SPATA2 – Psoriasis

The association between SPATA2 and psoriasis is supported by multiple independent case‑control studies demonstrating significant genetic links. An initial genome‑wide association scan identified SNP rs495337 in the SPATA2 transcript in an initial cohort of 318 cases (PMID:18364390), and subsequent replication in a larger cohort of 2679 cases and 2215 controls reinforced this signal (PMID:18364390).

In a separate study on a Chinese population, SPATA2 was evaluated alongside four other candidate genes. Although only selected SNPs in HCP5, TNIP1, and TNFAIP3 reached statistical significance, the inclusion of SPATA2 in the genetic panel highlights its potential role in the multifactorial etiology of psoriasis (PMID:25264125).

A recent investigation in an eastern Indian cohort further strengthened the genetic association by showing that SNP rs495337 in SPATA2 conferred a 1.2‑fold increased risk in HLA‑Cw6 positive patients, supported by significant downregulation of SPATA2 in risk genotype carriers. This study utilized robust protein structural stability assessments to emphasize the deleterious impact of the associated coding variants on the SPATA2 protein (PMID:38409498).

Genetic evidence across these studies consistently identifies SPATA2 as a susceptibility gene for psoriasis. The recurrent association of the rs495337 locus across ethnically diverse populations lends strong credence to its role in the pathogenesis of the disease. Importantly, the consistent replication of this signal has contributed to an overall ClinGen gene‑disease association rating of Strong.

Supporting functional evidence, particularly from the eastern Indian study, demonstrates that altered SPATA2 expression and compromised protein stability may be central to its pathogenic mechanism. While early reports also referenced neighboring loci, subsequent expression and functional analyses have clarified that dysregulation of SPATA2 is likely contributory to the inflammatory cascade in psoriasis.

In summary, the combined genetic and functional evidence supports a strong role for SPATA2 in psoriasis, providing valuable insight for diagnostic decision‑making and potential therapeutic targeting. Key take‑home: SPATA2 emerges as a robust genetic contributor to psoriasis with consistent association across studies and moderate functional support, underscoring its clinical utility.

References

• Human Molecular Genetics • 2008 • Identification of ZNF313/RNF114 as a novel psoriasis susceptibility gene PMID:18364390
• International Journal of Immunogenetics • 2014 • Investigating the genetic association of HCP5, SPATA2, TNIP1, TNFAIP3 and COG6 with psoriasis in Chinese population PMID:25264125
• Journal of Human Genetics • 2024 • Identifying the genetic associations among the psoriasis patients in eastern India PMID:38409498

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