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This summary outlines the association between NKAPL (HGNC:21584) and schizophrenia (MONDO_0005090) based on multiple case‑control and genetic studies in Han Chinese populations. Schizophrenia is a complex, highly heritable disorder with numerous genetic risk factors, and NKAPL has emerged as one of the candidate genes of interest. The evidence spans common variants, including significant SNP associations, and rare variants identified through targeted resequencing efforts.
In the initial study, resequencing of NKAPL in 515 schizophrenia patients (PMID:24972756) and 456 controls revealed five common SNPs. Notably, the minor allele (A) of rs1635 showed significant association with schizophrenia (P = 0.0003, OR = 1.41) and a risk haplotype was defined. Additionally, four patient‑specific rare SNPs were identified, one of which—c.844G>A (p.Ala282Thr)—illustrates the type of rare coding variant contributing to disease susceptibility.
A subsequent replication study in an independent cohort (902 cases and 1,091 controls, PMID:23437227) further supported the association. This investigation evaluated multiple SNPs in the region, including those in NKAPL, and confirmed significant differences in allele frequencies. The convergent findings of both studies underscore a robust genetic contribution of NKAPL variants to schizophrenia risk.
Despite solid genetic association data, functional evidence for NKAPL’s role in schizophrenia remains limited. In silico analyses predict a potential impact of the rare variants on protein function, but experimental assessments are still rudimentary. No detailed mechanistic studies have yet demonstrated how these NKAPL variants alter cellular pathways, leaving the pathogenic mechanism to be more fully explored.
Integrating the genetic and preliminary functional data, the current evidence supports a strong gene‑disease association for NKAPL in schizophrenia. The recurrent identification of risk alleles and haplotypes in independent cohorts provides a compelling argument for the diagnostic relevance of NKAPL testing in clinical settings. It is anticipated that further functional studies will augment these findings and enable more precise therapeutic strategies.
Key take‑home sentence: The consistent association of NKAPL variants with schizophrenia across diverse studies highlights its potential utility in risk assessment and precision medicine for this complex disorder.
Gene–Disease AssociationStrongRobust case‑control data from 515 patients ([PMID:24972756]) and 902 patients ([PMID:23437227]) along with significant SNP and haplotype associations provide strong support for the NKAPL-schizophrenia link. Genetic EvidenceStrongBoth common variant (rs1635) associations and the identification of rare, patient‑specific variants such as c.844G>A (p.Ala282Thr) across independent cohorts indicate compelling genetic evidence. Functional EvidenceLimitedWhile in silico analyses suggest a functional impact of the rare variants, the experimental data remains rudimentary and further functional studies are needed to clarify the pathogenic mechanism. |