GALNT2

Summary

GALNT2 (polypeptide N-acetylgalactosaminyltransferase 2, HGNC:4124) is a protein-coding gene on chromosome 1q42.13, encoding Polypeptide N-acetylgalactosaminyltransferase 2 (Q10471). 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.

This gene encodes a member of the glycosyltransferase 2 protein family. Members of this family initiate mucin-type O-glycoslation of peptides in the Golgi apparatus. The encoded protein may be involved in O-linked glycosylation of the immunoglobulin A1 hinge region. This gene may influence triglyceride levels, and may be involved Type 2 diabetes, as well as several types of cancer. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2590 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital disorder of glycosylation, type iit (Strong, ClinGen) — +1 more curated relationship
• GWAS associations: 123
• Clinical variants (ClinVar): 229 total — 4 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 44
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004481

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4124
Approved symbol	GALNT2
Name	polypeptide N-acetylgalactosaminyltransferase 2
Location	1q42.13
Locus type	gene with protein product
Status	Approved
Aliases	GalNAc-T2
Ensembl gene	ENSG00000143641
Ensembl biotype	protein_coding
OMIM	602274
Entrez	2590

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000366672, ENST00000485438, ENST00000488903, ENST00000492568, ENST00000494106, ENST00000868579, ENST00000868580, ENST00000868581, ENST00000935979, ENST00000935980, ENST00000935981, ENST00000935982, ENST00000950855, ENST00000950856, ENST00000950857

RefSeq mRNA: 2 — MANE Select: NM_004481 NM_001291866, NM_004481

CCDS: CCDS1582

Canonical transcript exons

ENST00000366672 — 16 exons

Exon	Start	End
ENSE00001007560	230249184	230249271
ENSE00001007561	230246063	230246150
ENSE00001007564	230250457	230250560
ENSE00001442291	230067238	230067406
ENSE00001935591	230279303	230282122
ENSE00003477846	230265241	230265367
ENSE00003492256	230236353	230236420
ENSE00003503459	230255218	230255344
ENSE00003522264	230203137	230203290
ENSE00003533449	230262573	230262665
ENSE00003542410	230274445	230274564
ENSE00003551620	230262922	230263005
ENSE00003574562	230236014	230236112
ENSE00003621838	230236660	230236725
ENSE00003631244	230243306	230243427
ENSE00003662413	230178218	230178311

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 96.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 82.4244 / max 598.8129, expressed in 1827 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9018	74.8964	1826
9019	6.1509	1655
9017	1.3514	915
9016	0.0257	9

Top tissues by expression

292 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
descending thoracic aorta	UBERON:0002345	96.87	gold quality
thoracic aorta	UBERON:0001515	96.75	gold quality
ascending aorta	UBERON:0001496	96.72	gold quality
cartilage tissue	UBERON:0002418	96.56	gold quality
mucosa of stomach	UBERON:0001199	96.30	gold quality
right coronary artery	UBERON:0001625	96.20	gold quality
adrenal tissue	UBERON:0018303	96.07	gold quality
stromal cell of endometrium	CL:0002255	96.05	gold quality
body of pancreas	UBERON:0001150	95.62	gold quality
palpebral conjunctiva	UBERON:0001812	95.47	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.22	gold quality
lower esophagus	UBERON:0013473	95.17	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.12	gold quality
right lobe of liver	UBERON:0001114	94.87	gold quality
left coronary artery	UBERON:0001626	94.82	gold quality
coronary artery	UBERON:0001621	94.80	gold quality
left adrenal gland	UBERON:0001234	94.50	gold quality
decidua	UBERON:0002450	94.37	silver quality
left adrenal gland cortex	UBERON:0035825	94.34	gold quality
saphenous vein	UBERON:0007318	94.26	gold quality
urethra	UBERON:0000057	94.18	gold quality
gastrocnemius	UBERON:0001388	94.18	gold quality
aorta	UBERON:0000947	94.17	gold quality
liver	UBERON:0002107	94.17	gold quality
right adrenal gland	UBERON:0001233	94.15	gold quality
adrenal cortex	UBERON:0001235	94.13	gold quality
adrenal gland	UBERON:0002369	94.03	gold quality
pancreas	UBERON:0001264	93.79	gold quality
muscle of leg	UBERON:0001383	93.68	gold quality
right adrenal gland cortex	UBERON:0035827	93.36	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

146 targeting GALNT2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3662	99.99	73.82	5684
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-551B-5P	99.96	71.28	3493

Literature-anchored findings (GeneRIF, showing 40)

