NPHS1
Chr 19ARNPHS1 adhesion molecule, nephrin
Also known as: CNF, NPHN, nephrin
The protein is a transmembrane cell adhesion molecule that forms part of the slit diaphragm in glomerular podocytes, functioning as an ultrafilter to prevent albumin and other plasma proteins from entering urine. Mutations cause autosomal recessive congenital nephrotic syndrome type 1 (Finnish-type), characterized by severe proteinuria beginning in infancy with loss of normal kidney filtration barrier structure. This gene is extremely intolerant to loss-of-function variants, reflecting its critical role in kidney development and function.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
400 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 6 | 0 | 6 | 0 | 12 |
Likely Pathogenic | 26 | 2 | 7 | 0 | 35 |
VUS | 0 | 195 | 38 | 14 | 247 |
Likely Benign | 0 | 4 | 29 | 48 | 81 |
Benign | 0 | 0 | 2 | 1 | 3 |
Conflicting | — | 21 | |||
| Total | 32 | 201 | 82 | 63 | 399 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NPHS1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Role of Finerenone in African American Veterans With Diabetic Kidney Disease
NOT YET RECRUITINGValidation, Implementation, and Cost-analysis of a Strategy for Personalized Diagnosis of Rare Kidney Diseases
RECRUITINGImplementation of a Diagnostic Workflow for Personalized Diagnosis of Nephrotic Syndrome
RECRUITINGExternal Resources
Links to major genomics databases and tools