SEPTIN2
Chr 2septin 2
Also known as: DIFF6, NEDD-5, NEDD5, Pnutl3, SEPT2, Septin-2, hNedd5
SEPTIN2 encodes a filament-forming cytoskeletal GTPase that is essential for actin cytoskeleton organization, mitotic spindle function, ciliogenesis, and sperm tail structural integrity. Mutations cause autosomal recessive primary ciliary dyskinesia with reduced generation of multiple motile cilia, presenting with respiratory symptoms, situs abnormalities, and male infertility. The gene shows significant constraint against loss-of-function variants (LOEUF 0.496), indicating that complete loss of function is likely deleterious.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SEPTIN2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools