GALNT7

Summary

GALNT7 (polypeptide N-acetylgalactosaminyltransferase 7, HGNC:4129) is a protein-coding gene on chromosome 4q34.1, encoding N-acetylgalactosaminyltransferase 7 (Q86SF2). Glycopeptide transferase involved in O-linked oligosaccharide biosynthesis, which catalyzes the transfer of an N-acetyl-D-galactosamine residue to an already glycosylated peptide.

This gene encodes GalNAc transferase 7, a member of the GalNAc-transferase family. The enzyme encoded by this gene controls the initiation step of mucin-type O-linked protein glycosylation and transfer of N-acetylgalactosamine to serine and threonine amino acid residues. This enzyme is a type II transmembrane protein and shares common sequence motifs with other family members. Unlike other family members, this enzyme shows exclusive specificity for partially GalNAc-glycosylated acceptor substrates and shows no activity with non-glycosylated peptides. This protein may function as a follow-up enzyme in the initiation step of O-glycosylation.

Source: NCBI Gene 51809 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 82 total — 1 likely-pathogenic
• MANE Select transcript: NM_017423

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4129
Approved symbol	GALNT7
Name	polypeptide N-acetylgalactosaminyltransferase 7
Location	4q34.1
Locus type	gene with protein product
Status	Approved
Aliases	GALNAC-T7
Ensembl gene	ENSG00000109586
Ensembl biotype	protein_coding
OMIM	605005
Entrez	51809

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000265000, ENST00000502407, ENST00000503213, ENST00000505308, ENST00000506317, ENST00000512285, ENST00000515862, ENST00000857290

RefSeq mRNA: 4 — MANE Select: NM_017423 NM_001375599, NM_001375600, NM_001375601, NM_017423

CCDS: CCDS3815, CCDS93669

Canonical transcript exons

ENST00000265000 — 12 exons

Exon	Start	End
ENSE00000741043	173247980	173248440
ENSE00001081452	173321580	173323967
ENSE00001081453	173295396	173295526
ENSE00001081454	173298115	173298297
ENSE00001081456	173295764	173295843
ENSE00002038034	173168811	173168961
ENSE00002492018	173317634	173317732
ENSE00002519690	173313958	173314176
ENSE00003479579	173303996	173304118
ENSE00003488274	173292108	173292274
ENSE00003488999	173302047	173302164
ENSE00003578446	173318431	173318559

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 98.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.9500 / max 210.1311, expressed in 1768 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50613	8.1745	1689
50612	4.3447	1522
50614	0.6810	365
50609	0.5281	270
50611	0.1918	48
50610	0.0299	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of sigmoid colon	UBERON:0004993	98.65	gold quality
colonic mucosa	UBERON:0000317	98.34	gold quality
pylorus	UBERON:0001166	97.04	gold quality
jejunal mucosa	UBERON:0000399	96.54	gold quality
rectum	UBERON:0001052	96.00	gold quality
duodenum	UBERON:0002114	94.95	gold quality
palpebral conjunctiva	UBERON:0001812	94.67	gold quality
oral cavity	UBERON:0000167	94.38	gold quality
ileal mucosa	UBERON:0000331	94.38	gold quality
bronchial epithelial cell	CL:0002328	94.06	gold quality
cerebellar vermis	UBERON:0004720	94.01	gold quality
nasal cavity epithelium	UBERON:0005384	93.40	gold quality
epithelium of bronchus	UBERON:0002031	93.27	gold quality
bronchus	UBERON:0002185	93.27	gold quality
pigmented layer of retina	UBERON:0001782	93.11	gold quality
retina	UBERON:0000966	93.09	gold quality
urethra	UBERON:0000057	92.93	gold quality
cardia of stomach	UBERON:0001162	92.90	gold quality
thymus	UBERON:0002370	91.77	gold quality
esophagus squamous epithelium	UBERON:0006920	91.60	gold quality
endometrium	UBERON:0001295	91.20	gold quality
cerebellum	UBERON:0002037	90.97	gold quality
trachea	UBERON:0003126	90.94	gold quality
cerebellar cortex	UBERON:0002129	90.82	gold quality
cerebellar hemisphere	UBERON:0002245	90.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.78	gold quality
corpus callosum	UBERON:0002336	90.71	gold quality
pharyngeal mucosa	UBERON:0000355	90.67	gold quality
epithelium of esophagus	UBERON:0001976	90.51	gold quality
endothelial cell	CL:0000115	90.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.33
E-GEOD-100618	no	568.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