• GalNAc T10 has a large and pronounced glycopeptide preference for Ser/Thr-O-GalNAc only at the +1 position from the acceptor site, whereas T1 and T2 have significantly reduced and variable preferences for Ser/Thr-O-GalNAc. (PMID:19460755)
• Data show that SNPs associated with TG in normolipidemic samples, including APOA5, TRIB1, TBL2, GCKR, GALNT2 and ANGPTL3 were significantly associated with HLP types 2B, 3, 4 and 5. (PMID:19656773)
• these findings clearly indicate that biological activity (catalytic capacity and glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation. (PMID:21651894)
• genetic association studies in rural populations in Guangxi, China: SNPs in GALNT2 (rs2144300; rs4846914) are associated with plasma lipid/lipoprotein levels in the general population; ethnic differences exist in Mulao and Han populations. (PMID:21933382)
• The status of the O-glycans attached to the EGFR was altered by GALNT2, changing EGFR responses after EGF binding. (PMID:21990321)
• Heterozygosity for a loss-of-function mutation in GALNT2 improves plasma triglyceride clearance in man. (PMID:22152306)
• Studies indicate that three loci for lipid levels identified by GWAS has identified functional genes GALNT2, TRIB1, and SORT1, and a functional variant at SORT1. (PMID:22418572)
• analysis of LIPG, CETP, and GALNT2 mutations in Caucasian families with extremely high HDL cholesterol (PMID:22952570)
• ppGalNAc-T2 may exert anti-proliferative and anti-metastatic activity through the decrease of MMP-2 and TGF-beta1. (PMID:22992780)
• Data suggest that GALNT2 and protein O-glycosylation are critical in extravillous trophoblast (EVT) invasion/placentation. GALNT2 is expressed in subpopulations of EVT in decidua; GALNT2 expression in EVT increases as pregnancy progresses. (PMID:23117232)
• GALNT2 is down-regulated in patients with type 2 diabetes (PMID:23894607)
• Endoplasmic reticulum localization of GalNAc-T2 Is Sufficient to Drive High Tn Expression. (PMID:23912186)
• findings suggest that GALNT2 plays an important role in the invasive behavior of OSCC and that targeting GALNT2 could be a promising approach for OSCC therapy (PMID:24582885)
• genome-wide association study in population in Finland: Data suggest that one SNP in GALNT2 (rs6684432) and two SNPs in VDBP (vitamin D binding protein; rs7041, rs705117) are associated with serum levels of VDBP in the male population studied. (PMID:24740207)
• promoter DNA hypermethylation of the ABCG1 and GALNT2 genes, but not the HMGCR gene, is associated with an increased risk of CHD. (PMID:25084356)
• Our findings suggest that GALNT2 regulates malignant phenotypes of neuroblastoma cells (PMID:25362349)
• Downregulation of GALNT2 is associated with IgA nephropathy. (PMID:25744272)
• Our data suggest a role of GALNT2 expression changes on serum triglycerides. (PMID:26239958)
• The present work indicates that SNP rs4846914 in GALNT2 gene is related to an increased risk of hypertension in China Han population, but the APOE gene is not. (PMID:26405973)
• Possible inter-locus interactions among the DOCK7, PCSK9 and GALNT2 SNPs were also noted. (PMID:26493351)
• Multiple hepatic regulatory variants at the GALNT2 GWAS locus have been found associated with high-density lipoprotein cholesterol. (PMID:26637976)
• Differences in lipid profiles between the Jing and Han populations might partially attribute to the DOCK7, PCSK9 and GALNT2 gene polymorphisms and their haplotypes determining different risk for the development of cardiovascular diseases. (PMID:26744084)
• The results suggest that rs4846913 and rs2144300 drive the association to HDL-C plasma levels through an inhibitory regulation of GALNT2. (PMID:26817450)
• Our results indicate that GALNT2 suppresses the malignant potential of gastric adenocarcinoma cells (PMID:26848976)
• The crystal structure of GalNAc-T2 with the galactose derivative traps the enzyme in an inactive form; this suggests that compounds only containing the beta-phosphate could be efficient ligands for the enzyme. Computational studies with GalNAc-T2 corroborate these findings and provide further insights into the mechanism of the catalytic cycle of this family of enzymes. (PMID:27071848)
• These results posit GALNT2 as a direct modulator of high density lipoprotein metabolism across mammals. (PMID:27508872)
• The presence of lectin domain T3lec or T4lec during ppGalNAc-T2 and ppGalNAc-T3 catalytic reaction had a clear inhibitory effect on GalNAc-T activity. (PMID:27738109)
• This study demonstrates that the polypeptide GalNAc-transferase 2 (GalNAc-T2) specifically O-glycosylates beta 1-adrenergic receptor at five residues in the extracellular N terminus, including the Ser-49 residue at the location of the common S49G single-nucleotide polymorphism. (PMID:28167537)
• GALNT2 rs12040273 variants might not be associated with the susceptibility of coronary artery disease or its severity in a Chinese Han population. The CC genotype could be associated with elevated serum HDL-C levels. (PMID:29351739)
• facilitates the malignant characteristics of glioma by influencing the O-glycosylation and phosphorylation of EGFR and the subsequent downstream PI3K/Akt/mTOR axis (PMID:31076460)
• we report the clinical, biochemical, and molecular features of seven patients from four families with GALNT2-congenital disorder of glycosylation (GALNT2-CDG), an O-linked glycosylation disorder (PMID:32293671)
• TLR7 in B cells promotes renal inflammation and Gd-IgA1 synthesis in IgA nephropathy. (PMID:32699192)
• GALNT2 Gene Variant rs4846914 Is Associated with Insulin and Insulin Resistance Depending on BMI in PCOS Patients: a Case-Control Study. (PMID:33171515)
• GALNT2 promotes cell proliferation, migration, and invasion by activating the Notch/Hes1-PTEN-PI3K/Akt signaling pathway in lung adenocarcinoma. (PMID:33785338)
• GALNT2/14 overexpression correlate with prognosis and methylation: potential therapeutic targets for lung adenocarcinoma. (PMID:33964375)
• Maternal GALNT2 Variations Affect Blood Pressure, Atherogenic Index, and Fetal Growth, Depending on BMI in Gestational Diabetes Mellitus. (PMID:34267728)
• Role of GALNT2 on Insulin Sensitivity, Lipid Metabolism and Fat Homeostasis. (PMID:35055114)
• GALNT2 rs4846914 SNP Is Associated with Obesity, Atherogenic Lipid Traits, and ANGPTL3 Plasma Level. (PMID:35885984)
• O-Glycosylating Enzyme GALNT2 Predicts Worse Prognosis in Cervical Cancer. (PMID:36110252)
• GALNT2 promotes invasiveness of colorectal cancer cells partly through AXL. (PMID:36409270)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	galnt2	ENSDARG00000003829
mus_musculus	Galnt2	ENSMUSG00000089704
rattus_norvegicus	Galnt2	ENSRNOG00000019143
drosophila_melanogaster	Pgant2	FBGN0031530
caenorhabditis_elegans		WBGENE00001629

Paralogs (19): GALNT16 (ENSG00000100626), GALNTL5 (ENSG00000106648), GALNT7 (ENSG00000109586), GALNT18 (ENSG00000110328), GALNT3 (ENSG00000115339), GALNT12 (ENSG00000119514), GALNT8 (ENSG00000130035), GALNT15 (ENSG00000131386), GALNT5 (ENSG00000136542), GALNT6 (ENSG00000139629), GALNT1 (ENSG00000141429), GALNT13 (ENSG00000144278), GALNT14 (ENSG00000158089), GALNT10 (ENSG00000164574), GALNTL6 (ENSG00000174473), GALNT11 (ENSG00000178234), GALNT9 (ENSG00000182870), GALNT17 (ENSG00000185274), GALNT4 (ENSG00000257594)

Protein

Protein identifiers

Polypeptide N-acetylgalactosaminyltransferase 2 — Q10471 (reviewed: Q10471)

Alternative names: Polypeptide GalNAc transferase 2, Protein-UDP acetylgalactosaminyltransferase 2, UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 2

All UniProt accessions (2): Q10471, A0A1L7NY50

UniProt curated annotations — full annotation on UniProt →

Function. 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. Has a broad spectrum of substrates for peptides such as EA2, Muc5AC, Muc1a, Muc1b. Probably involved in O-linked glycosylation of the immunoglobulin A1 (IgA1) hinge region. Involved in O-linked glycosylation of APOC-III, ANGPTL3 and PLTP. It participates in the regulation of HDL-C metabolism.

Subcellular location. Golgi apparatus. Golgi stack membrane. Secreted.

Tissue specificity. Detected in urine (at protein level). Widely expressed.

Disease relevance. Congenital disorder of glycosylation 2T (CDG2T) [MIM:618885] A form of congenital disorder of glycosylation, a genetically heterogeneous group of multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG2T is an autosomal recessive form characterized by global developmental delay, intellectual disability with language deficit, autistic features, behavioral abnormalities, epilepsy, chronic insomnia, white matter changes on brain imaging, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding. The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q10471-1	1	yes
Q10471-2	2

RefSeq proteins (2): NP_001278795, NP_004472* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000772	Ricin_B_lectin	Domain
IPR001173	Glyco_trans_2-like	Domain
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily
IPR035992	Ricin_B-like_lectins	Homologous_superfamily
IPR045885	GalNAc-T	Domain

Pfam: PF00535, PF00652

Enzyme classification (BRENDA):

• EC 2.4.1.41 — polypeptide N-acetylgalactosaminyltransferase (BRENDA: 21 organisms, 537 substrates, 86 inhibitors, 206 Km, 52 kcat entries)

Substrate kinetics (BRENDA)

71 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UDP-GALNAC	0.0017–16	32
UDP-N-ACETYL-D-GALACTOSAMINE	0.008–0.081	11
PTTDSTTPAPTTK	0.042–1.02	7
GTTPSPVPTTSTTSAP	0.0259–0.344	5
MUC5AC-13	0.018–0.77	5
MUC5AC-3	0.033–0.107	5
STPSTPSTPSTPSTP	0.2–0.65	5
CPPTPSATTPAPPSSSAPPETTAA	0.01–0.48	4
DSTTPAPTTK	0.07–2.19	4
GTTPSPVPTTST[GALNAC]TSAP	0.115–0.46	4
GT[GALNAC]TPSPVPTTSTTSAP	0.035–0.332	4
UDP-GAL	0.027–0.041	4
GVVPTVVPG	1.74–17.6	3
IGA HINGE	0.01–0.02	3
IGA HINGE-4GALNAC	0.12–0.81	3

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + UDP-N-acetyl-alpha-D-galactosamine = a 3-O-[N-acetyl-alpha-D-galactosaminyl]-L-seryl-[protein] + UDP + H(+) (RHEA:23956)
• L-threonyl-[protein] + UDP-N-acetyl-alpha-D-galactosamine = a 3-O-[N-acetyl-alpha-D-galactosaminyl]-L-threonyl-[protein] + UDP + H(+) (RHEA:52424)

UniProt features (106 total): strand 25, helix 25, binding site 11, sequence conflict 9, sequence variant 8, disulfide bond 5, turn 5, splice variant 3, region of interest 3, chain 2, topological domain 2, mutagenesis site 2, site 1, modified residue 1, glycosylation site 1, transmembrane region 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
5AJO	X-RAY DIFFRACTION	1.48
2FFU	X-RAY DIFFRACTION	1.64
5AJP	X-RAY DIFFRACTION	1.65
5AJN	X-RAY DIFFRACTION	1.67
6E7I	X-RAY DIFFRACTION	1.8
5FV9	X-RAY DIFFRACTION	2.07
4D0Z	X-RAY DIFFRACTION	2.2
5NDF	X-RAY DIFFRACTION	2.3
4D0T	X-RAY DIFFRACTION	2.45
6EGS	X-RAY DIFFRACTION	2.7
2FFV	X-RAY DIFFRACTION	2.75
4D11	X-RAY DIFFRACTION	2.85
6NQT	X-RAY DIFFRACTION	3.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q10471-F1	90.27	0.81

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 516 (not glycosylated)

Ligand- & substrate-binding residues (11): 143; 176; 201; 224; 225; 226; 331; 359; 362; 365; 367

Post-translational modifications (1): 536

Disulfide bonds (5): 126–354, 345–423, 456–473, 496–513, 539–555

Glycosylation sites (1): 29

Mutagenesis-validated functional residues (2):

Position	Phenotype
282	loss of enzyme activity.
361	loss of enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6811436	COPI-independent Golgi-to-ER retrograde traffic
R-HSA-913709	O-linked glycosylation of mucins

MSigDB gene sets: 389 (showing top): ATACCTC_MIR202, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, KYNG_DNA_DAMAGE_DN, REACTOME_MEMBRANE_TRAFFICKING, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, MAHAJAN_RESPONSE_TO_IL1A_DN, GOBP_REGULATION_OF_IMMUNOGLOBULIN_PRODUCTION, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, GOBP_PROTEIN_MATURATION, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, MORF_PPP5C, GOBP_IMMUNOGLOBULIN_PRODUCTION

GO Biological Process (7): positive regulation of immunoglobulin production (GO:0002639), protein O-linked glycosylation (GO:0006493), protein O-linked glycosylation via N-acetylgalactosamine (GO:0016266), protein maturation (GO:0051604), obsolete protein glycosylation (GO:0006486), obsolete protein O-linked glycosylation via serine (GO:0018242), obsolete protein O-linked glycosylation via threonine (GO:0018243)

GO Molecular Function (7): polypeptide N-acetylgalactosaminyltransferase activity (GO:0004653), manganese ion binding (GO:0030145), carbohydrate binding (GO:0030246), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), metal ion binding (GO:0046872)

