Table 1.

Genes associated with typical and atypical ADTKD

Genes causing typical and atypical ADTKD (OMIM number)	Encoded protein	Protein functions/KO phenotypes
UMOD (*191845)	Uromodulin	Role in TAL/DCT electrolyte transport, regulation of electrolyte channels and transporters Role in urine concentration, blood pressure control Protection from UTI Protection from nephrolithiasis Role in immunomodulation and tubular recovery from injury Systemic role in granulopoiesis and as antioxidant No overt tubulointerstitial kidney disease in Umod KO mice
MUC1 (*158340)	Mucin 1	Protective epithelial mucous barrier Role in cell–cell interactions and sensing of the extracellular environment Role in immunomodulation Role in distal tubular Ca2+ transport (via TRPV5) Protective role in kidney ischaemia–reperfusion injury No overt tubulointerstitial kidney disease in Muc1 KO mice
REN (*179820)	Preprorenin	Catalyses angiotensinogen to angiotensin I conversion, role in systemic and local RAAS Role in nephrogenesis Renin-deficient mice die within 1 week after birth, low blood pressure, polyuria and hydronephrosis reported
HNF1B (*189907)	Hepatocyte nuclear factor 1β	Essential role during mouse early embryogenesis Epithelial transcription factor in several adult organs (kidney, pancreas and liver) Direct transcriptional regulation of cystic disease genes (Pkhd1, Pkd2) and Umod Hnf1β KO embryos show disorganized visceral endoderm and die at Day 7.5 of development Kidney-specific inactivation in mice leads to post-natal lethality, polycystic kidneys and renal failure
SEC61A1 (*609213)	α1 subunit of SEC61 translocon	Subunit of SEC61 mammalian translocon mediating transport of nascent polypeptides into the ER Involved in retrograde transport of membrane proteins from the ER to the cytosol for proteasomal degradation Allow Ca2+ leakage from the ER into the cytosol Knockdown of sec61a1 orthologue in zebrafish embryos results in pronephric TA
DNAJB11 (*611341)	DNAJ/HSP40 homolog, subfamily B, member 11 (cofactor of BiP)	Interacts with and regulates ER chaperone BiP (GRP78) activity by stimulating its ATPase activity Pre-weaning lethality, incomplete penetrance reported in KO mouse model (IMPC)

IMPC, International Mouse Phenotyping Consortium.