Chronic kidney disease: genes and variants

Genes linked to Chronic kidney disease

• COL4A5: Collagen alpha-5(IV) chain

  It is essential for the alpha3-alpha4-alpha5 type IV collagen network that gives glomerular and cochlear basement membranes their mature mechanical properties. Pathogenic variants cause X-linked Alport syndrome, with progressive kidney disease, hearing loss, and characteristic ocular findings.

  1 disease-causing and 0 uncertain variants in COL4A5 are linked to Chronic kidney disease.

• AGTR1: Type-1 angiotensin II receptor

  Its activation by angiotensin II promotes vasoconstriction, aldosterone release, sodium retention, and vascular remodeling. Excessive signaling contributes to hypertension and cardiovascular disease, and the pathway is therapeutically blocked by angiotensin-receptor blockers.

  0 disease-causing and 0 uncertain variants in AGTR1 are linked to Chronic kidney disease.

• APOL1: Apolipoprotein L1

  It contributes to innate immunity and can form membrane pores that kill certain trypanosomes. The G1 and G2 risk variants provide protection against some African trypanosomes but markedly increase susceptibility to several forms of kidney disease in individuals carrying two risk alleles.

  0 disease-causing and 0 uncertain variants in APOL1 are linked to Chronic kidney disease.

• CASR: Extracellular calcium-sensing receptor

  It senses extracellular calcium in the parathyroid gland and kidney and adjusts parathyroid-hormone secretion and renal calcium handling accordingly. Loss-of-function variants cause familial hypocalciuric hypercalcemia or neonatal severe hyperparathyroidism, whereas activating variants cause autosomal dominant hypocalcemia.

  0 disease-causing and 0 uncertain variants in CASR are linked to Chronic kidney disease.

• FTO: Alpha-ketoglutarate-dependent dioxygenase FTO

  It removes selected methyl modifications from RNA and participates in regulation of energy balance and cellular metabolism. Common intronic variation at the FTO locus has one of the strongest replicated genetic associations with body-mass index and obesity risk.

  0 disease-causing and 0 uncertain variants in FTO are linked to Chronic kidney disease.

• GHR: Growth hormone receptor

  Its activation by growth hormone triggers JAK2-STAT signaling that promotes IGF-1 production, linear growth, and metabolic effects. Biallelic or dominant-negative loss-of-function variants can cause growth-hormone insensitivity, while activating alterations are rare.

  0 disease-causing and 0 uncertain variants in GHR are linked to Chronic kidney disease.

• PKD1: Polycystin-1

  Together with polycystin-2, it participates in tubular signaling, mechanosensation, and maintenance of renal epithelial architecture. Loss-of-function variants are the most common cause of autosomal dominant polycystic kidney disease.

  0 disease-causing and 0 uncertain variants in PKD1 are linked to Chronic kidney disease.

• PKD2: Polycystin-2

  It provides calcium-permeable polycystin channel activity and forms signaling complexes with polycystin-1 in renal epithelial cells. Loss-of-function variants cause autosomal dominant polycystic kidney disease, generally with a milder average course than PKD1-associated disease.

  0 disease-causing and 0 uncertain variants in PKD2 are linked to Chronic kidney disease.

• SLC12A3: Solute carrier family 12 member 3

  It reabsorbs sodium and chloride in the distal convoluted tubule and is a major determinant of renal salt and magnesium handling. Biallelic loss-of-function variants cause Gitelman syndrome with hypokalemic metabolic alkalosis, hypomagnesemia, and low urinary calcium.

  0 disease-causing and 0 uncertain variants in SLC12A3 are linked to Chronic kidney disease.

• SLC22A2: Solute carrier family 22 member 2

  It transports organic cations from blood into renal proximal-tubule cells and is important for elimination of drugs such as metformin and cisplatin. Functional variants and drug interactions can alter renal drug clearance and toxicity.

  0 disease-causing and 0 uncertain variants in SLC22A2 are linked to Chronic kidney disease.

• SLC5A2: Sodium/glucose cotransporter 2

  It reabsorbs most filtered glucose from the renal proximal tubule together with sodium. Loss-of-function variants cause familial renal glucosuria, while pharmacologic inhibition lowers blood glucose and provides major cardiovascular and kidney benefits.

  0 disease-causing and 0 uncertain variants in SLC5A2 are linked to Chronic kidney disease.

• UMOD: Uromodulin

  It is secreted by thick-ascending-limb cells into urine, where it contributes to salt handling, urinary defense, and protection against kidney stones. Dominant pathogenic variants cause autosomal dominant tubulointerstitial kidney disease, while common regulatory variants influence kidney-function and hypertension risk.

  0 disease-causing and 0 uncertain variants in UMOD are linked to Chronic kidney disease.

• VDR: Vitamin D3 receptor

  It converts active vitamin D binding into transcriptional programs that regulate calcium and phosphate balance, bone mineralization, and many tissue-specific functions. Biallelic loss-of-function variants cause hereditary vitamin-D-resistant rickets with hypocalcemia, secondary hyperparathyroidism, and impaired bone mineralization.

  0 disease-causing and 0 uncertain variants in VDR are linked to Chronic kidney disease.

Weakly linked (only a few uncertain records): COL4A4, NPHS2, APOA1, COL4A3 and ETFB.

Known disease-causing variants in Chronic kidney disease

Same protein, different disease

• X-linked Alport syndrome is also caused by COL4A5 variants; they fall mostly in different places as the Chronic kidney disease variants (341 disease-causing).
• Alport syndrome is also caused by COL4A5 variants; they fall mostly in different places as the Chronic kidney disease variants (14 disease-causing).

Diseases related to Chronic kidney disease

• Kidney disorder, also linked to AGTR1, APOL1, COL4A5, PKD1 and 2 more
• Type 2 diabetes mellitus, also linked to AGTR1, FTO and SLC5A2
• Diabetes mellitus, also linked to AGTR1, FTO and SLC5A2
• Polycystic kidney disease, adult type, also linked to PKD1 and PKD2
• Nephrotic syndrome, also linked to COL4A5 and SLC12A3
• Autosomal dominant polycystic kidney disease, also linked to PKD1 and PKD2
• Polycystic kidney disease, also linked to PKD1 and PKD2
• Myocardial infarction, also linked to AGTR1 and SLC12A3
• Meckel syndrome, also linked to PKD1 and PKD2
• Hypercholesterolemia, familial, 1, also linked to GHR
• Hypertrophic cardiomyopathy, also linked to CASR
• X-linked Alport syndrome, also linked to COL4A5

Frequently asked questions

Which genes are linked to Chronic kidney disease?

In CATVariant, Chronic kidney disease is linked to 13 analyzed proteins: COL4A5 (Collagen alpha-5(IV) chain), AGTR1 (Type-1 angiotensin II receptor), APOL1 (Apolipoprotein L1), CASR (Extracellular calcium-sensing receptor), FTO (Alpha-ketoglutarate-dependent dioxygenase FTO), GHR (Growth hormone receptor) and 7 more.

How many genetic variants are linked to Chronic kidney disease?

8 variants: 1 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 2 are of uncertain significance or have conflicting reports.

Which uncertain variants in Chronic kidney disease look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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