Table 1 Prioritized IBS-risk genes based on existing published statistical evidence
Gene | Chr location | Gene name | Gene function | Gene region | Phenotype | Key reference |
|---|---|---|---|---|---|---|
TNFSF15 | 9q32 | Tumor necrosis factor (ligand) superfamily, member 15 | Codes for TNF-like ligand 1A (TL1A), which contributes to the modulation of inflammatory responses. | Intron | IBS, IBS-C | [14] |
Intron and upstream | IBS-D | [15] | ||||
Intron | IBS-A | [16] | ||||
Intron | IBS, IBS-C | [17] | ||||
TLR9 | 3p21.3 | Toll-like receptor 9 | A Toll-like receptor that activate the immune system through recognition of specific patterns on microorganisms. | Intron and upstream | PI-IBS | [26] |
Upstream | IBS-D | [27] | ||||
HTR3E | 3q27.1 | 5-hydroxytryptamine (serotonin) receptor 3E, ionotropic | A receptor for serotonin, a neurotransmitter in the central nervous system and gastrointestinal tract. | 3′UTR | IBS-D | [28] |
NPSR1 | 7p14.3 | Neuropeptide S receptor 1 | Receptor for neuropeptide S, expressed in brain and enteroendocrine cells, involved in anxiety, inflammation, nociception, etc. | Intron and coding polymorphism | Colonic transit time, sensory ratings (pain, gas, urgency) | [19] |
5′ near gene and beginning of gene | RAP | [21] | ||||
KLB | 4p14 | Klotho beta | Co-receptor of fibroblast growth factor 19 (FGFR4) on hepatocyte membrane, required for suppression of bile acid synthesis in liver. | Coding polymorphism | Colonic transit in IBS-D | [9] |
SCN5A | 3p21 | Sodium channel, voltage gated, type V alpha subunit | Voltage-gated sodium channel (NaV1.5) in pacemaker cells of the heart and interstitial cells of cajal (ICC) cells of the gut important for smooth muscle contraction. | Rare coding mutations and signal of common SNPs in middle of gene | IBS, IBS-C | [13] |
CDC42 | 1p36.1 | Cell division cycle 42 | A small GTPase of the Rho-subfamily involved in cell cycle regulation and possibly epithelial barrier function through intestinal stem cell differentiation and proliferation. | Intron | IBS-C | [16] |
KDELR2 | 7p22.1 | KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 2 | Belongs to a family of KDEL motif binding receptors, mediating the retrograde transport of proteins to the endoplasmatic reticulum. | Intron | IBS | [25] |