GALNT6

Summary

GALNT6 (polypeptide N-acetylgalactosaminyltransferase 6, HGNC:4128) is a protein-coding gene on chromosome 12q13.13, encoding Polypeptide N-acetylgalactosaminyltransferase 6 (Q8NCL4). 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 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes. GalNAc-Ts initiate mucin-type O-linked glycosylation in the Golgi apparatus by catalyzing the transfer of GalNAc to serine and threonine residues on target proteins. They are characterized by an N-terminal transmembrane domain, a stem region, a lumenal catalytic domain containing a GT1 motif and Gal/GalNAc transferase motif, and a C-terminal ricin/lectin-like domain. GalNAc-Ts have different, but overlapping, substrate specificities and patterns of expression. The encoded protein is capable of glycosylating fibronectin peptide in vitro and is expressed in a fibroblast cell line, indicating that it may be involved in the synthesis of oncofetal fibronectin.

Source: NCBI Gene 11226 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 124 total
• Druggable target: yes
• MANE Select transcript: NM_007210

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4128
Approved symbol	GALNT6
Name	polypeptide N-acetylgalactosaminyltransferase 6
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	GalNAc-T6
Ensembl gene	ENSG00000139629
Ensembl biotype	protein_coding
OMIM	605148
Entrez	11226

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 24 protein_coding, 6 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000356317, ENST00000543196, ENST00000603188, ENST00000603203, ENST00000603482, ENST00000603563, ENST00000603641, ENST00000603680, ENST00000604381, ENST00000604426, ENST00000604506, ENST00000604847, ENST00000605055, ENST00000605089, ENST00000605138, ENST00000605367, ENST00000605617, ENST00000605720, ENST00000605822, ENST00000858764, ENST00000858765, ENST00000858766, ENST00000858767, ENST00000858768, ENST00000858769, ENST00000929155, ENST00000929156, ENST00000929157, ENST00000929158, ENST00000929159, ENST00000962797, ENST00000962798

RefSeq mRNA: 1 — MANE Select: NM_007210 NM_007210

CCDS: CCDS8813

Canonical transcript exons

ENST00000356317 — 12 exons

Exon	Start	End
ENSE00000939254	51377195	51377367
ENSE00000939256	51365430	51365579
ENSE00000939258	51364121	51364355
ENSE00000939260	51360721	51360838
ENSE00001283342	51379291	51379884
ENSE00001416669	51391287	51391406
ENSE00001433340	51390850	51390937
ENSE00003462632	51359132	51359332
ENSE00003511510	51358130	51358261
ENSE00003520688	51357349	51357450
ENSE00003527596	51351252	51354492
ENSE00003555082	51355806	51355958

Expression profiles

Bgee: expression breadth ubiquitous, 227 present calls, max score 92.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.0650 / max 70.3332, expressed in 1170 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130966	3.6855	1152
130965	0.2694	150
130962	0.0433	11
130960	0.0395	8
130964	0.0145	3
130963	0.0079	3
130961	0.0050	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	92.84	gold quality
trachea	UBERON:0003126	91.77	gold quality
corpus epididymis	UBERON:0004359	90.83	gold quality
bronchial epithelial cell	CL:0002328	90.10	gold quality
pylorus	UBERON:0001166	89.76	gold quality
jejunal mucosa	UBERON:0000399	89.28	gold quality
duodenum	UBERON:0002114	89.23	gold quality
bronchus	UBERON:0002185	88.82	gold quality
epithelium of bronchus	UBERON:0002031	88.77	gold quality
stromal cell of endometrium	CL:0002255	87.28	gold quality
monocyte	CL:0000576	86.90	gold quality
corpus callosum	UBERON:0002336	86.47	gold quality
mononuclear cell	CL:0000842	86.43	gold quality
leukocyte	CL:0000738	86.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.66	gold quality
granulocyte	CL:0000094	83.86	gold quality
saliva-secreting gland	UBERON:0001044	83.39	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.80	gold quality
cranial nerve II	UBERON:0000941	82.69	gold quality
decidua	UBERON:0002450	81.92	gold quality
minor salivary gland	UBERON:0001830	81.31	gold quality
mammary duct	UBERON:0001765	80.35	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.01	gold quality
ileal mucosa	UBERON:0000331	79.81	gold quality
epithelium of mammary gland	UBERON:0003244	79.53	gold quality
stomach	UBERON:0000945	79.40	gold quality
body of stomach	UBERON:0001161	79.22	gold quality
inferior vagus X ganglion	UBERON:0005363	79.03	gold quality
rectum	UBERON:0001052	78.91	gold quality
nasal cavity mucosa	UBERON:0001826	78.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	98.62
E-ANND-3	yes	10.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

