GALNTL6

Summary

GALNTL6 (polypeptide N-acetylgalactosaminyltransferase like 6, HGNC:33844) is a protein-coding gene on chromosome 4q34.1, encoding Polypeptide N-acetylgalactosaminyltransferase-like 6 (Q49A17). 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.

Enables polypeptide N-acetylgalactosaminyltransferase activity. Involved in protein O-linked glycosylation via threonine. Predicted to be located in Golgi membrane. Predicted to be active in Golgi apparatus.

Source: NCBI Gene 442117 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 171 total
• MANE Select transcript: NM_001034845

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33844
Approved symbol	GALNTL6
Name	polypeptide N-acetylgalactosaminyltransferase like 6
Location	4q34.1
Locus type	gene with protein product
Status	Approved
Aliases	GALNT17, GalNAc-T6L
Ensembl gene	ENSG00000174473
Ensembl biotype	protein_coding
OMIM	615138
Entrez	442117

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding_CDS_not_defined, 3 protein_coding

ENST00000457021, ENST00000504379, ENST00000506823, ENST00000508122, ENST00000511251, ENST00000513061

RefSeq mRNA: 1 — MANE Select: NM_001034845 NM_001034845

CCDS: CCDS34104

Canonical transcript exons

ENST00000506823 — 13 exons

Exon	Start	End
ENSE00001207947	172952037	172952258
ENSE00001207953	172931161	172931268
ENSE00001207963	172813540	172813723
ENSE00001216189	173021476	173021625
ENSE00001319125	173009178	173009294
ENSE00001369428	172809361	172809546
ENSE00001479632	172229656	172229764
ENSE00002044498	173039933	173041559
ENSE00002064652	171813404	171813990
ENSE00002470368	172882790	172882907
ENSE00003466539	172311614	172311752
ENSE00003552961	172348523	172348689
ENSE00003635553	171814412	171814718

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 80.75.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1643 / max 8.0571, expressed in 86 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50598	0.1643	86

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.81	gold quality
prefrontal cortex	UBERON:0000451	72.59	gold quality
cortical plate	UBERON:0005343	70.18	gold quality
nucleus accumbens	UBERON:0001882	69.28	gold quality
anterior cingulate cortex	UBERON:0009835	68.99	gold quality
Brodmann (1909) area 9	UBERON:0013540	67.49	gold quality
spleen	UBERON:0002106	66.40	gold quality
buccal mucosa cell	CL:0002336	66.18	gold quality
right frontal lobe	UBERON:0002810	65.45	gold quality
neocortex	UBERON:0001950	64.98	gold quality
ventricular zone	UBERON:0003053	64.97	gold quality
hypothalamus	UBERON:0001898	64.93	gold quality
frontal cortex	UBERON:0001870	64.63	gold quality
amygdala	UBERON:0001876	64.49	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	64.07	gold quality
putamen	UBERON:0001874	64.02	gold quality
substantia nigra	UBERON:0002038	63.94	gold quality
caudate nucleus	UBERON:0001873	63.88	gold quality
midbrain	UBERON:0001891	61.99	gold quality
cerebral cortex	UBERON:0000956	60.49	gold quality
descending thoracic aorta	UBERON:0002345	60.08	gold quality
left testis	UBERON:0004533	58.74	gold quality
forebrain	UBERON:0001890	58.65	gold quality
testis	UBERON:0000473	58.55	gold quality
brain	UBERON:0000955	57.90	gold quality
thoracic aorta	UBERON:0001515	57.37	gold quality
right testis	UBERON:0004534	57.26	gold quality
ascending aorta	UBERON:0001496	57.17	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	55.93	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	3123.67
E-HCAD-25	yes	2749.26
E-ANND-3	yes	5.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting GALNTL6, 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-4282	99.99	75.36	6408
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-1295B-5P	99.03	67.50	810
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-3146	98.85	66.77	601
HSA-MIR-942-3P	98.81	69.04	876
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-761	98.71	68.07	2051

Literature-anchored findings (GeneRIF, showing 2)

