GALNT12

Summary

GALNT12 (polypeptide N-acetylgalactosaminyltransferase 12, HGNC:19877) is a protein-coding gene on chromosome 9q22.33, encoding Polypeptide N-acetylgalactosaminyltransferase 12 (Q8IXK2). 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 a family of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases, which catalyze the transfer of N-acetylgalactosamine (GalNAc) from UDP-GalNAc to a serine or threonine residue on a polypeptide acceptor in the initial step of O-linked protein glycosylation. Mutations in this gene are associated with an increased susceptibility to colorectal cancer.

Source: NCBI Gene 79695 — RefSeq curated summary.

At a glance

• Gene–disease (curated): colorectal cancer, susceptibility to, 1 (Limited, ClinGen)
• GWAS associations: 11
• Clinical variants (ClinVar): 1,734 total
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_024642

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19877
Approved symbol	GALNT12
Name	polypeptide N-acetylgalactosaminyltransferase 12
Location	9q22.33
Locus type	gene with protein product
Status	Approved
Aliases	GalNAc-T12
Ensembl gene	ENSG00000119514
Ensembl biotype	protein_coding
OMIM	610290
Entrez	79695

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000375011, ENST00000470473, ENST00000610463, ENST00000615204, ENST00000931577, ENST00000931578, ENST00000931579, ENST00000931580, ENST00000969912, ENST00000969913

RefSeq mRNA: 1 — MANE Select: NM_024642 NM_024642

CCDS: CCDS6737

Canonical transcript exons

ENST00000375011 — 10 exons

Exon	Start	End
ENSE00000715529	98836972	98837148
ENSE00000805699	98835249	98835366
ENSE00000805700	98840002	98840133
ENSE00000805701	98844096	98844209
ENSE00000805702	98845977	98846123
ENSE00001022859	98831772	98831957
ENSE00001022862	98826752	98826941
ENSE00001022867	98823256	98823425
ENSE00001465439	98848952	98850081
ENSE00001465464	98807670	98808069

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 98.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.8728 / max 192.3998, expressed in 1319 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97611	6.9508	1132
97610	1.8442	826
97613	0.0778	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	98.71	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.50	gold quality
corpus epididymis	UBERON:0004359	97.26	gold quality
colonic mucosa	UBERON:0000317	97.19	gold quality
esophagus squamous epithelium	UBERON:0006920	97.07	gold quality
rectum	UBERON:0001052	96.08	gold quality
epithelium of esophagus	UBERON:0001976	95.54	gold quality
nasal cavity epithelium	UBERON:0005384	95.42	gold quality
transverse colon	UBERON:0001157	93.04	gold quality
mucosa of transverse colon	UBERON:0004991	92.78	gold quality
nasal cavity mucosa	UBERON:0001826	92.66	gold quality
bronchial epithelial cell	CL:0002328	92.17	gold quality
large intestine	UBERON:0000059	92.04	gold quality
colon	UBERON:0001155	91.87	gold quality
ileal mucosa	UBERON:0000331	91.68	gold quality
jejunal mucosa	UBERON:0000399	91.23	gold quality
body of stomach	UBERON:0001161	91.14	gold quality
oral cavity	UBERON:0000167	91.01	gold quality
intestine	UBERON:0000160	90.92	gold quality
epithelium of bronchus	UBERON:0002031	90.80	gold quality
bronchus	UBERON:0002185	90.60	gold quality
cerebellar hemisphere	UBERON:0002245	90.52	gold quality
cerebellar cortex	UBERON:0002129	90.34	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.09	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.03	gold quality
duodenum	UBERON:0002114	89.98	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.97	gold quality
stomach	UBERON:0000945	89.70	gold quality
germinal epithelium of ovary	UBERON:0001304	89.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting GALNT12, 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-513A-5P	100.00	69.77	2465
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-5197-5P	99.64	69.08	1494

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 10)

