138

Intolerance Scores

RVIS EVS: 0.07
RVIS percentile EVS: 58.96

Essentials

Essential (gene trap): N