92 targeting GALNT6, 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-3120-5P	100.00	65.56	965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-3934-3P	99.76	65.51	1351

Literature-anchored findings (GeneRIF, showing 18)

• ppGalNAc-T6 is an IHC marker associated with venous invasion in gastric carcinoma and may contribute to the understanding of the molecular mechanisms that underlie aberrant glycosylation in gastric carcinogenesis and in gastric carcinoma. (PMID:18854599)
• Expression of ppGalNAc-T6 is significantly higher in breast cancer compared to ’normal’/benign breast tissue samples. ST6GalNAc-I expression in breast cancer is associated with better prognosis. (PMID:19287074)
• GALNT6-fibronectin pathway should be a critical component for breast cancer development and progression. (PMID:21472136)
• Role of N-acetylgalactosaminyltransferase 6 in early tumorigenesis and formation of metastasis. (PMID:27035742)
• knockdown of GALNT6 caused drastic morphological changes of pancreatic cells, accompanied with the cadherin switching from P-cadherin to E-cadherin. (PMID:27237318)
• GalNAcT6 role in cancer [review] (PMID:27659430)
• These data suggest that excess O-glycosylation on APP by GalNAc-T6 inhibits Abeta production. (PMID:28053144)
• GALNT6-induced O-glycosylation is critical for the stability, subcellular localization, and anti-apoptotic function of GRP78 protein in cancer cells. We also suggest that GRP78 might enhance the activity of GALNT6 in carcinogenesis through driving Golgi-to-ER relocation of GALNT6. (PMID:28110670)
• GALNT6 knockdown decreased phosphorylation of EGFR, whereas GALNT6 overexpression increased the phosphorylation. Results suggest that GALNT6 expression is associated with poor prognosis of ovarian cancer and enhances the aggressive behavior of ovarian cancer cells by regulating EGFR activity. (PMID:28388560)
• Findings show that the expression of GalNAc-T6 in endometrial carcinoma is significantly related to E-cadherin expression, and better prognosis and overall survival. (PMID:28668893)
• Study showed that GalNAc-T6 expression in epithelial ovarian carcinoma was different according to pathological type. In low-grade serous carcinoma, GalNAc-T6 expression may contribute to improved long-term survival. (PMID:28668894)
• these data strongly suggest that aberrant GalNAc-T6 expression and site-specific glycosylation is involved in oncogenic transformation. (PMID:29187600)
• the 15-glycogene signature and the expression levels of GALNT6 mRNA and protein each serve as a novel prognostic biomarker, highlighting the role of dysregulated glycogenes in cancer-associated glycan synthesis and poor prognosis (PMID:29844132)
• O-glycosylation of ER-alpha by GALNT6 in breast cancer cells. (PMID:30208353)
• We confirmed that GALNT3 gene ablation leads to strong and rather compensatory GALNT6 upregulation in EOC cells. Moreover, double GALNT3/T6 suppression was significantly associated with stronger inhibitory effects on EOC cell proliferation, migration, and invasion, and accordingly displayed a significant increase in animal survival rates compared with GALNT3-ablated and control (Ctrl) EOC cells. (PMID:31071912)
• The GALNT6LGALS3BP axis promotes breast cancer cell growth. (PMID:31894262)
• GALNT6 promotes invasion and metastasis of human lung adenocarcinoma cells through O-glycosylating chaperone protein GRP78. (PMID:32393740)
• GALNT6 promotes breast cancer metastasis by increasing mucin-type O-glycosylation of alpha2M. (PMID:32559179)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
mus_musculus	Galnt6	ENSMUSG00000037280
rattus_norvegicus	Galnt6	ENSRNOG00000033059
drosophila_melanogaster	Pgant7	FBGN0030930
drosophila_melanogaster	Pgant5	FBGN0031681
drosophila_melanogaster	Pgant6	FBGN0035375
drosophila_melanogaster	CG7304	FBGN0036527
drosophila_melanogaster	CG7579	FBGN0036528
drosophila_melanogaster	Pgant8	FBGN0036529
drosophila_melanogaster	Pgant9	FBGN0050463
drosophila_melanogaster	CG31776	FBGN0051776
drosophila_melanogaster	Pgant4	FBGN0051956
caenorhabditis_elegans		WBGENE00001628
caenorhabditis_elegans		WBGENE00001630
caenorhabditis_elegans		WBGENE00001632
caenorhabditis_elegans		WBGENE00001635

