SEPTIN5
Chr 22septin 5
Also known as: CDCREL, CDCREL-1, CDCREL1, H5, HCDCREL-1, PNUTL1, SEPT5, Septin-5
SEPTIN5 encodes a filament-forming cytoskeletal GTPase that regulates cytoskeletal organization and may function in cytokinesis and platelet secretion. The gene is highly constrained against loss-of-function variants and is located in the 22q11 region that is frequently deleted in DiGeorge and velocardiofacial syndromes. Mutations in SEPTIN5 itself have not been established as a cause of Mendelian disease, though the gene's involvement in chromosomal rearrangements has been reported in acute myeloid leukemia.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative, gain-of-function and loss-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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SEPTIN5 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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