GALNT5

Summary

GALNT5 (polypeptide N-acetylgalactosaminyltransferase 5, HGNC:4127) is a protein-coding gene on chromosome 2q24.1, encoding Polypeptide N-acetylgalactosaminyltransferase 5 (Q7Z7M9). 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.

The protein encoded by this gene is a membrane-bound polypeptide N-acetylgalactosaminyltransferase that is found in the Golgi. The encoded protein catalyzes the first step in the mucin-type O-glycosylation of Golgi proteins, transfering an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor.

Source: NCBI Gene 11227 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 156 total — 1 likely-pathogenic
• MANE Select transcript: NM_014568

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4127
Approved symbol	GALNT5
Name	polypeptide N-acetylgalactosaminyltransferase 5
Location	2q24.1
Locus type	gene with protein product
Status	Approved
Aliases	GalNAc-T5
Ensembl gene	ENSG00000136542
Ensembl biotype	protein_coding
OMIM	615129
Entrez	11227

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000259056, ENST00000461704, ENST00000463418, ENST00000899988, ENST00000953166, ENST00000953167

RefSeq mRNA: 2 — MANE Select: NM_014568 NM_001329868, NM_014568

CCDS: CCDS2203

Canonical transcript exons

ENST00000259056 — 10 exons

Exon	Start	End
ENSE00000778544	157286015	157286134
ENSE00000924647	157295663	157295798
ENSE00000924648	157296394	157296513
ENSE00000924650	157300676	157300999
ENSE00000924651	157305749	157305829
ENSE00000924652	157308567	157308728
ENSE00000964301	157257705	157259536
ENSE00000964302	157311208	157318491
ENSE00000964303	157284282	157284448
ENSE00000964305	157299548	157299665

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 93.61.

FANTOM5 (CAGE): breadth broad, TPM avg 11.4503 / max 640.9709, expressed in 863 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23187	5.3978	692
23185	2.5490	513
23195	0.9036	351
23196	0.4894	238
23194	0.4086	207
23186	0.3551	192
23193	0.2938	151
23190	0.2486	127
23191	0.1556	70
23183	0.1541	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nasal cavity epithelium	UBERON:0005384	93.61	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.56	gold quality
left ventricle myocardium	UBERON:0006566	92.85	gold quality
kidney epithelium	UBERON:0004819	92.53	gold quality
pancreatic ductal cell	CL:0002079	89.62	gold quality
rectum	UBERON:0001052	87.92	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.77	gold quality
colonic mucosa	UBERON:0000317	85.59	gold quality
parotid gland	UBERON:0001831	85.32	silver quality
ileal mucosa	UBERON:0000331	84.84	gold quality
stromal cell of endometrium	CL:0002255	84.29	gold quality
epithelial cell of pancreas	CL:0000083	83.87	silver quality
myocardium	UBERON:0002349	82.90	gold quality
oral cavity	UBERON:0000167	82.70	gold quality
tibia	UBERON:0000979	82.42	gold quality
palpebral conjunctiva	UBERON:0001812	82.37	gold quality
esophagus squamous epithelium	UBERON:0006920	81.62	gold quality
calcaneal tendon	UBERON:0003701	79.34	gold quality
sperm	CL:0000019	79.02	silver quality
minor salivary gland	UBERON:0001830	78.69	gold quality
saliva-secreting gland	UBERON:0001044	78.57	gold quality
cartilage tissue	UBERON:0002418	78.40	gold quality
eye	UBERON:0000970	78.07	gold quality
mouth mucosa	UBERON:0003729	77.74	gold quality
epithelium of mammary gland	UBERON:0003244	77.66	gold quality
mammary duct	UBERON:0001765	77.58	gold quality
secondary oocyte	CL:0000655	76.93	gold quality
vastus lateralis	UBERON:0001379	76.88	gold quality
nasal cavity mucosa	UBERON:0001826	76.83	gold quality
quadriceps femoris	UBERON:0001377	76.27	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.11
E-MTAB-10290	no	632.23

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• of GalNAc-T5 expression in gastric cancer tissues might add some prognostic information for patients with this disease and lead to a more accurate classification under the TNM stage system (PMID:24619076)
• Two identified candidate O-glycoprotein biomarkers (CD44 and GalNAc-T5) circulating with the STn glycoform were further validated as being expressed in gastric cancer tissue (PMID:25813380)
• miR-196b-5p inhibition led to significantly increased colorectal cancer cell migration/invasion and metastases formation in mice, whereas ectopic overexpression showed the opposite phenotype. Molecular profiling and target confirmation identified an interaction between miR-196b-5p and HOXB7 and GALNT5, which in turn regulated colorectal cancer cell migration (PMID:28533224)
• The 5’-end stem-loop motifs of GALNT5 uaRNA promoted the binding of HSP90. (PMID:29743591)
• Oncogenic GALNT5 confers FOLFIRINOX resistance via activating the MYH9/ NOTCH/ DDR axis in pancreatic ductal adenocarcinoma. (PMID:39433745)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000114227
mus_musculus	Galnt5	ENSMUSG00000026828
rattus_norvegicus	Galnt5	ENSRNOG00000004645
drosophila_melanogaster	Pgant5	FBGN0031681
drosophila_melanogaster	Pgant9	FBGN0050463
caenorhabditis_elegans		WBGENE00001628
caenorhabditis_elegans		WBGENE00001630

Paralogs (19): GALNT16 (ENSG00000100626), GALNTL5 (ENSG00000106648), GALNT7 (ENSG00000109586), GALNT18 (ENSG00000110328), GALNT3 (ENSG00000115339), GALNT12 (ENSG00000119514), GALNT8 (ENSG00000130035), GALNT15 (ENSG00000131386), GALNT6 (ENSG00000139629), GALNT1 (ENSG00000141429), GALNT2 (ENSG00000143641), GALNT13 (ENSG00000144278), GALNT14 (ENSG00000158089), GALNT10 (ENSG00000164574), GALNTL6 (ENSG00000174473), GALNT11 (ENSG00000178234), GALNT9 (ENSG00000182870), GALNT17 (ENSG00000185274), GALNT4 (ENSG00000257594)

Protein

Protein identifiers

Polypeptide N-acetylgalactosaminyltransferase 5 — Q7Z7M9 (reviewed: Q7Z7M9)

Alternative names: Polypeptide GalNAc transferase 5, Protein-UDP acetylgalactosaminyltransferase 5, UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 5

All UniProt accessions (1): Q7Z7M9

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 activity toward EA2 peptide substrate, but has a weak activity toward Muc2 or Muc1b substrates.

Subunit / interactions. Interacts with EXT2. Does not interact with EXT1, EXTL1 or EXTL3.

Subcellular location. Golgi apparatus membrane.

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.

RefSeq proteins (2): NP_001316797, NP_055383* (*=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

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 (44 total): glycosylation site 12, binding site 9, disulfide bond 5, region of interest 5, sequence variant 4, topological domain 2, compositionally biased region 2, chain 1, transmembrane region 1, modified residue 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z7M9-F1	68.51	0.46

Functional residue map

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

Ligand- & substrate-binding residues (9): 536; 565; 588; 589; 590; 695; 723; 726; 731

Post-translational modifications (1): 292

Disulfide bonds (5): 486–718, 709–789, 822–835, 858–873, 908–923

Glycosylation sites (12): 217, 256, 273, 316, 362, 395, 406, 578, 776, 827, 845, 912

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-913709	O-linked glycosylation of mucins

MSigDB gene sets: 49 (showing top): ROVERSI_GLIOMA_COPY_NUMBER_UP, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_AMINOGLYCAN_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, chr2q24, WAGNER_APO2_SENSITIVITY, GOBP_AMINOGLYCAN_METABOLIC_PROCESS, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION_VIA_N_ACETYL_GALACTOSAMINE, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, GOMF_ACETYLGALACTOSAMINYLTRANSFERASE_ACTIVITY, GOMF_HEXOSYLTRANSFERASE_ACTIVITY, GOMF_GLYCOSYLTRANSFERASE_ACTIVITY, GOMF_POLYPEPTIDE_N_ACETYLGALACTOSAMINYLTRANSFERASE_ACTIVITY, GOMF_UDP_GLYCOSYLTRANSFERASE_ACTIVITY

GO Biological Process (4): glycosaminoglycan biosynthetic process (GO:0006024), protein O-linked glycosylation (GO:0006493), protein O-linked glycosylation via N-acetylgalactosamine (GO:0016266), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (5): polypeptide N-acetylgalactosaminyltransferase activity (GO:0004653), carbohydrate binding (GO:0030246), metal ion binding (GO:0046872), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

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

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
O-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
aminoglycan biosynthetic process	1
glycosaminoglycan metabolic process	1
glycoprotein biosynthetic process	1
protein O-linked glycosylation	1
acetylgalactosaminyltransferase activity	1
catalytic activity, acting on a protein	1
binding	1
cation binding	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

644 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GALNT5	HOXB7	P09629	595
GALNT5	ST3GAL5	Q9UNP4	492
GALNT5	C1GALT1	Q9NS00	483
GALNT5	ERMN	Q8TAM6	454
GALNT5	HSPBAP1	Q96EW2	454
GALNT5	SEC23IP	Q9Y6Y8	435
GALNT5	ST6GALNAC1	Q9NSC7	429
GALNT5	COPB1	P53618	424
GALNT5	MACO1	Q8N5G2	414
GALNT5	ST8SIA2	Q92186	409
GALNT5	DPYSL4	O14531	403
GALNT5	GCNT3	O95395	398
GALNT5	SEC24A	O95486	383
GALNT5	SEC24D	O94855	376
GALNT5	WDSUB1	Q8N9V3	362

IntAct

22 interactions, top by confidence:

A	B	Type	Score
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
GALNT5	NONO	psi-mi:“MI:0915”(physical association)	0.400
GALNT5	CBLIF	psi-mi:“MI:0915”(physical association)	0.400
	ESYT2	psi-mi:“MI:0914”(association)	0.350
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
TMEM106A	QSOX1	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BRICD5	TMEM131L	psi-mi:“MI:0914”(association)	0.350
NRG1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-DRB1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
ISLR		psi-mi:“MI:0914”(association)	0.350
PDGFRA	QSOX1	psi-mi:“MI:0914”(association)	0.350
CNTNAP3	ADAM10	psi-mi:“MI:0914”(association)	0.350
HLA-DRA	MGRN1	psi-mi:“MI:0914”(association)	0.350
ASGR1	GALNT5	psi-mi:“MI:0914”(association)	0.350

BioGRID (28): GIF (Affinity Capture-MS), GALNT5 (Affinity Capture-MS), GALNT5 (Proximity Label-MS), GALNT5 (Proximity Label-MS), GALNT5 (Affinity Capture-MS), GALNT5 (Affinity Capture-MS), GIF (Affinity Capture-MS), GALNT5 (Two-hybrid), GALNT5 (Reconstituted Complex), GALNT5 (Affinity Capture-MS), GALNT5 (Affinity Capture-MS), GALNT5 (Affinity Capture-MS), GALNT5 (Affinity Capture-MS), GALNT5 (Affinity Capture-MS), GALNT5 (Affinity Capture-MS)

ESM2 similar proteins: A2AMT1, A8MU46, E9PT23, H3JU05, O54963, O70318, O88422, P10636, P10637, P15304, P19332, P46087, P51954, Q13438, Q14028, Q28181, Q3MHX6, Q3UH66, Q3UIZ8, Q3UVR3, Q4ZHG4, Q5I012, Q5RC98, Q5RKH6, Q5S6V2, Q5TCY1, Q5YCV9, Q5YCW0, Q5YCW1, Q6PCF9, Q6PCN3, Q7Z7M9, Q811D2, Q811Q2, Q8BHB9, Q8BWQ5, Q8C102, Q8K2C7, Q91XA2, Q91Z96

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	134
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
814332	GRCh37/hg19 2q24.1(chr2:157117939-158422574)x1	Likely pathogenic

SpliceAI

2131 predictions. Top by Δscore:

