Case | Status | Pathogenic factor (s) for clinical relevance | Mutation gene | Nucleotide change | Effect on coding sequence (a.a change) | Region (exon) | Type of inheritance | Race/ethnicity | Ref |
---|---|---|---|---|---|---|---|---|---|
Proband 1 | HTZ missense | Proline residue, high mature: precursor ratio of uromodulin protein | UMOD | c.C518G | p.P173R | 4 | AD | Japan | [10] |
Proband 2 | HTZ missense | Altered evolutionary conserved residues in encoding UMOD gene | UMOD | c.187T>C | p.Cys63Arg | 3 | AD | Korea | [11] |
Proband 3 | HTZ missense | Co-segregation with disease, altered cysteine residue of uromodulin | UMOD | c.1382C>A | p.Ala461Glu | 6 | AD | Korea | [12] |
Proband 4 | HTZ missense | Co-segregation of disease phenotypes | UMOD | c0.667 TG | G, p.223, Cysteine | 3 | AD | China | [19] |
Proband 5 | missense | Ca-binding EGF-like domains of uromodulin protein | UMOD | c.189C > G | C63W | 4 | AD | Turkey | [20] |
Proband 6 | HTZ missense | Mutation in UMOD encoding uromodulin protein (THP) | UMOD | c.920A → C | p.K307 T | 5 | AD | Portugal | [21] |
Proband 7 | Sequence variant | Loss of a cysteine residue in the EGF domain of uromodulin protein | UMOD | c (0).2297> C | Cys77Arg | 4 | AD | Poland | [24] |
Proband 8 | HTZ substitution | Aminoacid substitution | UMOD | T403G | c.135G | 4 | AD | Japan | [25] |
Proband 9 | Homo nonsense | Aminoacid substitution | UMOD | c.589G>T | p.E197X | 3 | AD | Iran | [26] |
Proband 10 | HTZ missense | Altered evolutionary conserved residues in encoding UMOD gene | UMOD | c.688T>C | p. Trp 230Arg | 4 | AD | Japan | [27] |
Proband 11 | No gene mutation identified | No causal gene identified, new monogenic cause | UMOD, REN, HNF1β-negative | – | – | – | AD | UK | [28] |
Proband 12 | HTZ transversion mutation | Aminoacid substitution and significant conformational change | UMOD | c.891T>G | p.C297W | 4 | AD | Hungary | [29] |
Proband 13 | HTZ transversion mutation | Aminoacid substitution and significant conformational change | UMOD | c.891T>G | p.C297W | 4 | AD | Hungary | [29] |
Proband 14 | HTZ transversion mutation | Aminoacid substitution and significant conformational change | UMOD | c.891T>G | p.C297W | 4 | AD | Hungary | [29] |
Proband 15 | HTZ transversion mutation | Aminoacid substitution and significant conformational change | UMOD | c.891T>G | p.C297W | 4 | AD | Hungary | [29] |
Proband 16 | missense mutation | 1. Conserved cysteine to glycine aminoacid substitution in uromodulin zona pollucida domain 2. Delay protein export to the PM due to insertion in ER 3. Uromodulin deficiency 4. Co-segregation | UMOD | c.1039T>G | p.C347G | 6 | AD | Berlin | [32] |
Proband 17 | Missense mutation | 1. conserved cysteine to glycine aminoacid substitution in uromodulin zona pollucida domain 2. delay protein export to the PM due to insertion in ER 3. Uromodulin Deficiency 4. Co-segregation | UMOD | 1039T>G | p.C347G | 6 | AD | Berlin | [32] |
Proband 18 | HTZ | 1. Co-segregation | UMOD | C744G | Cys248Trp | 6 | AD | Italy | [33] |
Proband 19 | HTZ | 1.Reduction of urinary excretion of UMOD 2. Co-segregation | UMOD | C744G | Cys248Trp | 4 | AD | Turkey | [33] |
Proband 20 | HTZ | Co-segregation | UMOD | C744G | Cys248Trp | 4 | AD | German | [33] |
Proband 21 | HTZ | Reduction of urinary excretion of UMOD | UMOD | C744G | Cys248Trp | 4 | AD | Switzerland | [33] |
Proband 22 | HTZ | 1. Highly conserved of the cysteine residues in the UMOD protein throughout evolution 2. Co-segregation | UMOD | T229G | Cys77Gly | 4 | AD | USA | [33] |
Proband 23 | HTZ missense | 1. Altered disulfide bond formation due to substitution, retention in ER leading to unfolded protein response and apoptosis 2. Highly conserved of the cysteine residues in the UMOD protein throughout evolution 3. Co-segregation | UMOD | c.949T>G | p.C317G | 5 | AD | India | [38] |
Proband 24 | HTZ missense | 1. Altered disulfide bond formation due to substitution, retention in ER leading to unfolded protein response and apoptosis 2. Highly conserved of the cysteine residues in the UMOD protein throughout evolution 3. Co-segregation | UMOD | c.949T>G | p.C317G | 5 | AD | India | [38] |
Proband 25 | HTZ missense | Mutation in EGF1 domain, misfolding of the UMOD protein | UMOD | c.163G>A | p.Gly55Ser | 4 | AD | Brazil | [42] |
Proband 26 | – | – | UMOD | – | – | – | AD | USA | [43] |
Proband 27 | Homozyous missense | – | UMOD | c.263G>A | p.Gly88Asp | – | AR | Turkey | [44] |
Proband 28 | HTZ missense | ZP domain of uromodulin protein | UMOD | c.1648G>A | p.V550I | 8 | AD | China | [45] |
Proband 29 | – | – | UMOD | c.517G>A | p.proP173Ala | 3 | AD | Spain | [46] |
Probands 30 | HTZ | Protein deposits of misfolded uromodulin leading to misfolded protein accumulation in ER and ER stress, absence of uromodulin in apical membranes | UMOD | c.707C>G | p.pro236Arg | 3 | AD | Caucasian | [47] |
Proband 31 | HTZ missense | 1. Accumulation of uromodulin into ER 2. Maturation impairement 3. Severe reduction of uromodulin excretion | UMOD | c.C317Y | 950G>A | 5 | AD | Italy | [48] |
Proband 32 | HTZ missense | 1. Accumulation of uromodulin into ER 2. Maturation impairement 3. Severe reduction of uromodulin excretion | UMOD | c.C317Y | 950G>A | 5 | AD | Italy | [48] |
Proband 33 | HTZ missense | 1. Accumulation of uromodulin into ER 2. Maturation impairement 3. Severe reduction of uromodulin excretion | UMOD | c.C317Y | 950G>A | 5 | AD | Italy | [48] |
Proband 34 | HTZ missense | 1. Accumulation of uromodulin into ER 2. Maturation impairement 3. Severe reduction of uromodulin excretion | UMOD | c.C317Y | 950G>A | 5 | AD | Italy | [48] |
Proband 35 | HTZ missense | 1. Accumulation of uromodulin into ER 2. Maturation impairement 3. Severe reduction of uromodulin excretion | UMOD | c.C317Y | 950G>A | 5 | AD | Italy | [48] |
Proband 36 | HTZ missense | 1. Accumulation of uromodulin into ER 2. Maturation impairement 3. Severe reduction of uromodulin excretion | UMOD | c.C317Y | 950G>A | 5 | AD | Italy | [48] |
Proband 37 | HTZ missense | 1. Accumulation of uromodulin into ER 2. Maturation impairement 3. Severe reduction of uromodulin excretion | UMOD | c.C317Y | 950G>A | 5 | AD | Italy | [48] |
Proband 38 | HTZ missense | 1. Accumulation of uromodulin into ER 2. Maturation impairement 3. Severe reduction of uromodulin excretion | UMOD | c.C315R | 943T>C | 5 | AD | Italy | [48] |
Proband 39 | HTZ missense | 1. Accumulation of uromodulin into ER 2. Maturation impairement 3. Severe reduction of uromodulin excretion | UMOD | c.C315R | 943T>C | 5 | AD | Italy | [48] |
Proband 40 | HTZ missense | 1. Accumulation of uromodulin into ER 2. Maturation impairement 3. Severe reduction of uromodulin excretion | UMOD | c.C315R | 943T>C | 5 | AD | Italy | [48] |