• cloning and characterization (PMID:12135769)
• The expression of pp-GalNAc-T12 seems to be a negative marker especially of metastatic gastric and colorectal cancer (PMID:15557789)
• inactivating GALNT12 mutations were identified as acquired somatic mutations in a set of 30 microsatellite stable colon tumors. (PMID:19617566)
• Inherited deleterious variants in GALNT12 are associated with CRC susceptibility. (PMID:22461326)
• we integrated different computational tools to perform the in silico analysis of clinically significant mutations (nsSNPs/single amino acid change) at both functional and structural levels, found in human GALNT3, GALNT8, GALNT12, and GALNT13 genes. (PMID:24038392)
• Results rule out GALNT12 as a major high familial colorectal cancer susceptibility gene. Additional studies are required to provide further evidence about its role as a moderate/low susceptibility gene in familial aggregation of cancer. (PMID:24115450)
• LOH analyses, glycosylation pattern tests and case-control studies, our results did not support the role of c.907G>A, p.(D303N) as a high-penetrance risk allele for polyposis CRC (PMID:29095867)
• The findings provide strong, independent evidence for the association of GALNT12 defects with CRC-susceptibility; underscoring implications for glycosylation pathway defects in CRC. (PMID:29749045)
• Interaction between G ALNT12 and C1GALT1 Associates with Galactose-Deficient IgA1 and IgA Nephropathy. (PMID:33593824)
• GALNT12 is associated with the malignancy of glioma and promotes glioblastoma multiforme in vitro by activating Akt signaling. (PMID:35461073)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	galnt12	ENSDARG00000055490
mus_musculus	Galnt12	ENSMUSG00000039774
rattus_norvegicus	Galnt12	ENSRNOG00000008099
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), 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

Polypeptide N-acetylgalactosaminyltransferase 12 — Q8IXK2 (reviewed: Q8IXK2)

Alternative names: Polypeptide GalNAc transferase 12, Protein-UDP acetylgalactosaminyltransferase 12, UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 12

All UniProt accessions (2): A0A087WT76, Q8IXK2

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 non-glycosylated peptides such as Muc5AC, Muc1a and EA2, and no detectable activity with Muc2 and Muc7. Displays enzymatic activity toward the Gal-NAc-Muc5AC glycopeptide, but no detectable activity to mono-GalNAc-glycosylated Muc1a, Muc2, Muc7 and EA2. May play an important role in the initial step of mucin-type oligosaccharide biosynthesis in digestive organs.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Widely expressed at different levels of expression. Highly expressed in digestive organs such as small intestine, stomach, pancreas and colon. Expressed at intermediate level in testis, thyroid gland and spleen. Weakly expressed in whole brain, cerebral cortex, cerebellum, fetal brain, bone marrow, thymus, leukocytes, heart, skeletal muscle, liver, lung, esophagus, kidney, adrenal gland, mammary gland, uterus, placenta, ovary and prostate.

Disease relevance. Colorectal cancer 1 (CRCS1) [MIM:608812] A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Disease susceptibility is associated with variants affecting the gene represented in this entry. The role of GALNT12 in colon cancer susceptibility is however subject to discussion: studies on 103 probants with colorectal cancer 1 (CRCS1) suggest that it does not act as a major contributor of CRCS1.

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?
Q8IXK2-1	1	yes
Q8IXK2-2	2

RefSeq proteins (1): NP_078918* (*=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 (87 total): strand 26, helix 21, sequence variant 14, binding site 7, disulfide bond 5, turn 5, region of interest 3, topological domain 2, chain 1, transmembrane region 1, splice variant 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6PXU	X-RAY DIFFRACTION	2.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXK2-F1	93.84	0.90

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): 228; 230; 335; 363; 371; 176; 205

Disulfide bonds (5): 125–358, 349–422, 458–479, 506–521, 547–566

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5083636	Defective GALNT12 causes CRCS1
R-HSA-913709	O-linked glycosylation of mucins

MSigDB gene sets: 145 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, AML_Q6, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, WAGNER_APO2_SENSITIVITY, RIGGI_EWING_SARCOMA_PROGENITOR_DN, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, OCT1_06, chr9q22, GAUSSMANN_MLL_AF4_FUSION_TARGETS_B_UP, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION_VIA_N_ACETYL_GALACTOSAMINE, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, DURCHDEWALD_SKIN_CARCINOGENESIS_DN

