Fig 2: Immunoglobulin occurs in a kidney intrinsic manner(A) Schematic demonstrating experiment design testing kidney-intrinsic predisposition to kidney disease.(B) Immunofluorescence of immunoglobulin G (red), podocin (green) and DAPI in cryosections from 8-week-old mice of B cell deficient Vangl1+/− and Vangl1+/+ mice injected with IgG.(C) Scoring of immunofluorescent IgG deposition in mice post injection. Data are represented as median, Mann-Whitney U, p = 0.02.

Fig 3: Intronic deletions in VANGL1 associate with kidney disease(A) Association of copy number variation in VANGL1 detected by qPCR with the presence or absence of nephritis in SLE (n = 177); χ2 2d.f., p < 0.0001 (LN = lupus nephritis).(B) Comparison of MAF of VANGL1 CNV in esv3587290 in gnomAD global and Tiwi Islander populations (n = 120); Fisher’s exact, p < 0.0001).(C) Representative whole genome sequencing reads of intronic deletion in VANGL1 of the maximum length reported for the CNV.(D) Comparison of relative VANGL1 expression in PBMCs from (i) SLE patients with 0 or 2 copies of VANGL1, (ii) Healthy controls or SLE patients with or without lupus nephritis.e) RNaseq read alignment demonstrating skipping of exon 2 in a patient homozygous for the VANGL1 CNV with read covering exon 1 and exon 3 highlighted in yellow.

Fig 4: Vangl1+/− does not alter glomerular development(A) Representative H&E stain of glomerular sections from 8-week-old Vangl1+/− and Vangl1+/+ (n = 6/group).(B) Comparison of kidney volume, glomerular size and glomeruli/light field in 8-week-old mice of indicated genotype.(C) Serum creatinine and urine albumin in 16-week-old Vangl1+/− and Vangl1+/+ mice.(D) ANA from 16-week-old mice of indicated genotype(E) Serum immunoglobulin of 12-month-aged mice of indicated genotype. Data are represented as median throughout.