GeneBe

B3GAT3

protein-coding

beta-1,3-glucuronyltransferase 3, the group of Beta-1,3-glucuronyltransferases

Gene summary

The protein encoded by this gene is a member of the glucuronyltransferase gene family, enzymes that exhibit strict acceptor specificity, recognizing nonreducing terminal sugars and their anomeric linkages. This gene product catalyzes the formation of the glycosaminoglycan-protein linkage by way of a glucuronyl transfer reaction in the final step of the biosynthesis of the linkage region of proteoglycans. A pseudogene of this gene has been identified on chromosome 3. [provided by RefSeq, Dec 2013]

MANE transcript

NM_012200.4

Inheritance

AD, AR

ClinVar variants

P:37U:135B:81

Top phenotype

Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects

gnomAD constraint

pLI —, LoF o/e 0.84

Max pathogenic AF

—

Genomic locus

chr11:62,615,296-62,622,154

External References & Databases

Ensembl (ENSG00000149541)NCBI Gene (26229)OMIM (606374)HGNC:923GenCCUniProt (O94766)AlphaFoldClinVar (B3GAT3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~6.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

Larsen-like syndrome, B3GAT3 typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009511

Submitter: PanelApp Australia

Larsen-like syndrome, B3GAT3 typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009511

Submitter: G2P

Larsen-like syndrome, B3GAT3 typeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009511

Submitter: Orphanet

Larsen-like syndrome, B3GAT3 typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009511

Submitter: Labcorp Genetics (formerly Invitae)

Larsen-like syndrome, B3GAT3 typeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0009511

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defectsAR

Manifestation: Cardiovascular; Craniofacial; Musculoskeletal

Intervention: General

Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management

Refs: 21763480; 24668659Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to B3GAT3 variants in ClinVar

9 Conditions Cataloged
Larsen-like syndrome, B3GAT3 typeTotal: 244
not providedTotal: 81
Inborn genetic diseasesTotal: 55
not specifiedTotal: 24
B3GAT3-related disorderTotal: 7
MULTIPLE JOINT DISLOCATIONS, SHORT STATURE, AND CRANIOFACIAL DYSMORPHISM WITHOUT CONGENITAL HEART DEFECTSTotal: 3
B3GAT3-related disordersTotal: 3
MULTIPLE JOINT DISLOCATIONS, SHORT STATURE, AND CRANIOFACIAL DYSMORPHISM WITH CONGENITAL HEART DEFECTSTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012200.4. 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
75
clinvar
 78
missense
6
clinvar
5
clinvar
128
clinvar
5
clinvar
1
clinvar
 145
nonsense
3
clinvar
7
clinvar
2
clinvar
 12
start loss
4
clinvar
 4
frameshift
6
clinvar
3
clinvar
1
clinvar
 10
splice donor/acceptor (+/-2bp)
3
clinvar
1
clinvar
 4
Total1522135801253

Highest pathogenic variant AF is 0.000075651405

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_012200.4RefSeqNP_036332.25MANE Select
ENST00000265471.10EnsemblENSP00000265471.55MANE Select
NM_001288721.2RefSeqNP_001275650.15Standard
NM_001288722.2RefSeqNP_001275651.15Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
b3gat3Danio rerio

Structure: pharyngeal arch 3-7

Quality: shape

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate - Homo sapiens (human)
  • Glycosaminoglycan biosynthesis - heparan sulfate / heparin - Homo sapiens (human)
  • Metabolism of carbohydrates
  • A tetrasaccharide linker sequence is required for GAG synthesis
  • Heparan sulfate/heparin (HS-GAG) metabolism

Biological Process

  • glycosaminoglycan biosynthetic process
  • protein glycosylation
  • heparan sulfate proteoglycan biosynthetic process
  • glycosaminoglycan metabolic process
  • positive regulation of catalytic activity

Molecular Function

  • protein binding
  • galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase activity
  • glucuronosyltransferase activity
  • metal ion binding
  • protein phosphatase activator activity

Cellular Component

  • Golgi membrane
  • Golgi apparatus
  • cis-Golgi network
  • membrane
  • integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000265471
Coding exons
5
Length
6880
Individuals with no LoFs
125715
Homozygous LoFs
0
Heterozygous LoFs
30
Defined
125745
p
0.000119
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.6921782060.8640.00001362087
Missense (PolyPhen)4754.9750.85493604
Synonymous-0.2269390.31.030.00000514768
Loss of Function0.5921315.50.8389.39e-7139

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.000120.00012rare
Ashkenazi Jewish0.000100.000099rare
East Asian00.0absent
Finnish0.0000460.000046rare
European (Non-Finnish)0.000150.00015rare
South Asian0.000160.00016rare
Other0.000330.00033rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Glycosaminoglycans biosynthesis (PubMed:25893793). Involved in forming the linkage tetrasaccharide present in heparan sulfate and chondroitin sulfate. Transfers a glucuronic acid moiety from the uridine diphosphate-glucuronic acid (UDP-GlcUA) to the common linkage region trisaccharide Gal-beta-1,3-Gal-beta-1,4- Xyl covalently bound to a Ser residue at the glycosaminylglycan attachment site of proteoglycans. Can also play a role in the biosynthesis of l2/HNK-1 carbohydrate epitope on glycoproteins. Shows strict specificity for Gal-beta-1,3-Gal-beta-1,4-Xyl, exhibiting negligible incorporation into other galactoside substrates including Galbeta1-3Gal beta1-O-benzyl, Galbeta1- 4GlcNAc and Galbeta1-4Glc. Stimulates 2-phosphoxylose phosphatase activity of PXYLP1 in presence of uridine diphosphate-glucuronic acid (UDP-GlcUA) during completion of linkage region formation (PubMed:24425863). {ECO:0000269|PubMed:24425863, ECO:0000269|PubMed:25893793}.;
Disease
DISEASE: Multiple joint dislocations, short stature, and craniofacial dysmorphism with or without congenital heart defects (JDSCD) [MIM:245600]: An autosomal recessive disease characterized by dysmorphic facies, bilateral dislocations of the elbows, hips, and knees, clubfeet, and short stature, as well as cardiovascular defects. {ECO:0000269|PubMed:21763480, ECO:0000269|PubMed:24668659, ECO:0000269|PubMed:25893793, ECO:0000269|PubMed:26086840}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.131

Intolerance Scores

LoFtool
0.600
RVIS EVS
-0.2
RVIS percentile EVS
38.82

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.434

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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