GO Biological Process (3): protein O-linked glycosylation (GO:0006493), protein O-linked glycosylation via N-acetylgalactosamine (GO:0016266), obsolete protein glycosylation (GO:0006486)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Diseases associated with O-glycosylation of proteins	1
O-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	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
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

680 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GALNT12	POLD1	P28340	756
GALNT12	MUTYH	Q9UIF7	736
GALNT12	MLH3	P49751	666
GALNT12	GREM1	O60565	663
GALNT12	GCNT1	Q02742	649
GALNT12	PMS2	P54278	648
GALNT12	B4GALNT1	Q00973	616
GALNT12	PMS1	P54277	596
GALNT12	MSH6	P52701	590
GALNT12	MUC7	Q8TAX7	590
GALNT12	AXIN2	Q9Y2T1	559
GALNT12	C1GALT1C1	Q96EU7	555
GALNT12	MUC5AC	P98088	536
GALNT12	MUC2	Q02817	522
GALNT12	GCNT3	O95395	514

IntAct

113 interactions, top by confidence:

A	B	Type	Score
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
PTPRA	LGALS1	psi-mi:“MI:0914”(association)	0.640
HPX	GALNT12	psi-mi:“MI:0915”(physical association)	0.640
MGAT4C	GXYLT2	psi-mi:“MI:0914”(association)	0.530
ODAPH	TCAF2	psi-mi:“MI:0914”(association)	0.530
LAMP3	METTL15	psi-mi:“MI:0914”(association)	0.530
CD1B	TOR1B	psi-mi:“MI:0914”(association)	0.530
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
ADAM33	LRP5	psi-mi:“MI:0914”(association)	0.530
FUT3	C1QL1	psi-mi:“MI:0914”(association)	0.530
PTPRA	LGALS8	psi-mi:“MI:0914”(association)	0.530
GALNT12	RAB3GAP1	psi-mi:“MI:0915”(physical association)	0.400
GALNT12	BMPR1A	psi-mi:“MI:0915”(physical association)	0.370
GALNT12	BUB1	psi-mi:“MI:0915”(physical association)	0.370
CDH1	GALNT12	psi-mi:“MI:0915”(physical association)	0.370
GALNT12	CDKN2A	psi-mi:“MI:0915”(physical association)	0.370
FBXW7	GALNT12	psi-mi:“MI:0915”(physical association)	0.370
MLH3	GALNT12	psi-mi:“MI:0915”(physical association)	0.370
GALNT12	MSH2	psi-mi:“MI:0915”(physical association)	0.370
PIK3CA	GALNT12	psi-mi:“MI:0915”(physical association)	0.370
PMS2	GALNT12	psi-mi:“MI:0915”(physical association)	0.370
RB1	GALNT12	psi-mi:“MI:0915”(physical association)	0.370
GALNT12	SRC	psi-mi:“MI:0915”(physical association)	0.370
PIANP	TCAF2	psi-mi:“MI:0914”(association)	0.350
HLA-E	RTL8C	psi-mi:“MI:0914”(association)	0.350

BioGRID (118): GALNT12 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), GALNT12 (Affinity Capture-MS), GALNT12 (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: 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 146 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.

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	6	31.7×	1e-05
protein O-linked glycosylation via N-acetylgalactosamine	6	19.5×	2e-04
intracellular zinc ion homeostasis	5	18.1×	2e-03
T cell costimulation	5	14.1×	4e-03
epidermal growth factor receptor signaling pathway	6	11.2×	3e-03
protein O-linked glycosylation	6	10.1×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1734 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1158
Likely benign	448
Benign	28

Top pathogenic / likely-pathogenic (0)

SpliceAI

2563 predictions. Top by Δscore:

