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Recent next‑generation sequencing studies in patients with steroid‑resistant nephrotic syndrome (SRNS) have included NRBP1 (HGNC:7993) among a panel of genes screened for disease‐causing variants (PMID:26248470) (PMID:26467726). However, while these studies encompassed cohorts of 37 and 24 patients respectively, NRBP1 was reported only as an incidental finding without identification of any NRBP1‑specific pathogenic variants.
The overall clinical validity of the NRBP1‑SRNS association is therefore limited. No NRBP1 variant meeting the established criteria was described, and no segregation data or family studies were provided to support a causative role. In both studies, secondary variants in NRBP1 were flagged during multi‑gene screening, but their pathogenic relevance remains unclear (PMID:26248470).
From a genetic perspective, the lack of reported NRBP1 variants (i.e. no HGVS‐compliant coding changes such as a c. variant featuring a corresponding p. amino‑acid alteration) precludes detailed assessment of the variant spectrum. This absence of NRBP1‑specific mutational events diminishes the strength of the genetic evidence. Consequently, no segregation of a candidate allele among multiple affected relatives has been documented in cases of SRNS.
Functional data supporting a mechanistic link between NRBP1 and SRNS are also lacking. There have been no functional assays, expression studies, animal models, or rescue experiments published that directly evaluate the role of NRBP1 in podocyte biology or renal pathology. This deficiency in experimental evidence further underscores the uncertainty regarding the gene’s contribution to disease pathogenesis.
In summary, while NRBP1 is included within genetic panels for SRNS, the current evidence comprises only incidental secondary findings with no reported NRBP1‑specific variants, lack of segregation support, and no functional validation. Thus, the relationship between NRBP1 and steroid‑resistant nephrotic syndrome remains limited and should be interpreted with considerable caution in a diagnostic setting.
Key take‑home sentence: Until additional targeted genetic and functional studies are conducted, NRBP1 should be regarded as a candidate gene with limited clinical utility for the diagnosis of steroid‑resistant nephrotic syndrome.
Gene–Disease AssociationLimitedNRBP1 has been incidentally identified in SRNS panels among cohorts of 37 (PMID:26248470) and 24 (PMID:26467726) patients, without NRBP1‑specific variants or segregation data. Genetic EvidenceLimitedNo NRBP1‑specific coding changes meeting HGVS criteria (e.g. a c. variant with corresponding p. change) were reported; variants in NRBP1 were only noted as incidental secondary findings lacking replication or segregation evidence. Functional EvidenceLimitedThere are no functional studies, animal models, or rescue experiments that directly assess the role of NRBP1 in steroid‑resistant nephrotic syndrome, limiting mechanistic insights. |