GO Cellular Component (8): Golgi membrane (GO:0000139), extracellular region (GO:0005576), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), Golgi stack (GO:0005795), membrane (GO:0016020), Golgi cisterna membrane (GO:0032580), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Golgi-to-ER retrograde transport	1
O-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
organelle membrane	2
cytoplasm	2
immunoglobulin production	1
regulation of immunoglobulin production	1
positive regulation of production of molecular mediator of immune response	1
glycoprotein biosynthetic process	1
protein O-linked glycosylation	1
gene expression	1
protein metabolic process	1
acetylgalactosaminyltransferase activity	1
catalytic activity, acting on a protein	1
transition metal ion binding	1
catalytic activity	1
transferase activity	1
cation binding	1
Golgi apparatus	1
bounding membrane of organelle	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endomembrane system	1
intracellular membrane-bounded organelle	1
Golgi apparatus subcompartment	1
Golgi cisterna	1

Protein interactions and networks

STRING

1170 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GALNT2	B4GALNT1	Q00973	815
GALNT2	CACNA1A	P78510	768
GALNT2	C1GALT1	Q9NS00	747
GALNT2	CHPF	Q8IZ52	656
GALNT2	MMAB	Q96EY8	643
GALNT2	ANGPTL3	Q9Y5C1	623
GALNT2	TRIB1	Q96RU8	620
GALNT2	LIPG	Q9Y5X9	605
GALNT2	LIPC	P11150	598
GALNT2	APOA5	Q6Q788	598
GALNT2	CETP	P11597	595
GALNT2	TTC39B	Q5VTQ0	583
GALNT2	CILP2	Q8IUL8	579
GALNT2	C1GALT1C1	Q96EU7	575
GALNT2	GOLPH3L	Q9H4A5	554

IntAct

127 interactions, top by confidence:

A	B	Type	Score
KASH5	GALNT2	psi-mi:“MI:0915”(physical association)	0.720
GALNT2	KASH5	psi-mi:“MI:0915”(physical association)	0.720
STX5	GOSR2	psi-mi:“MI:0914”(association)	0.670
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
SLC12A2	CLGN	psi-mi:“MI:0914”(association)	0.640
GALNT2	BCL2L13	psi-mi:“MI:0915”(physical association)	0.560
COQ9	GALNT2	psi-mi:“MI:0915”(physical association)	0.560
GALNT2	MRM3	psi-mi:“MI:0915”(physical association)	0.560
PEX19	FAM20B	psi-mi:“MI:0914”(association)	0.530
TGOLN2	DENND11	psi-mi:“MI:0914”(association)	0.530
PEX19	MYO1D	psi-mi:“MI:0914”(association)	0.530
NOD2	GALNT2	psi-mi:“MI:0915”(physical association)	0.510
TGOLN2	PGRMC1	psi-mi:“MI:0914”(association)	0.420
Papss1	TCOF1	psi-mi:“MI:0914”(association)	0.350
Tor1aip1	PEX10	psi-mi:“MI:0914”(association)	0.350
Shoc2	GABPB1	psi-mi:“MI:0914”(association)	0.350
Mis12		psi-mi:“MI:0914”(association)	0.350
Itgb1	SSR3	psi-mi:“MI:0914”(association)	0.350
Rab5c		psi-mi:“MI:0914”(association)	0.350
Hspa14	TDG	psi-mi:“MI:0914”(association)	0.350
Uso1	SLC30A6	psi-mi:“MI:0914”(association)	0.350
REEP5	CNOT1	psi-mi:“MI:0914”(association)	0.350
PTPN1		psi-mi:“MI:0914”(association)	0.350
MMGT1	DERL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (164): CCDC155 (Two-hybrid), GALNT2 (Affinity Capture-MS), GALNT2 (Affinity Capture-MS), GALNT2 (Affinity Capture-MS), GALNT2 (Affinity Capture-MS), GALNT2 (Affinity Capture-MS), GALNT2 (Affinity Capture-MS), GALNT2 (Affinity Capture-MS), GALNT2 (Affinity Capture-MS), GALNT2 (Affinity Capture-MS), GALNT2 (Affinity Capture-MS), GALNT2 (Affinity Capture-MS), GALNT2 (Affinity Capture-MS), GALNT2 (Affinity Capture-MS), GALNT2 (Affinity Capture-MS)

ESM2 similar proteins: A2AJ15, B2GUY0, O02773, O18498, O60476, P32906, P33908, P39098, P45700, P45701, P53624, Q08463, Q10471, Q18788, Q1L8D2, Q2HXL6, Q49A17, Q5EA41, Q5GF25, Q5RFJ6, Q6GQB9, Q6NXH2, Q6P9S7, Q6PB93, Q6WV16, Q80VA0, Q86SF2, Q86SR1, Q8BJT9, Q8H116, Q8J0Q0, Q8K1B9, Q8N428, Q925R7, Q925U4, Q92611, Q93Y37, Q9BV94, Q9BZQ6, Q9C512

Diamond homologs: A8Y236, H0ZAB5, O08832, O08912, O45293, O45947, O61394, O61397, O88422, P34678, P70419, Q07537, Q10471, Q10472, Q10473, Q14435, Q29121, Q49A17, Q5EA41, Q5RFJ6, Q6DJR8, Q6IS24, Q6P6V1, Q6P9A2, Q6P9S7, Q6PB93, Q6UE39, Q6WV16, Q6WV17, Q6WV19, Q6WV20, Q7K755, Q7TT15, Q7Z4T8, Q7Z7M9, Q80VA0, Q86SF2, Q86SR1, Q8BGT9, Q8BVG5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 157 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Metal ion SLC transporters	5	32.0×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	9	48.6×	5e-11
intracellular zinc ion homeostasis	10	37.0×	5e-11

Disease & clinical

Clinical variants and AI predictions

ClinVar

229 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	5
Uncertain significance	86
Likely benign	81
Benign	21

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
4689509	NC_000001.10:g.(?230202984)(230417869_?)del	Pathogenic
873545	NM_004481.5(GALNT2):c.865C>T (p.Gln289Ter)	Pathogenic
873546	NM_004481.5(GALNT2):c.598C>T (p.Arg200Ter)	Pathogenic
873547	NM_004481.5(GALNT2):c.296dup (p.Tyr99Ter)	Pathogenic
1065626	NM_004481.5(GALNT2):c.623G>A (p.Arg208Gln)	Likely pathogenic
1711244	NM_004481.5(GALNT2):c.1076A>G (p.His359Arg)	Likely pathogenic
4813785	NM_004481.5(GALNT2):c.691G>T (p.Glu231Ter)	Likely pathogenic
873544	NM_004481.5(GALNT2):c.311T>C (p.Phe104Ser)	Likely pathogenic
873548	NM_004481.5(GALNT2):c.629G>C (p.Arg210Pro)	Likely pathogenic

SpliceAI

4458 predictions. Top by Δscore:

Variant	Effect	Δscore
1:230067402:GGAAG:G	donor_gain	1.0000
1:230067403:GAAGG:G	donor_gain	1.0000
1:230067407:G:GA	donor_loss	1.0000
1:230067408:T:G	donor_loss	1.0000
1:230114007:A:AG	donor_gain	1.0000
1:230178307:TCCAG:T	donor_loss	1.0000
1:230178308:CCAG:C	donor_loss	1.0000
1:230178309:CAGGT:C	donor_loss	1.0000
1:230178310:AG:A	donor_loss	1.0000
1:230178311:GGT:G	donor_loss	1.0000
1:230178312:GTACT:G	donor_loss	1.0000
1:230178313:T:A	donor_loss	1.0000
1:230203125:T:A	acceptor_gain	1.0000
1:230203132:TTTAG:T	acceptor_loss	1.0000
1:230203133:TTA:T	acceptor_loss	1.0000
1:230203134:TAG:T	acceptor_loss	1.0000
1:230203135:A:AG	acceptor_gain	1.0000
1:230203135:A:C	acceptor_loss	1.0000
1:230203135:AG:A	acceptor_gain	1.0000
1:230203135:AGG:A	acceptor_gain	1.0000
1:230203136:G:GG	acceptor_gain	1.0000
1:230203136:G:T	acceptor_loss	1.0000
1:230203136:GG:G	acceptor_gain	1.0000
1:230203136:GGG:G	acceptor_gain	1.0000
1:230203136:GGGA:G	acceptor_gain	1.0000
1:230203286:GACCA:G	donor_gain	1.0000
1:230203287:ACCA:A	donor_gain	1.0000
1:230203288:CCA:C	donor_gain	1.0000
1:230203289:CA:C	donor_gain	1.0000
1:230203291:GTA:G	donor_loss	1.0000

AlphaMissense

3777 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:230203226:T:C	F104L	1.000
1:230203227:T:C	F104S	1.000
1:230203228:C:A	F104L	1.000
1:230203228:C:G	F104L	1.000
1:230236015:T:A	C126S	1.000
1:230236016:G:C	C126S	1.000
1:230236405:G:C	D176H	1.000
1:230236406:A:T	D176V	1.000
1:230236725:G:C	G203R	1.000
1:230236725:G:T	G203C	1.000
1:230243306:G:A	G203D	1.000
1:230243309:T:A	L204H	1.000
1:230243309:T:C	L204P	1.000
1:230243369:A:C	D224A	1.000
1:230243369:A:T	D224V	1.000
1:230243371:A:C	S225R	1.000
1:230243373:T:A	S225R	1.000
1:230243373:T:G	S225R	1.000
1:230243374:C:G	H226D	1.000
1:230246085:C:A	P251H	1.000
1:230246091:T:A	I253N	1.000
1:230246093:G:C	D254H	1.000
1:230246093:G:T	D254Y	1.000
1:230246094:A:T	D254V	1.000
1:230246097:T:A	V255D	1.000
1:230246142:T:C	L270S	1.000
1:230246147:G:C	G272R	1.000
1:230246147:G:T	G272C	1.000
1:230246148:G:A	G272D	1.000
1:230249184:G:A	G273D	1.000

