Congenital disorder of glycosylation, type iit

Summary

Congenital disorder of glycosylation, type iit (MONDO:0030043) is a disease caused by GALNT2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: GALNT2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 16

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital disorder of glycosylation, type iit
Mondo ID	MONDO:0030043
OMIM	618885
DOID	DOID:0051049
UMLS	C5394387
MedGen	1709627
GARD	0025515
Is cancer (heuristic)	no

Also known as: Cdg Iit · CDG2T · CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIt

Data availability: 16 ClinVar variants · 2 GenCC gene-disease records.

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 › congenital disorder of glycosylation type II › congenital disorder of glycosylation, type iit

Related subtypes (25): MGAT2-congenital disorder of glycosylation, leukocyte adhesion deficiency type II, SLC35A2-congenital disorder of glycosylation, SLC35A1-congenital disorder of glycosylation, MOGS-congenital disorder of glycosylation, B4GALT1-congenital disorder of glycosylation, COG7-congenital disorder of glycosylation, COG8-congenital disorder of glycosylation, COG1-congenital disorder of glycosylation, COG4-congenital disorder of glycosylation, COG5-congenital disorder of glycosylation, COG6-congenital disorder of glycosylation, TMEM165-congenital disorder of glycosylation, SLC39A8-CDG, CCDC115-CDG, TMEM199-CDG, congenital disorder of glycosylation, type IIr, congenital disorder of glycosylation, type 2v, congenital disorder of glycosylation, type IIw, congenital disorder of glycosylation, type IIq, congenital disorder of glycosylation, type IIy, congenital disorder of glycosylation, type IIz, congenital disorder of glycosylation, type IIaa, congenital disorder of glycosylation, type IIbb, congenital disorder of glycosylation, type IIcc

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

ClinVar germline variants

16 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 4 likely pathogenic, 4 pathogenic, 1 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
4689509	NC_000001.10:g.(?230202984)(230417869_?)del	GALNT2	Pathogenic	criteria provided, single submitter
873545	NM_004481.5(GALNT2):c.865C>T (p.Gln289Ter)	GALNT2	Pathogenic	criteria provided, single submitter
873546	NM_004481.5(GALNT2):c.598C>T (p.Arg200Ter)	GALNT2	Pathogenic	criteria provided, multiple submitters, no conflicts
873547	NM_004481.5(GALNT2):c.296dup (p.Tyr99Ter)	GALNT2	Pathogenic	no assertion criteria provided
1065626	NM_004481.5(GALNT2):c.623G>A (p.Arg208Gln)	GALNT2	Likely pathogenic	criteria provided, single submitter
4813785	NM_004481.5(GALNT2):c.691G>T (p.Glu231Ter)	GALNT2	Likely pathogenic	criteria provided, single submitter
873544	NM_004481.5(GALNT2):c.311T>C (p.Phe104Ser)	GALNT2	Likely pathogenic	criteria provided, single submitter
873548	NM_004481.5(GALNT2):c.629G>C (p.Arg210Pro)	GALNT2	Likely pathogenic	criteria provided, single submitter
1101345	NM_004481.5(GALNT2):c.648A>T (p.Gln216His)	GALNT2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1339903	NM_004481.5(GALNT2):c.526G>C (p.Asp176His)	GALNT2	Uncertain significance	criteria provided, single submitter
1709527	NM_004481.5(GALNT2):c.449C>T (p.Ser150Leu)	GALNT2	Uncertain significance	criteria provided, single submitter
1709528	NM_004481.5(GALNT2):c.460A>T (p.Arg154Trp)	GALNT2	Uncertain significance	criteria provided, single submitter
2442077	NM_004481.5(GALNT2):c.1372G>A (p.Asp458Asn)	GALNT2	Uncertain significance	criteria provided, single submitter
4077147	NM_004481.5(GALNT2):c.541C>T (p.Pro181Ser)	GALNT2	Uncertain significance	criteria provided, single submitter
4529502	NM_004481.5(GALNT2):c.1616G>C (p.Cys539Ser)	GALNT2	Uncertain significance	criteria provided, single submitter
785954	NM_004481.5(GALNT2):c.1077C>T (p.His359=)	GALNT2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
GALNT2	Strong	Autosomal recessive	congenital disorder of glycosylation, type iit	3

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
GALNT2	HGNC:4124	ENSG00000143641	Q10471	Polypeptide N-acetylgalactosaminyltransferase 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GALNT2	Polypeptide N-acetylgalactosaminyltransferase 2	Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor.

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)
GALNT2	Enzyme (other)	yes	2.4.1.41	Ricin_B_lectin, Glyco_trans_2-like, 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
ascending aorta	1
descending thoracic aorta	1
thoracic aorta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GALNT2	285	ubiquitous	marker	descending thoracic aorta, thoracic aorta, ascending aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GALNT2	1,461

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GALNT2	Q10471	13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
COPI-independent Golgi-to-ER retrograde traffic	1	207.6×	0.005	GALNT2
O-linked glycosylation of mucins	1	184.2×	0.005	GALNT2

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
positive regulation of immunoglobulin production	1	481.5×	0.005	GALNT2
protein O-linked glycosylation via N-acetylgalactosamine	1	432.1×	0.005	GALNT2
protein O-linked glycosylation	1	224.7×	0.006	GALNT2
protein maturation	1	163.6×	0.006	GALNT2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GALNT2	2	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GALLIC ACID	2	GALNT2
ELLAGIC ACID	2	GALNT2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GALNT2	19	Binding:19

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GALNT2	2.4.1.41	polypeptide N-acetylgalactosaminyltransferase

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

2 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.

Compound	Max phase	Cohort target (bioactivity)
GALLIC ACID	2	GALNT2
ELLAGIC ACID	2	GALNT2

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	1	GALNT2
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.