B3GALNT2

protein-coding

beta-1,3-N-acetylgalactosaminyltransferase 2, the group of Beta 3-glycosyltransferases

Gene summary

This gene encodes a member of the glycosyltransferase 31 family. The encoded protein synthesizes GalNAc:beta-1,3GlcNAc, a novel carbohydrate structure, on N- and O-glycans. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Mar 2013]

MANE transcript

NM_152490.5

Inheritance

ClinVar variants

P:67U:213B:124

Top phenotype

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 11

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr1:235,447,190-235,504,452

External References & Databases

Ensembl (ENSG00000162885)

Transcript & Mutation Effects

hg38 • Region Span ~57.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive non-syndromic intellectual disabilitySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019502

Submitter: Orphanet

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014071

Submitter: Labcorp Genetics (formerly Invitae)

intellectual disabilityLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0001071

Submitter: Ambry Genetics

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014071

Submitter: Ambry Genetics

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014071

Submitter: PanelApp Australia

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014071

Submitter: ClinGen

*B3GALNT2* was first reported in relation to autosomal recessive muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11 in 2013 (Stevens et al., PMID: 23453667). Eleven variants (nonsense, missense, frameshift) that have been reported in seven probands in three publications (PMIDs: 23453667, 24084573, 40665687) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is known to be loss of function. This gene-disease relationship is also supported by a knockout zebrafish model (PMID: 23453667), an enzyme activity assay (PMID: 40665687), and a glycosylation assay (PMID: 40665687). In summary, there is definitive evidence supporting the relationship between *B3GALNT2* and autosomal recessive muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11. 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 15 December 2025 (SOP Version 11).

muscle-eye-brain diseaseSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018939

Submitter: Orphanet

muscular dystrophy-dystroglycanopathy, type ASUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0000171

Submitter: Orphanet

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014071

Submitter: Genomics England PanelApp

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014071

Submitter: G2P

Clinical Genomic Database (CGD)

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 11AR

Manifestation: Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 23453667

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to B3GALNT2 variants in ClinVar

8 Conditions Cataloged

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11Total: 445

not providedTotal: 102

Inborn genetic diseasesTotal: 73

not specifiedTotal: 34

B3GALNT2-related disorderTotal: 17

B3GALNT2-related disordersTotal: 6

DystroglycanopathyTotal: 1

Muscular dystrophy-dystroglycanopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152490.5. 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			1 clinvar	115 clinvar		116
missense		7 clinvar	207 clinvar	8 clinvar	1 clinvar	223
nonsense	12 clinvar	6 clinvar	1 clinvar			19
start loss		1 clinvar				1
frameshift	20 clinvar	4 clinvar	4 clinvar			28
splice donor/acceptor (+/-2bp)	4 clinvar	13 clinvar				17
Total	36	31	213	123	1	404

Highest pathogenic variant AF is 0.00027634032

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152490.5	RefSeq	NP_689703.1	12	MANE Select
ENST00000366600.8	Ensembl	ENSP00000355559.3	12	MANE Select
NM_001277155.3	RefSeq	NP_001264084.1	8	Standard
ENST00000313984.3	Ensembl	ENSP00000315678.3	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
b3galnt2	Danio rerio	Structure: skeletal muscle cell Quality: disorganized abnormal

Gene / Model

Organism

Observed Phenotype

b3galnt2

Danio rerio

Structure: skeletal muscle cell

Quality: disorganized

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mannose type O-glycan biosynthesis - Homo sapiens (human)
Post-translational protein modification
Metabolism of proteins
O-linked glycosylation

Biological Process

protein glycosylation
protein O-linked glycosylation

Molecular Function

acetylglucosaminyltransferase activity
acetylgalactosaminyltransferase activity
galactosyltransferase activity

Cellular Component

Golgi membrane
endoplasmic reticulum
endoplasmic reticulum membrane
Golgi apparatus
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000366600
Coding exons: 12
Length: 54544
Individuals with no LoFs: 125635
Homozygous LoFs: 0
Heterozygous LoFs: 113
Defined: 125748
p: 0.000449

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.951	222	266	0.836	0.0000144	3252
Missense (PolyPhen)		53	62.714	0.84511		732
Synonymous	0.716	95	104	0.911	0.00000631	961
Loss of Function	2.20	15	27.4	0.547	0.00000147	309

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.00099	0.00099	rare
East Asian	0.00060	0.00060	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00066	0.00064	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Beta-1,3-N-acetylgalactosaminyltransferase that synthesizes a unique carbohydrate structure, GalNAc-beta-1- 3GlcNAc, on N- and O-glycans. Has no galactose nor galactosaminyl transferase activity toward any acceptor substrate. Involved in alpha-dystroglycan (DAG1) glycosylation: acts coordinately with GTDC2/POMGnT2 to synthesize a GalNAc-beta3-GlcNAc-beta-terminus at the 4-position of protein O-mannose in the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine- beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan, which is required for binding laminin G-like domain-containing extracellular proteins with high affinity. {ECO:0000269|PubMed:14724282, ECO:0000269|PubMed:23453667, ECO:0000269|PubMed:23929950}.;
Disease: DISEASE: Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A11 (MDDGA11) [MIM:615181]: An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, eye malformations, profound mental retardation, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease. {ECO:0000269|PubMed:23453667}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.850
RVIS EVS: -0.71
RVIS percentile EVS: 14.5

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.155

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium