Deletions in VANGL1 are a risk factor for antibody-mediated kidney disease

Jiang, Simon H., Mercan, Sevcan, Papa, Ilenia, Moldovan, Max, Walters, Giles D., Koina, Mark, Fadia, Mitali, Stanley, Maurice, Lea-Henry, Tom, Cook, Amelia, Ellyard, Julia, McMorran, Brendan, Sundaram, Madhivanan, Thomson, Russell, Canete, Pablo F., Hoy, Wendy, Hutton, Holly, Srivastava, Monika, McKeon, Kathryn, de la Ru´a Figueroa, In˜igo, Cervera, Ricard, Faria, Raquel, D'Alfonso, Sandra, Gatto, Mariele, Athanasopoulos, Vicki, Field, Matthew, Mathews, John, Cho, Eun, Andrews, Thomas D., Kitching, A. Richard, Cook, Matthew C., Alarcon Riquelme, Marta, Bahlo, Melanie, and Vinuesa, Carola G. (2021) Deletions in VANGL1 are a risk factor for antibody-mediated kidney disease. Cell Reports Medicine, 2. 100475.

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We identify an intronic deletion in VANGL1 that predisposes to renal injury in high risk populations through a kidney-intrinsic process. Half of all SLE patients develop nephritis, yet the predisposing mechanisms to kidney damage remain poorly understood. There is limited evidence of genetic contribution to specific organ involvement in SLE.(1,2) We identify a large deletion in intron 7 of Van Gogh Like 1 (VANGL1), which associates with nephritis in SLE patients. The same deletion occurs at increased frequency in an indigenous population (Tiwi Islanders) with 10-fold higher rates of kidney disease compared with non-indigenous populations. Vangl1 hemizygosity in mice results in spontaneous IgA and IgG deposition within the glomerular mesangium in the absence of autoimmune nephritis. Serum transfer into B cell-deficient Vangl1(+/-) mice results in mesangial IgG deposition indicating that Ig deposits occur in a kidney-intrinsic fashion in the absence of Vangl1. These results suggest that Vangl1 acts in the kidney to prevent Ig deposits and its deficiency may trigger nephritis in individuals with SLE.

Item ID: 72280
Item Type: Article (Research - C1)
ISSN: 2666-3791
Keywords: glomerulonephritis; antibody; immunoglobulin; lupus nephritis; genetic; autoimmune; chronic kidney disease
Copyright Information: © 2021 The Author(s). This is an open access article under the CC BY-NC-ND license (
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC project grant, NHMRC program grant
Date Deposited: 09 Feb 2022 12:47
FoR Codes: 31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310204 Genomics and transcriptomics @ 50%
31 BIOLOGICAL SCIENCES > 3105 Genetics > 310507 Genetic immunology @ 50%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions @ 100%
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