SNX19
Chr 11sorting nexin 19
Also known as: CHET8
SNX19 encodes a sorting nexin protein that regulates intracellular vesicle trafficking and exocytosis, particularly maintaining insulin-containing dense core vesicles in pancreatic beta-cells and facilitating insulin secretion. Biallelic mutations cause autosomal recessive early-onset diabetes mellitus with additional features including microcephaly and intellectual disability. The gene is not highly constrained against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function 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
264 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 74 | 0 | 74 |
Likely Pathogenic | 0 | 0 | 7 | 0 | 7 |
VUS | 1 | 142 | 4 | 0 | 147 |
Likely Benign | 0 | 8 | 0 | 4 | 12 |
Benign | 0 | 3 | 0 | 0 | 3 |
| Total | 1 | 153 | 85 | 4 | 243 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SNX19 · 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