Variant	Effect	Δscore
2:157284270:ATTCT:A	acceptor_gain	1.0000
2:157284274:T:TA	acceptor_gain	1.0000
2:157284447:AGG:A	donor_loss	1.0000
2:157284449:G:GA	donor_loss	1.0000
2:157284450:T:G	donor_loss	1.0000
2:157286003:A:AG	acceptor_gain	1.0000
2:157286003:ACTCT:A	acceptor_gain	1.0000
2:157286134:GGTA:G	donor_loss	1.0000
2:157286135:G:T	donor_loss	1.0000
2:157286136:T:G	donor_loss	1.0000
2:157296386:T:TA	acceptor_gain	1.0000
2:157296392:A:AG	acceptor_gain	1.0000
2:157296393:G:GG	acceptor_gain	1.0000
2:157300925:TGCAA:T	donor_gain	1.0000
2:157305743:TTTTA:T	acceptor_loss	1.0000
2:157305744:TTTA:T	acceptor_loss	1.0000
2:157305745:TTA:T	acceptor_loss	1.0000
2:157305746:TAGC:T	acceptor_loss	1.0000
2:157305747:A:AG	acceptor_gain	1.0000
2:157305747:AGCTT:A	acceptor_loss	1.0000
2:157305748:G:GG	acceptor_gain	1.0000
2:157305748:GCTT:G	acceptor_gain	1.0000
2:157305827:GAG:G	donor_gain	1.0000
2:157308561:CCACA:C	acceptor_loss	1.0000
2:157308562:CACAG:C	acceptor_loss	1.0000
2:157308563:ACAG:A	acceptor_loss	1.0000
2:157308564:CA:C	acceptor_loss	1.0000
2:157308565:A:AC	acceptor_loss	1.0000
2:157308565:A:AG	acceptor_gain	1.0000
2:157308566:G:GG	acceptor_gain	1.0000

AlphaMissense

6234 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:157286096:T:C	L568S	1.000
2:157295684:A:C	D588A	1.000
2:157295684:A:T	D588V	1.000
2:157295685:T:A	D588E	1.000
2:157295685:T:G	D588E	1.000
2:157296446:T:C	F644L	1.000
2:157296448:T:A	F644L	1.000
2:157296448:T:G	F644L	1.000
2:157299633:T:A	W695R	1.000
2:157299633:T:C	W695R	1.000
2:157299635:G:C	W695C	1.000
2:157299635:G:T	W695C	1.000
2:157299647:T:A	N699K	1.000
2:157299647:T:G	N699K	1.000
2:157300727:C:G	H723D	1.000
2:157300729:T:A	H723Q	1.000
2:157300729:T:G	H723Q	1.000
2:157300733:T:C	F725L	1.000
2:157300735:C:A	F725L	1.000
2:157300735:C:G	F725L	1.000
2:157300737:G:C	R726T	1.000
2:157300737:G:T	R726I	1.000
2:157300738:A:C	R726S	1.000
2:157300738:A:T	R726S	1.000
2:157300792:C:A	N744K	1.000
2:157300792:C:G	N744K	1.000
2:157300814:T:A	W752R	1.000
2:157300814:T:C	W752R	1.000
2:157259487:A:C	S469R	0.999
2:157259489:C:A	S469R	0.999

dbSNP variants (sampled 300 via entrez): RS1000002853 (2:157278143 T>A), RS1000040614 (2:157275914 G>T), RS1000065718 (2:157308095 A>G), RS1000068143 (2:157266747 A>C), RS1000093618 (2:157308398 T>C), RS1000102106 (2:157275232 C>A,T), RS1000122712 (2:157286853 G>A), RS1000169435 (2:157273102 A>C), RS1000219178 (2:157314749 C>T), RS1000258951 (2:157287208 T>A,C,G), RS1000297302 (2:157260821 C>A,T), RS1000433836 (2:157279174 T>C), RS1000461081 (2:157285527 C>A,T), RS1000512818 (2:157291531 C>A,T), RS1000620265 (2:157279212 A>C)

Disease associations

OMIM: gene MIM:615129 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012311_25	Schizophrenia x sex interaction	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases expression	5
Benzo(a)pyrene	decreases methylation, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
geldanamycin	increases expression	1
urushiol	increases expression	1
methylmercuric chloride	increases expression	1
lasiocarpine	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases methylation, affects cotreatment	1
tobacco tar	decreases expression	1
potassium chromate(VI)	decreases expression	1
CGP 52608	increases reaction, affects binding	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
MRK 003	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Glyphosate	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Cadmium	decreases expression	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	increases expression	1

Clinical trials (associated diseases)

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