Paralogs (19): GALNT16 (ENSG00000100626), GALNTL5 (ENSG00000106648), GALNT7 (ENSG00000109586), GALNT18 (ENSG00000110328), GALNT3 (ENSG00000115339), GALNT12 (ENSG00000119514), GALNT8 (ENSG00000130035), GALNT15 (ENSG00000131386), GALNT5 (ENSG00000136542), 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 6 — Q8NCL4 (reviewed: Q8NCL4)

Alternative names: Polypeptide GalNAc transferase 6, Protein-UDP acetylgalactosaminyltransferase 6, UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 6

All UniProt accessions (10): Q8NCL4, S4R310, S4R345, S4R355, S4R370, S4R396, S4R3A9, S4R3L4, S4R3M3, S4R3S5

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. May participate in synthesis of oncofetal fibronectin. Has activity toward MUC1A, MUC2, EA2 and fibronectin peptides. Glycosylates FGF23.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Expressed in placenta and trachea. Weakly expressed in brain and pancreas. Expressed in fibroblast. Weakly or not expressed in lung, liver, muscle, kidney, spleen, thymus, prostate, testis, ovary, intestine, colon, leukocyte, stomach, thyroid, spinal cord, lymph node, trachea, adrenal gland and bone marrow.

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 (1): NP_009141* (*=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 (25 total): binding site 7, disulfide bond 5, sequence conflict 3, topological domain 2, glycosylation site 2, region of interest 2, chain 1, transmembrane region 1, sequence variant 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NCL4-F1	88.62	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.

Ligand- & substrate-binding residues (7): 511; 514; 528; 533; 269; 271; 407

Disulfide bonds (5): 165–402, 393–474, 509–527, 553–566, 597–610

Glycosylation sites (2): 86, 476

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 191 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, ROVERSI_GLIOMA_COPY_NUMBER_UP, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, KOYAMA_SEMA3B_TARGETS_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM3, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, ENGELMANN_CANCER_PROGENITORS_UP, WAGNER_APO2_SENSITIVITY, TIEN_INTESTINE_PROBIOTICS_24HR_UP, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION_VIA_N_ACETYL_GALACTOSAMINE, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION, HUANG_FOXA2_TARGETS_DN

GO Biological Process (4): protein O-linked glycosylation (GO:0006493), protein O-linked glycosylation via N-acetylgalactosamine (GO:0016266), obsolete protein glycosylation (GO:0006486), obsolete protein O-linked glycosylation via threonine (GO:0018243)

GO Molecular Function (6): polypeptide N-acetylgalactosaminyltransferase activity (GO:0004653), carbohydrate binding (GO:0030246), metal ion binding (GO:0046872), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (4): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), perinuclear region of cytoplasm (GO:0048471), 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
binding	2
cytoplasm	2
cellular anatomical structure	2
glycoprotein biosynthetic process	1
protein O-linked glycosylation	1
acetylgalactosaminyltransferase activity	1
catalytic activity, acting on a protein	1
cation binding	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

756 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GALNT6	B4GALNT1	Q00973	847
GALNT6	C1GALT1	Q9NS00	738
GALNT6	FN1	P02751	572
GALNT6	GCNT1	Q02742	525
GALNT6	ST6GALNAC1	Q9NSC7	518
GALNT6	C1GALT1C1	Q96EU7	507
GALNT6	ST3GAL1	Q11201	504
GALNT6	CHST2	Q9Y4C5	496
GALNT6	MUC1	P13931	485
GALNT6	GCNT3	O95395	467
GALNT6	ST6GAL1	P15907	449
GALNT6	B3GNT6	Q6ZMB0	433
GALNT6	MGAT5	Q09328	423
GALNT6	FUT6	P51993	423
GALNT6	ALG12	Q9BV10	418