Variant	Effect	Δscore
9:98808065:CCGCT:C	donor_gain	1.0000
9:98808067:GCT:G	donor_gain	1.0000
9:98808070:G:GG	donor_gain	1.0000
9:98826747:CCTA:C	acceptor_loss	1.0000
9:98826750:A:AG	acceptor_gain	1.0000
9:98826751:G:GG	acceptor_gain	1.0000
9:98826751:GA:G	acceptor_gain	1.0000
9:98826751:GAGC:G	acceptor_gain	1.0000
9:98826751:GAGCA:G	acceptor_gain	1.0000
9:98839998:TCA:T	acceptor_loss	1.0000
9:98839999:CA:C	acceptor_loss	1.0000
9:98840000:A:AG	acceptor_gain	1.0000
9:98840000:AG:A	acceptor_gain	1.0000
9:98840000:AGG:A	acceptor_loss	1.0000
9:98840001:G:A	acceptor_loss	1.0000
9:98840001:G:GA	acceptor_gain	1.0000
9:98840001:GG:G	acceptor_gain	1.0000
9:98840001:GGA:G	acceptor_gain	1.0000
9:98840001:GGAA:G	acceptor_gain	1.0000
9:98840129:GGATG:G	donor_gain	1.0000
9:98840130:GATG:G	donor_gain	1.0000
9:98840130:GATGG:G	donor_gain	1.0000
9:98840134:GT:G	donor_loss	1.0000
9:98840135:T:A	donor_loss	1.0000
9:98840136:G:GT	donor_loss	1.0000
9:98844094:A:AG	acceptor_gain	1.0000
9:98844095:G:GT	acceptor_gain	1.0000
9:98844206:TCAG:T	donor_loss	1.0000
9:98844207:CAGG:C	donor_loss	1.0000
9:98844209:GGTA:G	donor_loss	1.0000

AlphaMissense

3785 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:98826893:A:T	D228V	1.000
9:98831893:T:C	F285L	1.000
9:98831895:C:A	F285L	1.000
9:98831895:C:G	F285L	1.000
9:98835334:T:A	W335R	1.000
9:98835334:T:C	W335R	1.000
9:98837023:C:G	H363D	1.000
9:98823303:T:A	V140D	0.999
9:98826853:G:T	G215W	0.999
9:98826886:T:C	F226L	0.999
9:98826888:C:A	F226L	0.999
9:98826888:C:G	F226L	0.999
9:98826890:T:C	L227P	0.999
9:98826893:A:C	D228A	0.999
9:98826894:C:A	D228E	0.999
9:98826894:C:G	D228E	0.999
9:98826902:G:A	C231Y	0.999
9:98826903:T:G	C231W	0.999
9:98826909:C:G	C233W	0.999
9:98826919:T:A	W237R	0.999
9:98826919:T:C	W237R	0.999
9:98831881:T:A	W281R	0.999
9:98831881:T:C	W281R	0.999
9:98835336:G:C	W335C	0.999
9:98835336:G:T	W335C	0.999
9:98835348:C:A	N339K	0.999
9:98835348:C:G	N339K	0.999
9:98835359:C:T	S343F	0.999
9:98837018:T:A	V361D	0.999
9:98837023:C:A	H363N	0.999

dbSNP variants (sampled 300 via entrez): RS1000002652 (9:98835042 G>C), RS1000247093 (9:98811248 A>C), RS1000254723 (9:98838584 C>T), RS1000353587 (9:98832794 A>G), RS1000363008 (9:98827780 A>G), RS1000366069 (9:98829501 A>G), RS1000383139 (9:98833043 G>A,C,T), RS1000431081 (9:98817242 A>T), RS1000436687 (9:98841408 G>T), RS1000496980 (9:98846197 T>G), RS1000532816 (9:98810073 A>C,G), RS1000635986 (9:98817587 C>T), RS1000718484 (9:98811595 G>A), RS1000945355 (9:98829168 T>C), RS1000971713 (9:98828368 A>G)

Disease associations

OMIM: gene MIM:610290 | disease phenotypes: MIM:608812, MIM:114500

GenCC curated gene-disease

Disease	Classification	Inheritance
colorectal cancer, susceptibility to, 1	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
colorectal cancer, susceptibility to, 1	Limited	AD

Mondo (5): colorectal cancer, susceptibility to, 1 (MONDO:0012132), hereditary neoplastic syndrome (MONDO:0015356), familial colorectal cancer (MONDO:0023113), breast neoplasm (MONDO:0021100), colorectal cancer (MONDO:0005575)

