Table 1 Recessive mutations in NOS1AP (NM_014697) in families with nephrotic syndrome

From: Recessive variants in the intergenic NOS1AP-C1orf226 locus cause monogenic kidney disease responsive to anti-proteinuric treatment

Family _Individual

Nucleotide change

Amino acid change

Exon (Zyg, Seg)

In silico severity scores

Conservation

ExAC and gnomAD

SEX

PC

Renal disease

ACMG classification

B4606_21

c.1105+5 G > C

Splice

9 (hom, Y)

SSF-100% ME-100%

NNS-100%

GS-100%

N/A

NP

M

Y

Initial Onset: 3 years, edema

Urinalysis: Microscopic hematuria; 19 g protein/day

Serum studies: Cr 0.23 mg/dL, TP 4 g/dL, Albumin 2.2 g/dL, TG 9.98 mmol/L

Biopsy: FSGS

Treatment: SRNS, Partial response to CsA.

Pathogenic

(PS3, PM2, PM4, PP4, PP3)

VCV 001333195

Canonical c.1259 G > C

Intergenic c.1258+1 G > C

p.G420A

Splice

10 (hom)

SIFT t

MT b

PP2 b

SSF-100% ME -100%

NNS-100%

GS-100%

X. tropicalis

N/A

NP

M

Y

Initial Onset: Congenital NS

Renal function: ESKD at age 3 years

Course: Passed away at the age 5 years

RUS: Unilateral multicystic kidney

Pathogenic

(PVS1, PM2, PP1, PP3, PP4)

A1018a

(published)

c.428 G > A

p.C143Y

5 (hom, mat)

SIFT DL

MT DC PP2 PD

C. elegans

NP

M

Y

Initial Onset: 4 days, SGA, edema

Urinalysis: Microscopic hematuria; 18.5 g protein/g creatinine

Serum Studies: Cr 1.0 mg/dL (CKD), TP 4.8 g/dL.

RUS: N/A

Treatment: Resistant to corticosteroids, cyclophosphamide, cyclosporin A.

Biopsy: Mesangial cell proliferation, 75% podocyte foot effacement.

ESKD: 7 years (HD and TX).

Pathogenic (PS3, PM1, PM2, PP3, PP4)

A5106a

(published)

c.345-3 T > G

Splice

5 (hom)

SSF-5%

ME-66%

NNS-100%

GS-77%

N/A

NP

M

Y

Initial Onset: 6 months, edema

Urinalysis: Microscopic hematuria; 3 g protein/g creatinine.

Initial Renal Function: Cr 0.6 mg/dL (CKD).

RUS: Bilateral echogenicity

Treatment: Resistant to corticosteroids.

Pathogenic (PS3, PM2, PM1, PM4, PP3, PP4)

  1. CsA cyclosporine, CKD chronic kidney disease, Cr serum creatinine, DC disease causing, DL deleterious, ESKD end-stage kidney disease, ExAC v1.0 and gnomAD v2.11 and v3 summary of data within Exome and Genome Aggregation databases, FSGS focal segmental glomerulosclerosis, HD hemodialysis, hom homozygous, ME MaxEnt splice prediction score, NA not available, N/A not applicable, NS nephrotic syndrome, NNS NNSPLICE splice-site mutation prediction score, PC parental consanguinity, PD probably damaging, PP2 PolyPhen-2 prediction score, RUS renal ultrasound, SGA small for gestational age, SIFT “Sorting Tolerant From Intolerant” prediction score, Seg segregation, SRNS steroid-resistant nephrotic syndrome, TG triglycerides, TP total protein, TX kidney transplantation, Y yes, Zyg zygosity.
  2. aPublished in Majmundar, Buerger et al., Sci Adv 2021.
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