IntAct

49 interactions, top by confidence:

A	B	Type	Score
GALNT6	RMND1	psi-mi:“MI:0915”(physical association)	0.620
GALNT6	PEX1	psi-mi:“MI:0915”(physical association)	0.560
GALNT6	WFS1	psi-mi:“MI:0915”(physical association)	0.560
GALNT6	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
GALNT6	NDUFS4	psi-mi:“MI:0914”(association)	0.530
RHOBTB3	ARF5	psi-mi:“MI:0914”(association)	0.530
GALNT6	B4GALT3	psi-mi:“MI:0914”(association)	0.530
GALNT6	RPL13	psi-mi:“MI:0915”(physical association)	0.400
ALDOA	GALNT6	psi-mi:“MI:0915”(physical association)	0.370
AK6	GALNT6	psi-mi:“MI:0915”(physical association)	0.370
GALNT6	SLC5A6	psi-mi:“MI:0915”(physical association)	0.370
TMEM9	GALNT6	psi-mi:“MI:0915”(physical association)	0.370
E6	SURF4	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
SCGB2A1	RAP1BL	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
NDST2	CLGN	psi-mi:“MI:0914”(association)	0.350
EDDM3A	PLXNA2	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

BioGRID (96): NDUFAF6 (Affinity Capture-MS), ATP2B3 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS), NDUFB6 (Affinity Capture-MS), SLC30A1 (Affinity Capture-MS), NDUFB8 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), NDUFA12 (Affinity Capture-MS), EDEM1 (Affinity Capture-MS), NDUFS6 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), FAM20B (Affinity Capture-MS), B4GALT3 (Affinity Capture-MS), NDUFB5 (Affinity Capture-MS), NDUFS4 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K1Q8, B2RX12, E9PU17, E9PX95, F1MWM0, O00329, O15438, O35600, O75899, O88563, O88871, O94911, O95477, P41233, P55205, P58428, P78363, Q09427, Q09428, Q09429, Q2NKY8, Q5BJS0, Q5R607, Q5ZI74, Q6TL19, Q7L2E3, Q7TNJ2, Q80T41, Q84M24, Q8CF82, Q8IUA7, Q8K440, Q8K441, Q8K442, Q8K448, Q8K449, Q8LPK0, Q8N139, Q8NCL4, Q8R420

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 61 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	6	88.0×	1e-08
R-HSA-425366	6	26.5×	5e-06
SLC-mediated transmembrane transport	7	10.1×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	9	114.9×	1e-14
intracellular monoatomic cation homeostasis	5	102.1×	9e-08
intracellular zinc ion homeostasis	9	78.8×	2e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	108
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1768 predictions. Top by Δscore:

Variant	Effect	Δscore
12:51354490:ATCC:A	acceptor_loss	1.0000
12:51354491:TCC:T	acceptor_loss	1.0000
12:51354492:CCTA:C	acceptor_loss	1.0000
12:51354493:C:G	acceptor_loss	1.0000
12:51354494:T:A	acceptor_loss	1.0000
12:51357343:GCATA:G	donor_loss	1.0000
12:51357344:CATAC:C	donor_loss	1.0000
12:51357345:ATAC:A	donor_loss	1.0000
12:51357346:TACCT:T	donor_loss	1.0000
12:51357347:A:T	donor_loss	1.0000
12:51357348:CC:C	donor_loss	1.0000
12:51357448:GATCT:G	acceptor_loss	1.0000
12:51357450:TCTGC:T	acceptor_loss	1.0000
12:51357451:C:CC	acceptor_gain	1.0000
12:51357461:G:C	acceptor_gain	1.0000
12:51357461:G:GC	acceptor_gain	1.0000
12:51357466:C:CT	acceptor_gain	1.0000
12:51357467:A:T	acceptor_gain	1.0000
12:51364119:A:AC	donor_gain	1.0000
12:51364120:C:CC	donor_gain	1.0000
12:51365424:ACTC:A	donor_loss	1.0000
12:51365426:TCACA:T	donor_loss	1.0000
12:51365427:CACAG:C	donor_loss	1.0000
12:51365428:A:AC	donor_gain	1.0000
12:51365429:C:CA	donor_gain	1.0000
12:51365429:C:CT	donor_loss	1.0000
12:51365429:CAG:C	donor_gain	1.0000
12:51365576:TGCT:T	acceptor_gain	1.0000
12:51365578:CT:C	acceptor_gain	1.0000
12:51365580:C:CC	acceptor_gain	1.0000

