A4GALT-congenital disorder of glycosylation

Summary

A4GALT-congenital disorder of glycosylation (MONDO:0100587) is a disease caused by A4GALT (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: A4GALT (GenCC Definitive)
• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	A4GALT-congenital disorder of glycosylation
Mondo ID	MONDO:0100587
GARD	0027281
Is cancer (heuristic)	no

Also known as: A4GALT-CDG · A4GALT-congenital disorder of glycosylation · A4GALT-related congenital disorder of glycosylation

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › congenital disorder of glycosylation › A4GALT-congenital disorder of glycosylation

Related subtypes (24): congenital disorder of glycosylation type I, congenital disorder of glycosylation type II, Larsen-like syndrome, B3GAT3 type, Ehlers-Danlos syndrome, musculocontractural type, temtamy preaxial brachydactyly syndrome, progressive myoclonic epilepsy type 3, autosomal recessive limb-girdle muscular dystrophy type 2P, seizures-scoliosis-macrocephaly syndrome, disorder of protein N-glycosylation, disorder of protein O-glycosylation, inborn disorder of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation, disorder of multiple glycosylation, XYLT1-congenital disorder of glycosylation, congenital muscular dystrophy with intellectual disability, congenital disorder of glycosylation syndrome type 4, congenital disorder of glycosylation with defective fucosylation, SLC10A7-congenital disorder of glycosylation, ALG14-congenital disorder of glycosylation, B3GALT6-congenital disorder of glycosylation, FAM20B-congenital disorder of glycosylation, ALG10-congenital disorder of glycosylation, congenital disorder of glycosylation, type Ibb, congenital disorder of glycosylation, type Iw, autosomal dominant, congenital disorder of glycosylation, type 1DD

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
A4GALT	Definitive	Autosomal recessive	A4GALT-congenital disorder of glycosylation

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
A4GALT	HGNC:18149	ENSG00000128274	Q9NPC4	Lactosylceramide 4-alpha-galactosyltransferase	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
A4GALT	Lactosylceramide 4-alpha-galactosyltransferase	Glycosyltransferase involved in biosynthesis of P1, P(k) and the rare NOR antigens of P1PK histo-blood group system.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
A4GALT	Enzyme (other)	yes	2.4.1.228	GlycoTrfase_DXD_sugar-bd_CS, A1-4-GlycosylTfrase_dom, Nucleotide-diphossugar_trans

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
olfactory segment of nasal mucosa	1
right atrium auricular region	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
A4GALT	186	ubiquitous	marker	apex of heart, olfactory segment of nasal mucosa, right atrium auricular region

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
A4GALT	814

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
A4GALT	Q9NPC4	89.54

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Glycosphingolipid biosynthesis	1	601.0×	0.008	A4GALT
Glycosphingolipid metabolism	1	300.5×	0.008	A4GALT
Sphingolipid metabolism	1	167.9×	0.010	A4GALT
Metabolism of lipids	1	31.6×	0.040	A4GALT
Metabolism	1	11.6×	0.086	A4GALT

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
globoside biosynthetic process	1	5617.3×	5e-04	A4GALT
plasma membrane organization	1	887.0×	0.002	A4GALT
glycosphingolipid biosynthetic process	1	601.9×	0.002	A4GALT

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
A4GALT	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
A4GALT	2.4.1.228	lactosylceramide 4-alpha-galactosyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	A4GALT
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
A4GALT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.