• a novel member of the human ppGalNAc-T family, ppGalNAc-T20, which has high homology with human ppGalNAc-T10 was identified. (PMID:20977886)
• The GALNTL6 Gene rs558129 Polymorphism Is Associated With Power Performance. (PMID:33105351)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	galntl6	ENSDARG00000040048
mus_musculus	Galntl6	ENSMUSG00000096914
rattus_norvegicus	Galntl6	ENSRNOG00000067282
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), GALNT6 (ENSG00000139629), GALNT1 (ENSG00000141429), GALNT2 (ENSG00000143641), GALNT13 (ENSG00000144278), GALNT14 (ENSG00000158089), GALNT10 (ENSG00000164574), GALNT11 (ENSG00000178234), GALNT9 (ENSG00000182870), GALNT17 (ENSG00000185274), GALNT4 (ENSG00000257594)

Protein

Protein identifiers

Polypeptide N-acetylgalactosaminyltransferase-like 6 — Q49A17 (reviewed: Q49A17)

Alternative names: Polypeptide GalNAc transferase 17, Protein-UDP acetylgalactosaminyltransferase 17, Putative polypeptide N-acetylgalactosaminyltransferase 17, UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 17

All UniProt accessions (3): Q49A17, D6RCP4, E5D8G0

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.

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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q49A17-1	1	yes
Q49A17-2	2

RefSeq proteins (1): NP_001030017* (*=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 (27 total): binding site 9, disulfide bond 5, sequence conflict 3, topological domain 2, glycosylation site 2, region of interest 2, chain 1, transmembrane region 1, splice variant 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q49A17-F1	91.03	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.

Ligand- & substrate-binding residues (9): 233; 234; 337; 365; 368; 373; 180; 209; 232

Disulfide bonds (5): 130–360, 351–427, 466–483, 518–533, 558–573

Glycosylation sites (2): 141, 588

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 77 (showing top): chr4q34, CACCAGC_MIR138, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, CATTTCA_MIR203, MYOD_01, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, chr7q11, DOUGLAS_BMI1_TARGETS_UP, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GTCAGGA_MIR378, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION_VIA_N_ACETYL_GALACTOSAMINE, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, GRYDER_PAX3FOXO1_TOP_ENHANCERS, YGCGYRCGC_UNKNOWN

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 (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
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

732 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GALNTL6	FAM162B	Q5T6X4	492
GALNTL6	AKR1E2	Q96JD6	479
GALNTL6	ZPLD1	Q8TCW7	472
GALNTL6	HS6ST3	Q8IZP7	449
GALNTL6	SORCS1	Q8WY21	422
GALNTL6	ANO2	Q9NQ90	418
GALNTL6	ADAM22	Q9P0K1	400
GALNTL6	IFRD2	Q12894	391
GALNTL6	INPP4B	O15327	389
GALNTL6	PLCH1	Q4KWH8	384
GALNTL6	CALHM3	Q86XJ0	382
GALNTL6	ARHGEF38	Q9NXL2	380
GALNTL6	SLC66A1LP	A1A4F0	377
GALNTL6	RIOK2	Q9BVS4	364
GALNTL6	OSBPL9	Q96SU4	363

IntAct

0 interactions, top by confidence:

BioGRID (2): GALNTL6 (Affinity Capture-MS), GALNTL6 (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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	141
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

5000 predictions. Top by Δscore:

Variant	Effect	Δscore
4:171813971:G:GT	donor_gain	1.0000
4:171814580:A:AG	acceptor_gain	1.0000
4:171816118:GATTT:G	donor_gain	1.0000
4:171822194:TTAAA:T	donor_gain	1.0000
4:172170047:G:GT	donor_gain	1.0000
4:172311608:T:TA	acceptor_gain	1.0000
4:172311612:A:AG	acceptor_gain	1.0000
4:172311612:AGG:A	acceptor_gain	1.0000
4:172311613:G:GG	acceptor_gain	1.0000
4:172311613:GGG:G	acceptor_gain	1.0000
4:172311748:GCTAA:G	donor_gain	1.0000
4:172311749:C:G	donor_gain	1.0000
4:172311750:TAA:T	donor_gain	1.0000
4:172311751:AAGT:A	donor_loss	1.0000
4:172311753:G:GG	donor_gain	1.0000
4:172311753:GTGA:G	donor_loss	1.0000
4:172311754:TGA:T	donor_loss	1.0000
4:172311755:GAG:G	donor_loss	1.0000
4:172311756:AGTA:A	donor_loss	1.0000
4:171814577:T:A	acceptor_gain	0.9900
4:171814580:AAT:A	acceptor_gain	0.9900
4:171814581:A:G	acceptor_gain	0.9900
4:171815330:G:GG	donor_gain	0.9900
4:171816185:A:T	donor_gain	0.9900
4:171822194:T:G	donor_gain	0.9900
4:171863214:A:AG	donor_gain	0.9900
4:171937055:G:GG	donor_gain	0.9900
4:172041223:A:T	donor_gain	0.9900
4:172092146:A:T	donor_gain	0.9900
4:172228773:A:G	donor_gain	0.9900

AlphaMissense

4000 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:172311686:G:A	G107D	1.000
4:172311688:T:C	F108L	1.000
4:172311689:T:C	F108S	1.000
4:172311690:T:A	F108L	1.000
4:172311690:T:G	F108L	1.000
4:172311703:A:C	S113R	1.000
4:172311705:C:A	S113R	1.000
4:172311705:C:G	S113R	1.000
4:172311725:G:T	R120M	1.000
4:172348674:G:C	D180H	1.000
4:172809438:G:A	G211R	1.000
4:172809438:G:C	G211R	1.000
4:172809439:G:A	G211E	1.000
4:172809442:T:A	L212H	1.000
4:172809442:T:C	L212P	1.000
4:172809453:C:A	R216S	1.000
4:172809502:A:C	D232A	1.000
4:172809502:A:T	D232V	1.000
4:172809507:C:G	H234D	1.000
4:172809512:C:G	C235W	1.000
4:172809528:T:A	W241R	1.000
4:172809528:T:C	W241R	1.000
4:172813641:G:A	G281R	1.000
4:172813641:G:C	G281R	1.000
4:172813642:G:A	G281E	1.000
4:172813653:T:A	W285R	1.000
4:172813653:T:C	W285R	1.000
4:172813655:G:C	W285C	1.000
4:172813655:G:T	W285C	1.000
4:172813670:A:C	K290N	1.000

dbSNP variants (sampled 300 via entrez): RS10000008 (4:171855053 C>T), RS1000002832 (4:172299345 G>C), RS1000005455 (4:172526054 G>A), RS1000015414 (4:172079707 T>G), RS1000019123 (4:172519995 TA>T), RS1000020200 (4:172479600 G>A,C), RS1000021658 (4:172217991 C>G,T), RS1000021885 (4:172811317 A>G), RS1000023949 (4:172166813 C>T), RS1000024714 (4:172853504 C>T), RS1000026215 (4:172470804 G>A,C), RS1000029249 (4:171897148 A>G), RS1000030842 (4:172941519 T>C), RS1000031056 (4:172123745 C>T), RS1000037139 (4:172834198 G>A,C)

Disease associations

OMIM: gene MIM:615138 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003542_115	Night sleep phenotypes	6.000000e-06
GCST006088_21	Familial squamous cell lung carcinoma	3.000000e-06
GCST006088_50	Familial squamous cell lung carcinoma	5.000000e-06
GCST007327_187	Smoking status (ever vs never smokers)	6.000000e-12
GCST008892_5	Working memory	3.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006953	family history of lung cancer
EFO:0004318	smoking behavior
EFO:0004335	short-term memory

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
methyleugenol	decreases expression	1
propionaldehyde	decreases expression	1
sulforaphane	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
pentanal	decreases expression	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
licochalcone B	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Aldehydes	decreases expression	1
Arsenic	affects methylation	1
Copper	affects cotreatment, decreases expression	1
Methapyrilene	increases methylation	1
Thiram	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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