AlphaMissense

4117 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:51359273:G:C	F409L	1.000
12:51359273:G:T	F409L	1.000
12:51359275:A:G	F409L	1.000
12:51359281:G:C	H407D	1.000
12:51360751:C:A	W379C	1.000
12:51360751:C:G	W379C	1.000
12:51360753:A:G	W379R	1.000
12:51360753:A:T	W379R	1.000
12:51357425:C:G	C509S	0.999
12:51357426:A:T	C509S	0.999
12:51359197:A:G	W435R	0.999
12:51359197:A:T	W435R	0.999
12:51359219:A:C	N427K	0.999
12:51359219:A:T	N427K	0.999
12:51359274:A:C	F409C	0.999
12:51359279:A:C	H407Q	0.999
12:51359279:A:T	H407Q	0.999
12:51359280:T:C	H407R	0.999
12:51359280:T:G	H407P	0.999
12:51359281:G:T	H407N	0.999
12:51359283:C:T	G406D	0.999
12:51360722:C:G	R389P	0.999
12:51360728:G:A	S387F	0.999
12:51360739:G:C	N383K	0.999
12:51360739:G:T	N383K	0.999
12:51360743:T:A	E382V	0.999
12:51360815:A:G	L358P	0.999
12:51360815:A:T	L358H	0.999
12:51360824:G:T	A355D	0.999
12:51364177:C:A	W331C	0.999

dbSNP variants (sampled 300 via entrez): RS1000074213 (12:51367524 G>A), RS1000135512 (12:51362924 C>G,T), RS1000260094 (12:51372635 C>G,T), RS1000289636 (12:51372949 G>A,T), RS1000300256 (12:51361136 A>G), RS1000324659 (12:51353635 G>T), RS1000437908 (12:51366565 C>A), RS1000440828 (12:51353931 G>A), RS1000487835 (12:51379054 C>T), RS1000525603 (12:51374611 C>A), RS1000576597 (12:51374278 C>G), RS1000667935 (12:51355170 G>A,C), RS1000783621 (12:51355555 C>T), RS1000892472 (12:51391956 G>A), RS1001051727 (12:51391273 T>A)

Disease associations

OMIM: gene MIM:605148 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST010105_132	Nicotine dependence symptom count	3.000000e-06
GCST010136_14	Fruit consumption	2.000000e-08
GCST010204_126	Low density lipoprotein cholesterol levels	2.000000e-11
GCST90013442_20	Keratoconus	7.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009262	nicotine dependence symptom count
EFO:0008111	diet measurement
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523400 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.74	IC50	1830	nM	CHEMBL6338

PubChem BioAssay actives

1 with measured affinity, of 1 total; 1 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	1588076: Inhibition of catalytic activity of ppGalNAcT6 (unknown origin) using EA2 peptide as substrate incubated for 30 mins by HPLC-based enzyme assay	ic50	1.8300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression	2
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Nickel	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	affects expression	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
terbufos	decreases methylation	1
afimoxifene	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	decreases methylation	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Leflunomide	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Aldehydes	increases expression	1
Atrazine	increases expression	1
Cadmium	decreases expression, increases abundance	1
Calcitriol	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4386621	Binding	Inhibition of catalytic activity of ppGalNAcT6 (unknown origin) using EA2 peptide as substrate incubated for 30 mins by HPLC-based enzyme assay	Inhibition of polypeptide N-acetyl-α-galactosaminyltransferases is an underlying mechanism of dietary polyphenols preventing colorectal tumorigenesis. — Bioorg Med Chem

Clinical trials (associated diseases)

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