Orphanet (2): Inherited cancer-predisposing syndrome (Orphanet:140162), NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST007430_46	Peak expiratory flow	6.000000e-07
GCST007431_10	Lung function (FEV1/FVC)	5.000000e-13
GCST007432_88	FEV1	6.000000e-08
GCST009798_9	Asthma	2.000000e-10
GCST010396_157	Gut microbiota (bacterial taxa, hurdle binary method)	2.000000e-06
GCST010703_310	Brain morphology (MOSTest)	5.000000e-25
GCST011516_1	joint destruction in rheumatoid arthritis (rapid vs slow)	6.000000e-08
GCST011517_2	joint destruction in rheumatoid arthritis (rapid vs slow)	8.000000e-08
GCST012466_3	Autism spectrum disorder	3.000000e-06
GCST90010427_13	Left–right brain asymmetry	2.000000e-15
GCST90011884_2	Serum galactose-deficient IgA1 levels in IgA nephropathy	2.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0004314	forced expiratory volume
EFO:0007874	gut microbiome measurement
EFO:0004346	neuroimaging measurement
EFO:0005413	joint damage measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001943	Breast Neoplasms	C04.588.180; C17.800.090.500
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700

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
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	4
Valproic Acid	affects expression, decreases expression, increases expression	4
Estradiol	affects expression, increases reaction, affects cotreatment, increases expression, decreases expression	3
Cadmium Chloride	increases abundance, increases expression, decreases expression	3
Dexamethasone	decreases expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	decreases expression	2
Tretinoin	decreases expression, increases expression	2
bisphenol F	affects cotreatment, increases expression	1
TL8-506	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
trichostatin A	decreases expression	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
aflatoxin B2	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cadmium	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00092183	PHASE4	COMPLETED	An Investigational Drug for the Prevention of Chemotherapy-Induced Nausea and Vomiting (MK-0869-071)
NCT00128778	PHASE4	COMPLETED	Maintenance Treatment With Liposomal Doxorubicin (Caelyx) in Metastatic Breast Cancer Patients
NCT00302120	PHASE4	UNKNOWN	The MONET - Study: MR Mammography of Nonpalpable Breast Tumors
NCT00307606	PHASE4	UNKNOWN	Does a Single Steroid Injection Reduce the Formation of Postmastectomy Seroma
NCT00370240	PHASE4	COMPLETED	Chlorhydrate of Ropivacaine and Breast Cancer Surgery
NCT00375752	PHASE4	TERMINATED	Efficacy and Safety of Letrozole vs. Letrozole Plus Zoledronic Acid as Endocrine Therapy Before Surgery in Postmenopausal Patients With Breast Cancer
NCT00575354	PHASE4	COMPLETED	Comparison of Sevoflurane and Isoflurane Anesthesia for Benign Breast Tumor Excision
NCT00604968	PHASE4	TERMINATED	Pegylated Liposomal Doxorubicin (Caelyx(R)) as Monotherapy in Elderly Patients With Locally Advanced and/or Metastatic Breast Cancer (Study P05059)
NCT00616135	PHASE4	COMPLETED	Study of Autologous Fat Enhanced w/ Regenerative Cells Transplanted to Reconstruct Breast Deformities After Lumpectomy
NCT00649090	PHASE4	COMPLETED	A Study to Evaluate the Safety of Adjuvant Treatment With Exemestane Following Previous Treatment With Tamoxifen in Postmenopausal Women With Estrogen Sensitive Primary Breast Cancer
NCT00779285	PHASE4	TERMINATED	Safety Study of CAELYX in Patients With Metastatic Breast Cancer Previously Treated With Anthracyclines (Study P04057)(TERMINATED)
