Variant Synonymizer: Platform to identify mutations defined in different ways is available now!
Over 2,000 gene–disease validation summaries are now available—no login required!
In a study screening four candidate genes in 90 unrelated Chinese patients with hypospadias, rare heterozygous variants were identified, including a missense change in HOXB6 (c.367T>C (p.Cys123Arg)) that was absent from 380 control chromosomes (PMID:17003840). Although the overall number of HOXB6-specific variants is low, the detection in more than one proband provides modest genetic evidence for its involvement, despite the absence of segregation data from affected relatives.
A subsequent large-scale candidate gene association study also reported single nucleotide polymorphisms in HOXB6 among other developmental genes associated with hypospadias (PMID:23727413). In the absence of direct functional or experimental evidence for HOXB6, the current data rely on in silico predictions and the conservation of altered amino acids. Key take‑home: Although the evidence remains limited, HOXB6 should be considered a potential candidate for hypospadias risk, meriting further functional validation to support its clinical utility.
Gene–Disease AssociationLimitedHOXB6 variants were identified in a limited number of cases (2 variants in 90 probands) without segregation data (PMID:17003840), supported by additional SNP association evidence (PMID:23727413). Genetic EvidenceLimitedTwo heterozygous missense variants in HOXB6, notably c.367T>C (p.Cys123Arg), were reported in a case series, suggesting a tentative genetic association with hypospadias, though larger cohorts and segregation analysis are needed. Functional EvidenceLimitedNo direct functional studies for HOXB6 have been provided; current evidence relies on in silico predictions and conservation data without experimental validation. |