197 targeting GALNT7, 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-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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-27A-3P	99.98	72.13	2955

Literature-anchored findings (GeneRIF, showing 14)

• MicroRNA miR-378 regulates nephronectin expression modulating osteoblast differentiation by targeting GalNT-7 (PMID:19844573)
• Ectopic expression of miR-30b/30d promoted the metastatic behavior of melanoma cells by directly targeting the GalNAc transferase GALNT7. (PMID:21741600)
• miR-214 is a new regulator of GALNT7, and both miR-214 and GALNT7 play important roles in the pathogenesis of cervical cancer (PMID:22399294)
• The study of miR-34a, miR-34c and its novel target, GALNT7, may serve as novel potential makers for laryngeal squamous cell carcinoma therapy. (PMID:24482044)
• GALNT7 and CDK16 were confirmed to be the direct targets of miR-494. These results suggested that miR-494 play an inhibitory role in the tumorigenesis of NPC (PMID:25809707)
• miR-494 and GALNT7 play oncogenic roles in nasopharyngeal carcinoma. (PMID:26503214)
• High expression of GALNT7 promotes migration and invasion and lymph node metastasis in esophageal squamous cell carcinoma. (PMID:27619677)
• Results indicated that SNHG7 facilitated the proliferation and metastasis as a competing endogenous RNA to regulate GALNT7 expression by sponging miR-34a in CRC cell lines. (PMID:29970122)
• crystallographic analysis of GalNAc-T7, a GalNAc-T capable of glycosylating consecutive sites, and of its complex with the donor substrate UDP-GalNAc (PMID:30685086)
• Long non-coding RNA TP73-AS1 contributes to glioma tumorigenesis by sponging the miR-103a/GALNT7 pathway. (PMID:32416102)
• MiR-30c facilitates natural killer cell cytotoxicity to lung cancer through targeting GALNT7. (PMID:36040682)
• Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth. (PMID:36725887)
• SPDEF enhances cancer stem cell-like properties and tumorigenesis through directly promoting GALNT7 transcription in luminal breast cancer. (PMID:37633945)
• The expression of O-linked glycosyltransferase GALNT7 in breast cancer is dependent on estrogen-, progesterone-, and HER2-receptor status, with prognostic implications. (PMID:37947928)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	galnt7	ENSDARG00000057303
mus_musculus	Galnt7	ENSMUSG00000031608
rattus_norvegicus	Galnt7	ENSRNOG00000012037
drosophila_melanogaster	Pgant5	FBGN0031681
drosophila_melanogaster	Pgant9	FBGN0050463
caenorhabditis_elegans		WBGENE00001628
caenorhabditis_elegans		WBGENE00001630

Paralogs (19): GALNT16 (ENSG00000100626), GALNTL5 (ENSG00000106648), GALNT18 (ENSG00000110328), GALNT3 (ENSG00000115339), GALNT12 (ENSG00000119514), GALNT8 (ENSG00000130035), GALNT15 (ENSG00000131386), GALNT5 (ENSG00000136542), 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

N-acetylgalactosaminyltransferase 7 — Q86SF2 (reviewed: Q86SF2)

Alternative names: Polypeptide GalNAc transferase 7, Protein-UDP acetylgalactosaminyltransferase 7, UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 7

All UniProt accessions (4): Q86SF2, E9PBY3, H0YAH3, H0YAK0

UniProt curated annotations — full annotation on UniProt →

Function. Glycopeptide transferase involved in O-linked oligosaccharide biosynthesis, which catalyzes the transfer of an N-acetyl-D-galactosamine residue to an already glycosylated peptide. In contrast to other proteins of the family, it does not act as a peptide transferase that transfers GalNAc onto serine or threonine residue on the protein receptor, but instead requires the prior addition of a GalNAc on a peptide before adding additional GalNAc moieties. Some peptide transferase activity is however not excluded, considering that its appropriate peptide substrate may remain unidentified.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Widely expressed. Expressed in uterus, retina, kidney, small intestine, omentum, stomach and CNS.

