Gene, genetics and genetic medicines in gastroenterology: Current status and its future

Table 3 Classification of genes based on their function and their association with gastrointestinal disorders[10-16]

Genes	Function	Associated disorders
Genes involved in DNA repair and genomic stability[10]
MLH1, MSH2, MSH6, PMS2, EPCAM	Mismatch repair (MMR) system	Lynch syndrome colorectal, gastric, pancreatic cancer
MUTYH	Base excision repair	MUTYH-associated polyposis
BRCA1/BRCA2, ATM, PALB2	Double-strand break repair	Familial pancreatic and gastric cancers
TP53	Tumor suppressor, DNA damage response	CRC, gastric, pancreatic, hepatocellular carcinoma
Genes involved in cell adhesion and structural integrity[11]
CDH1	E-cadherin (cell-cell adhesion)	Hereditary diffuse gastric cancer
CTNNA1	Catenin alpha-1 (adherens junctions)	HDGC
SMAD4, BMPR1A	TGF-β pathway mediators	Juvenile polyposis syndrome, pancreatic cancer
Genes regulating inflammation and immune response[12]
NOD2	Innate immunity, bacterial sensing	Crohn’s disease
IL23R, IL10, IL12B	Cytokine signaling	IBD susceptibility
IRGM, ATG16 L1	Autophagy genes	Crohn’s disease
HLA-DQA1/HLA-DQB1	Antigen presentation	Celiac disease
TLR4, TLR9	Pattern recognition receptors	Functional dyspepsia, IBD
Genes involved in bile acid transport and cholestasis[13]
ABCB11	Bile salt export pump	PFIC2, BRIC
ABCC2 (MRP2)	Bile excretion	Dubin-Johnson syndrome
ATP8B1	Phospholipid transporter	PFIC1
TJP2	Tight junction protein	PFIC4
Genes in neuronal/gut motility and enteric nervous system[14]
RET, EDNRB, GDNF	ENS development	Hirschsprung’s disease
SCN5A	Sodium channel in ICCs/ENS	IBS with constipation
NEUROG3	Enteroendocrine differentiation	Congenital malabsorptive diarrhoea
Genes affecting nutrient absorption and metabolism[15]
LCT	Lactase enzyme	Lactose intolerance
SAR1B	Chylomicron transport	Chylomicron retention disease
SLC26A3	Cl-/HCO3- exchange	Congenital chloride diarrhea
SLC5A1 (SGLT1)	Glucose transport	Glucose-galactose malabsorption
Genes in oncogenic signaling and growth factors[15]
KRAS, NRAS	MAPK signaling	CRC, pancreatic cancer
BRAF	Downstream of KRAS	CRC (BRAF V600E in MSI tumors)
PIK3CA	PI3K/AKT pathway	CRC, gastric cancer
EGFR, HER2 (ERBB2)	Receptor tyrosine kinases	Gastric, colorectal cancers
FGFR2, IDH1/IDH2	Growth factor pathways	Cholangiocarcinoma
Genes related to epigenetic and transcriptional regulation[16]
ARID1A	Chromatin remodeling	Biliary cancer, CRC, gastric
MLH3, MSH3	Mismatch repair (minor MMR genes)	Polyposis syndromes
TET2, DNMT3A	DNA methylation regulation	CRC and inflammatory epigenetic signatures

MMR: Mismatch repair; CRC: Colorectal cancer; HDGC: Hereditary diffuse gastric cancer; TGF-β: Transforming growth factor-beta; IBD: Inflammatory bowel disease; PFIC: Progressive familial intrahepatic cholestasis; BRIC: Benign recurrent intrahepatic cholestasis; ENS: Enteric nervous system; ICCs: Interstitial cells of Cajal; IBS: Irritable bowel syndrome; Cl^-: Chloride ion; HCO₃^-: Bicarbonate ion; MAPK: Mitogen activated protein kinase; MSI: Microsatellite instability; PI3K: Phosphoinositide 3-kinase; AKT: Protein kinase B.