NCT01176916	PHASE4	COMPLETED	Aromasin® Interventional Study Of Early Invasive Breast Cancer Patients In China
NCT01427400	PHASE4	UNKNOWN	The Use of Botulinum Toxin A in Two-Stage Tissue Expander/ Implant Breast Reconstruction
NCT01849380	PHASE4	UNKNOWN	Neoadjuvant ECS Versus ECF in Local Advanced Breast Cancer
NCT01859936	PHASE4	COMPLETED	Will Preoperative MRI Breast in Women Under 56 Years With Breast Cancer Change Primary Treatment
NCT01948960	PHASE4	COMPLETED	Influence of Exceptional Patient Characteristics on Everolimus Exposure
NCT01961544	PHASE4	COMPLETED	Eribulin Mesylate Phase IV Clinical Trial in Korean Patients With Metastatic or Locally Advanced Breast Cancer
NCT01975064	PHASE4	COMPLETED	Cancer and Anesthesia: Survival After Radical Surgery - a Comparison Between Propofol or Sevoflurane Anesthesia
NCT02004834	PHASE4	ACTIVE_NOT_RECRUITING	Levobupivacaine and Lidocaine for Paravertebral Block Causes Greater Hemodynamic Oscillations Than Levobupivacaine
NCT02372305	PHASE4	WITHDRAWN	Comparison of FlexHD and Alloderm Outcomes in Breast Reconstructive Surgery
NCT02479347	PHASE4	COMPLETED	Wound Infections in Breast Cancer Surgery After Preoperative Skin Preparation With Chlorhexidine vs. Povidone-iodine
NCT02549677	PHASE4	COMPLETED	Epirubicin Versus Docetaxel Plus Cyclophosphamide in Lymph Node Negative, ER-positive, Her2-negative Breast Cancer
NCT02612870	PHASE4	UNKNOWN	Sienna+® Injection Time Study 4 Arms
NCT02627560	PHASE4	COMPLETED	The Effect of Topical Tranexamic Acid on Bleeding and Seroma Formation in After Undergoing Mastectomy
NCT02661932	PHASE4	COMPLETED	Fertility Preservation in Breast Cancer Patients
NCT02781259	PHASE4	UNKNOWN	Selective Lymph Node Dissection Using Fluorescent Dye in Node-positive Breast Cancer
NCT02819921	PHASE4	TERMINATED	Desvenlafaxine for Treatment of Hot Flashes in Women With Breast Cancer Taking Tamoxifen
NCT03220178	PHASE4	TERMINATED	Impact of eHealth-support on Quality of Life in Metastatic Breast Cancer Patients Treated With Palbociclib and Endocrine Therapy
NCT03583944	PHASE4	COMPLETED	A Study to Evaluate Safety, Tolerability and Efficacy of Eribulin Mesylate in Treating Adult Females With Locally Advanced or Metastatic Breast Cancer
NCT03586154	PHASE4	COMPLETED	Combined Intra-articular Shoulder Injection and Stellate Ganglion Block in Chronic Post-mastectomy Shoulder Pain
NCT04707196	PHASE4	COMPLETED	A Study of Abemaciclib in Indian Women With Advanced Breast Cancer
NCT04931615	PHASE4	COMPLETED	ARTISS a Single-centre Randomised Control Study
NCT05033769	PHASE4	UNKNOWN	Assessing ImmunoResponse Post Eribulin: Eribulin and Immunogenicity in Advanced Breast Cancer
NCT05036005	PHASE4	UNKNOWN	Neoadjuvant Ontruzant (SB3) in Patients With HER2-positive Early Breast Cancer: An Open-Label (NeoON)
NCT05452213	PHASE4	RECRUITING	Comprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients
NCT05465031	PHASE4	RECRUITING	Sacubitril/Valsartan in PriMAry preventIoN of the Cardiotoxicity of Systematic breaST canceR trEAtMent (MAINSTREAM)
NCT05949333	PHASE4	UNKNOWN	Reducing Neutropenia Incidence With Pegfilgrastim Administration on Day 3 After Chemotherapy
NCT07158164	PHASE4	RECRUITING	DPYD Pharmacogenomics and Fluoropyrimidine (FP) Dose-Adjustment
NCT07162259	PHASE4	NOT_YET_RECRUITING	Cohort Study on Sequential ADC Therapy in HR-positive/HER2-negative Advanced Breast Cancer
NCT00000611	PHASE3	COMPLETED	Women’s Health Initiative (WHI)