A4GNT

Summary

A4GNT (alpha-1,4-N-acetylglucosaminyltransferase, HGNC:17968) is a protein-coding gene on chromosome 3q22.3, encoding Alpha-1,4-N-acetylglucosaminyltransferase (Q9UNA3). Catalyzes the transfer of N-acetylglucosamine (GlcNAc) residues from UDP-N-acetyl-alpha-D-glucosamine donnors to beta (1->4)-linked or beta-(1->3)-linked galactose residues on O-glycans like core 2 branched O-glycans.

This gene encodes a protein from the glycosyltransferase 32 family. The enzyme catalyzes the transfer of N-acetylglucosamine (GlcNAc) to core 2 branched O-glycans. It forms a unique glycan, GlcNAcalpha1–>4Galbeta–>R and is largely associated with the Golgi apparatus membrane.

Source: NCBI Gene 51146 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 76 total — 12 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_016161

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17968
Approved symbol	A4GNT
Name	alpha-1,4-N-acetylglucosaminyltransferase
Location	3q22.3
Locus type	gene with protein product
Status	Approved
Aliases	alpha4GnT
Ensembl gene	ENSG00000118017
Ensembl biotype	protein_coding
OMIM	616709
Entrez	51146

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000236709, ENST00000858667

RefSeq mRNA: 1 — MANE Select: NM_016161 NM_016161

CCDS: CCDS3097

Canonical transcript exons

ENST00000236709 — 3 exons

Exon	Start	End
ENSE00001037446	138123713	138124878
ENSE00001241635	138132212	138132390
ENSE00001241655	138130849	138131282

Expression profiles

Bgee: expression breadth broad, 89 present calls, max score 82.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0299 / max 22.0695, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44750	0.0299	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pylorus	UBERON:0001166	82.82	gold quality
pancreatic ductal cell	CL:0002079	79.14	silver quality
body of pancreas	UBERON:0001150	71.58	gold quality
metanephros cortex	UBERON:0010533	65.90	gold quality
tibialis anterior	UBERON:0001385	65.36	silver quality
body of stomach	UBERON:0001161	64.22	gold quality
stomach	UBERON:0000945	64.07	gold quality
gall bladder	UBERON:0002110	63.39	gold quality
pancreas	UBERON:0001264	60.92	gold quality
ileal mucosa	UBERON:0000331	57.43	silver quality
deltoid	UBERON:0001476	57.16	gold quality
metanephros	UBERON:0000081	56.40	gold quality
fundus of stomach	UBERON:0001160	56.36	gold quality
skin of hip	UBERON:0001554	56.13	silver quality
duodenum	UBERON:0002114	55.74	gold quality
stromal cell of endometrium	CL:0002255	52.41	silver quality
cortex of kidney	UBERON:0001225	52.09	gold quality
quadriceps femoris	UBERON:0001377	49.81	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	49.23	silver quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
adult mammalian kidney	UBERON:0000082	48.57	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
oviduct epithelium	UBERON:0004804	48.54	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

54 targeting A4GNT, 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-4482-3P	99.98	72.50	3147
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-106A-3P	99.53	67.58	995
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891

Literature-anchored findings (GeneRIF, showing 2)

• Up-regulation of alpha-1,4-N-acetylglucosaminyltransferase is associated with pancreatic cancer (PMID:16441422)
• human alpha1,4-N-acetylglucosaminyltransferase (alpha4GnT) is responsible for O-glycan biosynthesis and has a role in preventing gastric cancer by inhibiting H. pylori infection and also suppressing tumor-promoting inflammation (PMID:22307328)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	A4gnt	ENSMUSG00000037953
rattus_norvegicus	A4gnt	ENSRNOG00000042649
drosophila_melanogaster	alpha4GT1	FBGN0031491
drosophila_melanogaster	alpha4GT2	FBGN0039378
caenorhabditis_elegans		WBGENE00015309

Paralogs (1): A4GALT (ENSG00000128274)

Protein

Protein identifiers

Alpha-1,4-N-acetylglucosaminyltransferase — Q9UNA3 (reviewed: Q9UNA3)

All UniProt accessions (1): Q9UNA3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of N-acetylglucosamine (GlcNAc) residues from UDP-N-acetyl-alpha-D-glucosamine donnors to beta (1->4)-linked or beta-(1->3)-linked galactose residues on O-glycans like core 2 branched O-glycans. Necessary for the synthesis of type III mucin which is specifically produced in the stomach, duodenum, and pancreatic duct. May protect against inflammation-associated gastric adenocarcinomas.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Detected in stomach and pancreas.

Domain organisation. The conserved DXD motif is involved in enzyme activity.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 32 family.

RefSeq proteins (1): NP_057245* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007577	GlycoTrfase_DXD_sugar-bd_CS	Conserved_site
IPR007652	A1-4-GlycosylTfrase_dom	Domain
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily
IPR051981	A4GCT	Family

Pfam: PF04488, PF04572

Catalyzed reactions (Rhea), 5 shown:

• a beta-D-galactoside + UDP-N-acetyl-alpha-D-glucosamine = an N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-galactosyl derivative + UDP + H(+) (RHEA:85983)
• a 3-O-{beta-D-galactosyl-(1->3)-[N-acetyl-beta-D-glucosaminyl-(1->6)]-N-acetyl-alpha-D-galactosaminyl}-L-threonyl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = a 3-O-{alpha-D-GlcNAc-(1->4)-beta-D-Gal-(1->3)-[beta-D-GlcNAc-(1->6)]-alpha-D-GalNAc}-L-threonyl-[protein] + UDP + H(+) (RHEA:86035)
• a 3-O-{beta-D-Gal-(1->3)-[beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->6)]-alpha-D-GalNAc}-L-threonyl-[protein] + 2 UDP-N-acetyl-alpha-D-glucosamine = a 3-O-{alpha-D-GlcNAc-(1->4)-beta-D-Gal-(1->3)-[alpha-D-GlcNAc-(1->4)-beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->6)]-alpha-D-GalNAc}-L-threonyl-[protein] + 2 UDP + 2 H(+) (RHEA:86039)
• a 3-O-{beta-D-Gal-(1->3)-[beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->6)]-alpha-D-GalNAc}-L-seryl-[protein] + 2 UDP-N-acetyl-alpha-D-glucosamine = a 3-O-{alpha-D-GlcNAc-(1->4)-beta-D-Gal-(1->3)-[alpha-D-GlcNAc-(1->4)-beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->6)]-alpha-D-GalNAc}-L-seryl-[protein] + 2 UDP + 2 H(+) (RHEA:86043)
• 3-O-{beta-D-galactosyl-(1->3)-[N-acetyl-beta-D-glucosaminyl-(1->6)]-N-acetyl-alpha-D-galactosaminyl}-L-seryl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = a 3-O-{alpha-D-GlcNAc-(1->4)-beta-D-Gal-(1->3)-[beta-D-GlcNAc-(1->6)]-alpha-D-GalNAc}-L-seryl-[protein] + UDP + H(+) (RHEA:86059)

UniProt features (10 total): glycosylation site 4, topological domain 2, chain 1, transmembrane region 1, short sequence motif 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UNA3-F1	89.43	0.77

Functional residue map

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

Glycosylation sites (4): 99, 138, 251, 282

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-913709	O-linked glycosylation of mucins
R-HSA-392499	Metabolism of proteins
R-HSA-5173105	O-linked glycosylation
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 61 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_EPITHELIAL_CELL_PROLIFERATION, chr3q22, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION_VIA_N_ACETYL_GALACTOSAMINE, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, GOMF_HEXOSYLTRANSFERASE_ACTIVITY, GOMF_GLYCOSYLTRANSFERASE_ACTIVITY, GOMF_UDP_GLYCOSYLTRANSFERASE_ACTIVITY, GOMF_ACETYLGLUCOSAMINYLTRANSFERASE_ACTIVITY

GO Biological Process (7): carbohydrate metabolic process (GO:0005975), protein O-linked glycosylation (GO:0006493), glycoprotein biosynthetic process (GO:0009101), protein O-linked glycosylation via N-acetylgalactosamine (GO:0016266), epithelial cell proliferation (GO:0050673), negative regulation of epithelial cell proliferation (GO:0050680), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (4): acetylglucosaminyltransferase activity (GO:0008375), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), hexosyltransferase activity (GO:0016758)

GO Cellular Component (3): Golgi membrane (GO:0000139), membrane (GO:0016020), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
O-linked glycosylation	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	1
glycoprotein biosynthetic process	1
macromolecule biosynthetic process	1
glycoprotein metabolic process	1
carbohydrate derivative biosynthetic process	1
protein O-linked glycosylation	1
cell population proliferation	1
negative regulation of cell population proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
UDP-glycosyltransferase activity	1
hexosyltransferase activity	1
catalytic activity	1
transferase activity	1
glycosyltransferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

564 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
A4GNT	MUC6	Q6W4X9	744
A4GNT	GCNT4	Q9P109	724
A4GNT	C1GALT1	Q9NS00	577
A4GNT	GCNT3	O95395	533
A4GNT	GCNT1	Q02742	506
A4GNT	GKN1	Q9NS71	500
A4GNT	B3GNT3	Q9Y2A9	458
A4GNT	EXTL3	O43909	454
A4GNT	MUC5AC	P98088	443
A4GNT	CSGALNACT2	Q8N6G5	404
A4GNT	RNF151	Q2KHN1	397
A4GNT	CHPF	Q8IZ52	396
A4GNT	EXT2	Q93063	396
A4GNT	METTL24	Q5JXM2	394
A4GNT	PRXL2C	Q7RTV5	389

IntAct

7 interactions, top by confidence:

A	B	Type	Score
A4GNT	POTEF	psi-mi:“MI:0914”(association)	0.530
FANK1	UBXN2B	psi-mi:“MI:0914”(association)	0.350
PRSS48	UBXN2B	psi-mi:“MI:0914”(association)	0.350
A4GNT	CLGN	psi-mi:“MI:0914”(association)	0.350

BioGRID (71): POMT1 (Affinity Capture-MS), GP1BB (Affinity Capture-MS), LMF2 (Affinity Capture-MS), POTEF (Affinity Capture-MS), IMPA2 (Affinity Capture-MS), FAM213A (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), PDXDC1 (Affinity Capture-MS), ARF5 (Affinity Capture-MS), FAM69A (Affinity Capture-MS), TMEM206 (Affinity Capture-MS), BLK (Affinity Capture-MS), FAM3C (Affinity Capture-MS), ICK (Affinity Capture-MS), COMMD3 (Affinity Capture-MS)

ESM2 similar proteins: A0A4Z3, A1Y9I9, A4FUH1, B6CZ46, B6CZ56, B6CZ62, D3ZNQ3, G3V9Q9, O43505, O60512, O60909, O94766, P14616, P14617, P58158, Q09326, Q10469, Q2NKH9, Q2YDM8, Q3V1N9, Q3V5L5, Q4R5T7, Q5EA01, Q5EB73, Q5JU69, Q5M936, Q5NVN3, Q5R4S2, Q5R868, Q5YB40, Q5ZLK4, Q64716, Q6AYR4, Q765H6, Q7Z4J2, Q8BGT9, Q8BWP8, Q8IXK2, Q8NCL4, Q8R1J9

Diamond homologs: O14084, P0C8Q4, P31755, P33300, P38287, Q10323, Q5A4E3, Q9UNA3, Q9UT67, Q14BT6, Q67BJ4, Q9JI93, Q9N289, Q9N290, Q9N291, Q9NPC4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	1
Uncertain significance	55
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
145313	GRCh38/hg38 3q22.3-24(chr3:137932000-144468739)x1	Pathogenic
147358	GRCh38/hg38 3q22.1-24(chr3:129817243-143381624)x1	Pathogenic
149077	GRCh38/hg38 3q22.2-25.1(chr3:134257180-149729538)x1	Pathogenic
150251	GRCh38/hg38 3q22.3-24(chr3:137991123-143618786)x1	Pathogenic
150380	GRCh38/hg38 3q22.1-23(chr3:130401265-139005019)x1	Pathogenic
151765	GRCh38/hg38 3q22.2-23(chr3:134333553-141701458)x1	Pathogenic
152454	GRCh38/hg38 3q22.1-23(chr3:129817243-141425155)x1	Pathogenic
155567	GRCh38/hg38 3q22.1-24(chr3:132716978-144784743)x1	Pathogenic
2426786	NC_000003.11:g.(?137781658)(138665815_?)del	Pathogenic
4279237	GRCh37/hg19 3q22.1-25.1(chr3:131235568-150065289)x1	Pathogenic
57832	GRCh38/hg38 3q22.2-24(chr3:135227451-145870770)x1	Pathogenic
625695	GRCh37/hg19 3q22.2-24(chr3:135288025-146874012)	Pathogenic
253333	GRCh37/hg19 3q22.3-23(chr3:135935129-141867748)x3	Likely pathogenic

SpliceAI

475 predictions. Top by Δscore:

Variant	Effect	Δscore
3:138130847:A:AC	donor_gain	1.0000
3:138130848:C:CC	donor_gain	1.0000
3:138124879:C:CC	acceptor_gain	0.9900
3:138124874:TTGAT:T	acceptor_gain	0.9700
3:138124875:TGAT:T	acceptor_gain	0.9700
3:138124877:ATCT:A	acceptor_loss	0.9700
3:138124878:TC:T	acceptor_loss	0.9700
3:138124879:C:CA	acceptor_loss	0.9700
3:138130841:ACACT:A	donor_loss	0.9700
3:138130842:CACT:C	donor_loss	0.9700
3:138130843:ACTTA:A	donor_loss	0.9700
3:138130844:CT:C	donor_loss	0.9700
3:138130845:TTACT:T	donor_loss	0.9700
3:138130846:TA:T	donor_loss	0.9700
3:138130847:AC:A	donor_loss	0.9700
3:138130848:CTTGA:C	donor_gain	0.9600
3:138124913:C:CT	acceptor_gain	0.9400
3:138132341:A:C	donor_gain	0.9400
3:138124888:C:CT	acceptor_gain	0.9300
3:138132132:A:AC	donor_gain	0.9200
3:138124876:GAT:G	acceptor_gain	0.9000
3:138124913:C:T	acceptor_gain	0.9000
3:138131181:T:TA	donor_gain	0.9000
3:138124904:CCAAG:C	acceptor_gain	0.8900
3:138130840:AACAC:A	donor_loss	0.8900
3:138130848:CTTG:C	donor_gain	0.8900
3:138124877:AT:A	acceptor_gain	0.8800
3:138124882:C:CT	acceptor_gain	0.8800
3:138130504:G:C	acceptor_gain	0.8800
3:138131872:A:C	donor_gain	0.8800

AlphaMissense

2247 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:138131040:A:G	S73P	0.982
3:138124787:T:A	D167V	0.981
3:138124826:C:G	R154P	0.980
3:138131034:C:G	A75P	0.980
3:138124781:T:A	D169V	0.976
3:138124786:G:C	D167E	0.974
3:138124786:G:T	D167E	0.974
3:138124827:G:T	R154S	0.973
3:138131050:A:C	C69W	0.973
3:138124340:C:G	C316S	0.972
3:138124341:A:T	C316S	0.972
3:138124425:G:C	H288D	0.972
3:138124714:A:C	S191R	0.972
3:138124714:A:T	S191R	0.972
3:138124716:T:G	S191R	0.972
3:138124802:C:A	G162V	0.971
3:138124419:A:G	W290R	0.970
3:138124419:A:T	W290R	0.970
3:138131036:G:T	A74D	0.969
3:138131039:G:A	S73F	0.969
3:138131051:C:G	C69S	0.969
3:138131052:A:G	C69R	0.969
3:138131052:A:T	C69S	0.969
3:138131051:C:T	C69Y	0.968
3:138131096:A:G	F54S	0.968
3:138124339:A:C	C316W	0.967
3:138124780:A:C	D169E	0.965
3:138124780:A:T	D169E	0.965
3:138124417:C:A	W290C	0.960
3:138124417:C:G	W290C	0.960

dbSNP variants (sampled 300 via entrez): RS1000432199 (3:138128500 T>G), RS1000455624 (3:138129216 C>T), RS1000627193 (3:138134053 T>C), RS1000733559 (3:138126173 G>A), RS1000757085 (3:138127916 G>A), RS1000824686 (3:138129589 C>T), RS1001104531 (3:138127595 C>A,T), RS1001685261 (3:138134061 G>A), RS1002022276 (3:138132357 G>A,C,T), RS1002074608 (3:138132554 G>A), RS1002265097 (3:138132799 CAA>C), RS1002375316 (3:138125836 C>G), RS1002758031 (3:138124622 T>C), RS1003506775 (3:138123988 A>C,G), RS1004638423 (3:138131773 A>G)

Disease associations

OMIM: gene MIM:616709 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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