GeneBe

B4GALT7

protein-coding

beta-1,4-galactosyltransferase 7, the group of Beta 4-glycosyltransferases

Gene summary

This gene is a member of the beta-1,4-galactosyltransferase (beta4GalT) family. Family members encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose. Each beta4GalT member has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus which then remains uncleaved to function as a transmembrane anchor. The enzyme encoded by this gene attaches the first galactose in the common carbohydrate-protein linkage (GlcA-beta1,3-Gal-beta1,3-Gal-beta1,4-Xyl-beta1-O-Ser) found in proteoglycans. This enzyme differs from other beta4GalTs because it lacks the conserved Cys residues found in beta4GalT1-beta4GalT6 and it is located in cis-Golgi instead of trans-Golgi. Mutations in this gene have been associated with the progeroid form of Ehlers-Danlos syndrome. [provided by RefSeq, Oct 2009]

MANE transcript

NM_007255.3

Inheritance

AR

ClinVar variants

P:30U:200B:127

Top phenotype

Ehlers-Danlos syndrome, spondylodysplastic type, 1

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr5:177,600,132-177,610,330

External References & Databases

Ensembl (ENSG00000027847)NCBI Gene (11285)OMIM (604327)HGNC:930GenCCUniProt (Q9UBV7)AlphaFoldClinVar (B4GALT7)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~10.2 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Ehlers-Danlos syndrome, spondylodysplastic type, 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020682

Submitter: Genomics England PanelApp

Ehlers-Danlos syndrome, spondylodysplastic typeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0007526

Submitter: Orphanet

Ehlers-Danlos syndrome, spondylodysplastic type, 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0020682

Submitter: G2P

Ehlers-Danlos syndrome, spondylodysplastic type, 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020682

Submitter: Labcorp Genetics (formerly Invitae)

Ehlers-Danlos syndrome, spondylodysplastic type, 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020682

Submitter: PanelApp Australia

Ehlers-Danlos syndrome, spondylodysplastic type, 1MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0020682

Submitter: Ambry Genetics

Ehlers-Danlos syndrome, spondylodysplastic type, 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0020682

Submitter: ClinGen

B4GALT7 was first reported in relation to autosomal recessive Ehlers-Danlos Syndrome, Spondylodysplastic Type in 1999 (Almeida et al., PMID: 10473568; and Okajima et al., PMID: 10506123). Prenatal features of this condition may include increased nuchal translucency, edema, cystic hygroma, absent digits on hands, and pulmonary hypoplasia. Features have manifested as early as 10 weeks gestation (PMIDs: 26940150, 27320698, 31278392). Additionally, B4GALT7 is associated with perinatal lethality, including spontaneous abortion, in some cases, as well as low birth weight and preterm birth. 12 variants (missense, nonsense, frameshift) that have been reported in at least 14 probands in 9 publications (PMIDs: 10506123, 23956117, 26940150, 27320698, 28882145, 30914273, 31278392, 31614862, 34193099) are included in this curation. The mechanism of pathogenicity appears to be loss-of-function. This gene-disease relationship is also supported by experimental evidence (zebrafish and horse models; PMIDs: 27793082, 31862401). In the horse model, the mutants exhibited short stature, pectus excavatum, and hypermobility. In the zebrafish model, the mutants showed reduced body and head length, as well as craniofacial and morphological anomalies. Both of these phenotypes overlap with the human phenotype. In summary, there is definitive evidence supporting the relationship between B4GALT7 and autosomal recessive Ehlers-Danlos Syndrome, Spondylodysplastic Type. 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 Skeletal Disorders GCEP on the meeting date 8/5/2024 (SOP Version 10).

Clinical Genomic Database (CGD)

Ehlers-Danlos syndrome, spondylodysplastic type, 1AR

Manifestation: Craniofacial; Dermatologic; Musculoskeletal; Neurologic

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: 3631078; 10473568; 10506123; 15211654; 16583246; 20809901; 24755949Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to B4GALT7 variants in ClinVar

11 Conditions Cataloged
Spondylodysplastic Ehlers-Danlos syndromeTotal: 316
not providedTotal: 116
not specifiedTotal: 89
Inborn genetic diseasesTotal: 78
Ehlers-Danlos syndrome, spondylodysplastic type, 1Total: 20
B4GALT7-related disorderTotal: 17
Ehlers-Danlos syndromeTotal: 13
Fetal anomalies with a likely genetic causeTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007255.3. 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
4
clinvar
117
clinvar
1
clinvar
 122
missense
3
clinvar
4
clinvar
188
clinvar
9
clinvar
 204
nonsense
3
clinvar
2
clinvar
2
clinvar
 7
start loss
0
frameshift
12
clinvar
2
clinvar
5
clinvar
 19
splice donor/acceptor (+/-2bp)
4
clinvar
1
clinvar
 5
Total18122001261357

Highest pathogenic variant AF is 0.0006179604

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_007255.3RefSeqNP_009186.16MANE Select
ENST00000029410.10EnsemblENSP00000029410.56MANE Select
ENST00000505433.5EnsemblENSP00000425591.13Standard
ENST00000505468.1EnsemblENSP00000420886.12Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
b4galt7Danio rerio

Structure: cranial cartilage

Quality: morphology

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

  • carbohydrate metabolic process
  • glycosaminoglycan biosynthetic process
  • proteoglycan metabolic process
  • cellular protein modification process
  • protein N-linked glycosylation

Molecular Function

  • beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase activity
  • protein binding
  • galactosyltransferase activity
  • manganese ion binding
  • xylosylprotein 4-beta-galactosyltransferase activity

Cellular Component

  • Golgi membrane
  • Golgi apparatus
  • integral component of membrane
  • Golgi cisterna membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000029410
Coding exons
6
Length
10248
Individuals with no LoFs
125665
Homozygous LoFs
0
Heterozygous LoFs
83
Defined
125748
p
0.000330
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.3112272141.060.00001422112
Missense (PolyPhen)9994.5111.0475912
Synonymous-0.5839790.01.080.00000603667
Loss of Function1.28813.00.6155.60e-7145

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000630.00062rare
Latino/Admixed American0.000120.00012rare
Ashkenazi Jewish00.0absent
East Asian0.000980.00098rare
Finnish0.000460.00046rare
European (Non-Finnish)0.000240.00022rare
South Asian0.000520.00052rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Required for the biosynthesis of the tetrasaccharide linkage region of proteoglycans, especially for small proteoglycans in skin fibroblasts. {ECO:0000269|PubMed:24052259}.;

Recessive Scores

pRec
0.118

Intolerance Scores

LoFtool
0.413
RVIS EVS
-0.73
RVIS percentile EVS
14.02

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.108

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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