dbSNP variants (sampled 300 via entrez): RS1000009103 (1:230157889 T>G), RS1000034603 (1:230237531 G>C), RS1000039982 (1:230085343 G>A,C), RS1000042004 (1:230195273 G>T), RS1000052215 (1:230154130 T>C), RS1000065088 (1:230275388 A>G), RS1000065905 (1:230163619 G>A), RS1000092800 (1:230222722 A>T), RS1000109498 (1:230080130 AGT>A,AGTGT), RS1000113357 (1:230084715 G>C), RS1000150570 (1:230128302 G>A), RS1000164640 (1:230163430 C>T), RS1000168800 (1:230203893 T>G), RS1000217499 (1:230123983 G>A), RS1000243374 (1:230269442 T>C)

Disease associations

OMIM: gene MIM:602274 | disease phenotypes: MIM:618885

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital disorder of glycosylation, type iit	Strong	Autosomal recessive
congenital disorder of glycosylation	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital disorder of glycosylation, type iit	Strong	AR

Mondo (2): congenital disorder of glycosylation, type iit (MONDO:0030043), congenital disorder of glycosylation (MONDO:0015286)

Orphanet (0):

HPO phenotypes

44 total (30 of 44 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000405	Conductive hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000483	Astigmatism
HP:0000494	Downslanted palpebral fissures
HP:0000639	Nystagmus
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0000817	Reduced eye contact
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001773	Short foot
HP:0001852	Sandal gap
HP:0001891	Iron deficiency anemia
HP:0002019	Constipation
HP:0002194	Delayed gross motor development
HP:0002500	Abnormal cerebral white matter morphology
HP:0003233	Decreased HDL cholesterol concentration
HP:0004322	Short stature
HP:0010804	Tented upper lip vermilion

GWAS associations

123 associations (top):

Study	Trait	p-value
GCST000133_1	HDL cholesterol	2.000000e-13
GCST000135_6	HDL cholesterol	3.000000e-14
GCST000138_3	Triglycerides	7.000000e-15
GCST000139_8	Triglycerides	8.000000e-07
GCST000290_5	HDL cholesterol	4.000000e-08
GCST000755_35	HDL cholesterol	4.000000e-21
GCST000758_10	Triglycerides	2.000000e-14
GCST000805_3	HDL cholesterol	4.000000e-09
GCST001436_17	Metabolic syndrome	4.000000e-08
GCST001639_13	Metabolite levels	1.000000e-09
GCST001813_1	Hematology traits	8.000000e-06
GCST001979_4	Circulating myeloperoxidase levels (serum)	3.000000e-06
GCST002216_27	Triglycerides	7.000000e-31
GCST002223_33	HDL cholesterol	4.000000e-41
GCST002593_1	Dementia and core Alzheimer’s disease neuropathologic changes	2.000000e-06
GCST002593_31	Dementia and core Alzheimer’s disease neuropathologic changes	4.000000e-06
GCST002897_19	Triglycerides	5.000000e-16
GCST002899_26	HDL cholesterol	1.000000e-16
GCST003114_5	Carotid intima media thickness	6.000000e-06
GCST004121_15	Fibrinogen levels	1.000000e-08
GCST004122_12	Fibrinogen levels	8.000000e-07
GCST004232_27	HDL cholesterol levels	5.000000e-08
GCST004232_5	HDL cholesterol levels	2.000000e-44
GCST004237_29	Triglyceride levels	8.000000e-31
GCST004361_9	Estrone/androstenedione ratio in resected early stage-receptor positive breast cancer	8.000000e-06
GCST004603_200	Platelet count	2.000000e-10
GCST004621_44	Red cell distribution width	6.000000e-20
GCST005194_218	Coronary artery disease	7.000000e-06
GCST005196_195	Coronary artery disease	3.000000e-07
GCST006003_6	Triglyceride levels	4.000000e-08

EFO canonical traits (20, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0000195	metabolic syndrome
EFO:0004723	coronary artery calcification
EFO:0005128	albumin:globulin ratio measurement
EFO:0005243	myeloperoxidase measurement
EFO:0006801	Alzheimer’s disease neuropathologic change
EFO:0007970	estrone measurement
EFO:0007972	androstenedione measurement
EFO:0004309	platelet count
EFO:0009188	Red cell distribution width
EFO:0007747	postburn hypertrophic scarring severity measurement
EFO:0004329	alcohol drinking
EFO:0010158	sugar consumption measurement
EFO:0004509	hemoglobin measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018981	Congenital Disorders of Glycosylation	C16.320.565.202.125; C18.452.648.202.125

