Kidney disorder: genes and variants

Genes linked to Kidney disorder

• WT1: Wilms tumor protein

  It controls transcriptional programs required for kidney and gonadal development and also restrains or promotes cell growth in a context-dependent manner. Germline pathogenic variants cause Wilms-tumor predisposition and Denys-Drash or Frasier syndromes, while somatic alterations occur in some leukemias.

  2 disease-causing and 0 uncertain variants in WT1 are linked to Kidney disorder.

• NPHS1: Nephrin

  It forms a key structural and signaling component of the slit diaphragm between glomerular podocyte foot processes. Biallelic loss-of-function variants cause congenital nephrotic syndrome of the Finnish type with massive protein loss beginning early in life.

  1 disease-causing and 4 uncertain variants in NPHS1 are linked to Kidney disorder.

• 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 2 uncertain variants in COL4A5 are linked to Kidney disorder.

• 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 3 uncertain variants in UMOD are linked to Kidney disorder.

• 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 Kidney disorder.

• 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 Kidney disorder.

• 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 Kidney disorder.

• 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 Kidney disorder.

• SLC12A1: Solute carrier family 12 member 1

  It reabsorbs sodium, potassium, and chloride in the thick ascending limb of the kidney, helping generate the medullary concentration gradient and maintain salt balance. Biallelic loss-of-function variants cause Bartter syndrome type 1 with renal salt wasting.

  0 disease-causing and 0 uncertain variants in SLC12A1 are linked to Kidney disorder.

• COL4A3: Collagen alpha-3(IV) chain

  It contributes to the alpha3-alpha4-alpha5 type IV collagen network that forms the specialized basement membrane of the renal glomerulus, cochlea, and eye. Pathogenic variants cause Alport-spectrum disease and thin-basement-membrane nephropathy, with variable kidney and hearing involvement.

  0 disease-causing and 3 uncertain variants in COL4A3 are linked to Kidney disorder.

Weakly linked (only a few uncertain records): CEP290, COL4A4, REN and SLC34A3.

Known disease-causing variants in Kidney disorder

Same protein, different disease

• Wilms tumor is also caused by WT1 variants; they fall mostly in different places as the Kidney disorder variants (6 disease-causing).
• 11p partial monosomy syndrome is also caused by WT1 variants; they fall mostly in different places as the Kidney disorder variants (5 disease-causing).
• Finnish congenital nephrotic syndrome is also caused by NPHS1 variants; they fall mostly in different places as the Kidney disorder variants (70 disease-causing).
• Nephrotic syndrome is also caused by NPHS1 variants; they fall mostly in different places as the Kidney disorder variants (4 disease-causing).
• X-linked Alport syndrome is also caused by COL4A5 variants; they fall mostly in different places as the Kidney disorder variants (341 disease-causing).
• Alport syndrome is also caused by COL4A5 variants; they fall mostly in different places as the Kidney disorder variants (14 disease-causing).

Diseases related to Kidney disorder

• Chronic kidney disease, also linked to AGTR1, APOL1, COL4A5, PKD1 and 2 more
• Nephrotic syndrome, also linked to COL4A5, NPHS1, SLC12A1 and WT1
• Alport syndrome, also linked to COL4A3 and COL4A5
• Autosomal dominant Alport syndrome, also linked to COL4A3 and COL4A5
• Polycystic kidney disease, adult type, also linked to PKD1 and PKD2
• Autosomal dominant polycystic kidney disease, also linked to PKD1 and PKD2
• Polycystic kidney disease, also linked to PKD1 and PKD2
• Focal segmental glomerulosclerosis, also linked to APOL1 and NPHS1
• Meckel syndrome, also linked to PKD1 and PKD2
• X-linked Alport syndrome, also linked to COL4A5
• Autosomal recessive Alport syndrome, also linked to COL4A3
• Hematuria, benign familial, also linked to COL4A3

Frequently asked questions

Which genes are linked to Kidney disorder?

In CATVariant, Kidney disorder is linked to 10 analyzed proteins: WT1 (Wilms tumor protein), NPHS1 (Nephrin), COL4A5 (Collagen alpha-5(IV) chain), UMOD (Uromodulin), AGTR1 (Type-1 angiotensin II receptor), APOL1 (Apolipoprotein L1) and 4 more.

How many genetic variants are linked to Kidney disorder?

36 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 19 are of uncertain significance or have conflicting reports.

Which uncertain variants in Kidney disorder 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.

Download every variant as CSV · Browse all diseases · Methods · About the Center