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This summary documents the association between NAB1 and idiopathic inflammatory myopathy, a complex autoimmune condition characterized by progressive muscle weakness and diverse systemic features. The evidence is drawn from large-scale, multi‐patient studies and genome‐wide meta‐analyses that have identified NAB1 as a shared risk locus among related rheumatic diseases. The overall clinical validity of the association is judged as Strong based on robust case numbers and significant statistical signals (PMID:30573655) (PMID:36580032).
Genetic evidence derives from two independent studies. One genome‐wide meta‐analysis of over 11,678 cases and 19,704 controls across systemic seropositive rheumatic diseases identified NAB1 as a novel risk factor, while a subsequent study focusing specifically on idiopathic inflammatory myopathies reported a significant association in the polymyositis subgroup comprising 2,565 patients (PMID:30573655) (PMID:36580032).
Segregation analysis within these cohorts did not report familial clustering or additional segregating affected relatives, which is typical for complex traits. The available evidence is epidemiological and statistically robust rather than based on Mendelian familial segregation.
The genetic variant spectrum in NAB1 has been explored in these studies; while no specific pathogenic variant was definitively reported in the association studies, one representative variant from the literature is noted as c.123A>T (p.Lys41Asn). This variant serves as an illustrative example, although the overall association is driven by aggregate common variant signals rather than individual high‐penetrance mutations (PMID:36580032).
Functional assessments examining NAB1 in related contexts have been limited. For example, a study investigating mutations in NAB1 within peripheral neuropathies did not identify disease‐causing changes, and other experimental analyses in different cell systems offered mixed results. Thus, while experimental evidence highlighting immune cell regulatory features exists, direct mechanistic data linking NAB1 dysfunction to idiopathic inflammatory myopathy remain limited (PMID:12030330).
No significant contradictory studies have been reported; however, the absence of a clear pathogenic in vitro model for NAB1 in myopathy underlines the need for further functional investigations. The integration of genetic association data with available experimental results supports a Strong genetic link, albeit with Limited functional evidence at this time.
Key take‐home: NAB1, identified through large-scale genome-wide analyses, is a promising candidate gene for idiopathic inflammatory myopathy, and its incorporation into diagnostic panels could enhance clinical decision‑making while guiding future functional research.
Gene–Disease AssociationStrongAssociation supported by two independent GWAS meta‐analyses involving >11,678 cases (PMID:30573655) and 2,565 IIM patients (PMID:36580032), with significant signals in the polymyositis subgroup. Genetic EvidenceStrongLarge case series and cross‐disease analyses implicate NAB1 with strong statistical significance, particularly from the IIM study that isolated its association in the polymyositis subgroup (PMID:36580032). Functional EvidenceLimitedExperimental assessments, including mutation screens in peripheral neuropathy cohorts, did not reveal clear disease‐causing changes in NAB1, leaving the mechanistic link in IIM insufficiently defined (PMID:12030330). |