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3713355 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 126,381 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL288114	GALLIC ACID	2	103,233
CHEMBL6246	ELLAGIC ACID	2	23,148

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2144297	Toxicity	3	atenolol	Hypertension
rs2144300	Other	3	atenolol	Hypertension

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2144297	GALNT2	3	1.00	1	atenolol
rs2144300	GALNT2	3	2.00	1	atenolol

ChEMBL bioactivities

13 potent at pChembl≥5 of 13 total, top 13 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.53	Kd	294	nM	CHEMBL6338
6.43	Kd	371	nM	ELLAGIC ACID
6.29	IC50	510	nM	ELLAGIC ACID
6.12	IC50	760	nM	CHEMBL6338
6.03	Kd	924	nM	GALLIC ACID
5.97	Ki	1068	nM	CHEMBL6338
5.94	IC50	1140	nM	CHEMBL6338
5.90	IC50	1250	nM	CHEMBL6338
5.86	IC50	1370	nM	GALLIC ACID
5.68	IC50	2070	nM	CHEMBL6338
5.53	IC50	2930	nM	ELLAGIC ACID
5.51	IC50	3120	nM	CHEMBL6338
5.21	Ki	6150	nM	CHEMBL6338

PubChem BioAssay actives

13 with measured affinity, of 34 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3,4,8,9-tetrahydroxybenzo[c]chromen-6-one	1588067: Binding affinity of human recombinant FLAG-tagged ppGalNAcT2 expressed in HEK293 cells assessed as dissociation constant by SPR analysis	kd	0.2940	uM
6,7,13,14-tetrahydroxy-2,9-dioxatetracyclo[6.6.2.04,16.011,15]hexadeca-1(15),4,6,8(16),11,13-hexaene-3,10-dione	1588067: Binding affinity of human recombinant FLAG-tagged ppGalNAcT2 expressed in HEK293 cells assessed as dissociation constant by SPR analysis	kd	0.3710	uM
Gallic Acid	1588067: Binding affinity of human recombinant FLAG-tagged ppGalNAcT2 expressed in HEK293 cells assessed as dissociation constant by SPR analysis	kd	0.9240	uM

CTD chemical–gene interactions

57 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
sodium arsenite	affects binding, increases reaction, decreases expression, affects cotreatment, increases abundance	3
Air Pollutants	increases abundance, increases expression, decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Nickel	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Aflatoxin B1	increases methylation, decreases methylation	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
aristolochic acid I	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
2-bromopalmitate	increases palmitoylation, decreases reaction, increases abundance	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	increases methylation	1
1-UFT protocol	decreases response to substance	1
methacrylaldehyde	increases expression, increases abundance, affects cotreatment	1
ciglitazone	affects binding, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
candoxin	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1

ChEMBL screening assays

19 unique, capped per target: 19 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3864103	Binding	Inhibition of ppGalNAcT2 (unknown origin) in presence of OGT, EA2 and UDP-GlcNAc incubated for 25 mins at 37 degC	Discovery of Cell-Permeable O-GlcNAc Transferase Inhibitors via Tethering in Situ Click Chemistry. — J Med Chem

Clinical trials (associated diseases)

9 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT07572825	PHASE1	NOT_YET_RECRUITING	Assessing the Safety and Tolerability of NMN in DHDDS-CDG
NCT02089789	Not specified	RECRUITING	Clinical and Basic Investigations Into Known and Suspected Congenital Disorders of Glycosylation
NCT02503267	Not specified	UNKNOWN	Incidence and Consequences of Disorders of Glycosylation in Patients With Conotruncal and Septal Heart Defects
NCT02955264	Not specified	COMPLETED	Using D-Galactose as a Food Supplement in Congenital Disorders of Glycosylation
NCT03250728	Not specified	COMPLETED	Role of the Endothelium in Stroke-like Episode Among CDG Patients
NCT03560570	Not specified	COMPLETED	Study of Hemostasis in Patients With Congenital Disorder of Glycosylation
NCT04198987	Not specified	COMPLETED	Dietary Monosaccharide Supplementation in Patients With Congenital Disorders of Glycosylation
NCT04199000	Not specified	RECRUITING	Clinical and Basic Investigations Into Congenital Disorders of Glycosylation
NCT04201067	Not specified	COMPLETED	Large-Scale Metabolomic Profiling for the Diagnosis of Inborn Errors of Metabolism