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 (4): NP_001362528, NP_001362529, NP_001362530, NP_059119* (*=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 (77 total): strand 28, helix 22, binding site 7, disulfide bond 5, sequence conflict 4, turn 3, region of interest 3, topological domain 2, chain 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6IWR	X-RAY DIFFRACTION	2.6
6IWQ	X-RAY DIFFRACTION	2.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86SF2-F1	88.05	0.79

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): 301; 303; 412; 440; 443; 247; 277

Disulfide bonds (5): 197–435, 426–507, 545–562, 585–600, 625–640

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 225 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, ROVERSI_GLIOMA_COPY_NUMBER_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, DITTMER_PTHLH_TARGETS_UP, chr4q34, CTATGCA_MIR153, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, ONKEN_UVEAL_MELANOMA_UP, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, MCBRYAN_PUBERTAL_BREAST_5_6WK_UP, GARY_CD5_TARGETS_DN, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP

GO Biological Process (4): carbohydrate metabolic process (GO:0005975), 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 (4): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), membrane (GO:0016020), extracellular exosome (GO:0070062)

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
primary 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
extracellular vesicle	1

Protein interactions and networks

STRING

388 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GALNT7	ST3GAL3	Q11203	428
GALNT7	ZNF668	Q96K58	378
GALNT7	C1GALT1	Q9NS00	370
GALNT7	SEC23IP	Q9Y6Y8	369
GALNT7	ST6GALNAC6	Q969X2	356
GALNT7	SDAD1	Q9NVU7	322
GALNT7	DOLPP1	Q86YN1	316
GALNT7	MTAP	Q13126	313
GALNT7	USO1	O60763	305
GALNT7	CEP43	O95684	303
GALNT7	SMPDL3A	Q92484	293
GALNT7	ABCB9	Q9NP78	285
GALNT7	ST6GAL2	Q96JF0	281
GALNT7	ST3GAL2	Q16842	279
GALNT7	LMAN2	Q12907	275
GALNT7	DIS3	Q9Y2L1	275

IntAct

87 interactions, top by confidence:

A	B	Type	Score
MME	TMEM223	psi-mi:“MI:0914”(association)	0.530
ANTXR1	POTEF	psi-mi:“MI:0914”(association)	0.530
DEFA5	NUDT19	psi-mi:“MI:0914”(association)	0.530
REEP5	SCAMP1	psi-mi:“MI:0914”(association)	0.530
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
REEP5	PLSCR1	psi-mi:“MI:0914”(association)	0.530
CMA1	MANBA	psi-mi:“MI:0914”(association)	0.530
DNAJC3	DEDD	psi-mi:“MI:0914”(association)	0.530
GPIHBP1	ADAM10	psi-mi:“MI:0914”(association)	0.530
GALNT7	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
MAPK6	GALNT7	psi-mi:“MI:0915”(physical association)	0.370
COL5A1	GALNT7	psi-mi:“MI:0915”(physical association)	0.370
DKKL1	VWA8	psi-mi:“MI:0914”(association)	0.350
ADPGK	TOR1B	psi-mi:“MI:0914”(association)	0.350
MPPE1	ADAM10	psi-mi:“MI:0914”(association)	0.350
NCEH1	C1QL1	psi-mi:“MI:0914”(association)	0.350
B3GNT2	NDUFA10	psi-mi:“MI:0914”(association)	0.350
GALNT7	GAA	psi-mi:“MI:0914”(association)	0.350
PLTP	CANX	psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
HLA-DQA1	TMEM223	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
TCTN2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
KLRC1	METTL15	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
CEACAM8	PRRT4	psi-mi:“MI:0914”(association)	0.350

BioGRID (101): GALNT7 (Affinity Capture-MS), GALNT7 (Affinity Capture-MS), GALNT7 (Affinity Capture-MS), GALNT7 (Affinity Capture-MS), GALNT7 (Affinity Capture-MS), GALNT7 (Affinity Capture-MS), GALNT7 (Affinity Capture-MS), GALNT7 (Affinity Capture-MS), GALNT7 (Affinity Capture-MS), GALNT7 (Affinity Capture-MS), GALNT7 (Affinity Capture-MS), SLC9A1 (Affinity Capture-MS), GALNT7 (Affinity Capture-MS), GALNT7 (Affinity Capture-MS), GALNT7 (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 131 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	42.4×	4e-07
R-HSA-425366	9	19.2×	2e-07
SLC transporter disorders	6	14.4×	2e-04
Disorders of transmembrane transporters	6	9.8×	1e-03
SLC-mediated transmembrane transport	14	9.8×	5e-08
Transport of small molecules	15	4.4×	7e-05
Neutrophil degranulation	15	4.1×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	10	59.5×	3e-13
intracellular zinc ion homeostasis	9	36.7×	7e-10
amino acid transport	5	13.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	60
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4075890	GRCh37/hg19 4q34.1(chr4:174151474-174626932)x1	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

4345 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:173292259:G:C	D247H	1.000
4:173295476:G:C	G279R	1.000
4:173295501:G:A	G287D	1.000
4:173295777:T:C	L300P	1.000
4:173295780:A:T	D301V	1.000
4:173298215:T:A	W356R	1.000
4:173298215:T:C	W356R	1.000
4:173298221:T:A	W358R	1.000
4:173298221:T:C	W358R	1.000
4:173298223:G:C	W358C	1.000
4:173298223:G:T	W358C	1.000
4:173298233:T:A	W362R	1.000
4:173298233:T:C	W362R	1.000
4:173298235:G:C	W362C	1.000
4:173298235:G:T	W362C	1.000
4:173302064:G:A	G389E	1.000
4:173302124:T:C	L409P	1.000
4:173302132:T:A	W412R	1.000
4:173302132:T:C	W412R	1.000
4:173302134:G:C	W412C	1.000
4:173302134:G:T	W412C	1.000
4:173302142:A:T	E415V	1.000
4:173302146:C:A	N416K	1.000
4:173302146:C:G	N416K	1.000
4:173302164:G:C	K422N	1.000
4:173302164:G:T	K422N	1.000
4:173304047:C:G	H440D	1.000
4:173313960:T:A	N464K	1.000
4:173313960:T:G	N464K	1.000
4:173313982:T:A	W472R	1.000

dbSNP variants (sampled 300 via entrez): RS1000041974 (4:173210741 C>T), RS1000071281 (4:173218441 C>T), RS1000077514 (4:173299464 G>A), RS1000087014 (4:173306509 T>C), RS1000104115 (4:173173603 C>T), RS1000105653 (4:173313748 T>C), RS10001613 (4:173210995 G>A), RS1000162464 (4:173262275 A>C), RS1000182395 (4:173217530 A>C), RS1000196829 (4:173256113 G>A), RS1000262766 (4:173211124 A>G), RS1000269838 (4:173203693 T>G), RS1000297747 (4:173167028 G>A,C), RS1000310069 (4:173305995 T>C), RS1000347525 (4:173312419 A>G)

Disease associations

OMIM: gene MIM:605005 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002592_18	Neuritic plaque	6.000000e-09
GCST009391_481	Metabolite levels	5.000000e-06
GCST009391_652	Metabolite levels	9.000000e-06
GCST010002_20	Refractive error	2.000000e-15

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006798	neuritic plaque measurement
EFO:0010389	phosphatidylcholine 40:6 measurement
EFO:0007745	lactate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, affects cotreatment, increases abundance	4
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, increases methylation	4
Resveratrol	affects cotreatment, decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Arsenic	increases abundance, affects methylation, affects cotreatment, decreases expression	2
Benzo(a)pyrene	increases expression	2
Smoke	increases expression, decreases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Aflatoxin B1	affects expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
sotorasib	affects cotreatment, increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
LDN 193189	decreases expression, affects cotreatment	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Cadmium	increases expression	1
Carbamazepine	affects expression	1
Cisplatin	affects response to substance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery