STON1
protein-codingstonin 1
Gene summary
Endocytosis of cell surface proteins is mediated by a complex molecular machinery that assembles on the inner surface of the plasma membrane. This gene encodes one of two human homologs of the Drosophila melanogaster stoned B protein. This protein is related to components of the endocytic machinery and exhibits a modular structure consisting of an N-terminal proline-rich domain, a central region of homology specific to the human stoned B-like proteins, and a C-terminal region homologous to the mu subunits of adaptor protein (AP) complexes. Read-through transcription of this gene into the neighboring downstream gene, which encodes TFIIA-alpha/beta-like factor, generates a transcript (SALF), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~69.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to STON1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006873.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 14 | 1 | 15 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 15 | 0 | 1 | 16 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006864.2 | 3 | MANE Select | |
| Ensembl | ENSP00000385273.1 | 3 | MANE Select | |
| RefSeq | NP_001185524.1 | 3 | Standard | |
| Ensembl | ENSP00000384615.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- Membrane Trafficking
- Clathrin-mediated endocytosis
- Cargo recognition for clathrin-mediated endocytosis
Biological Process
- endocytosis
- regulation of endocytosis
Cellular Component
- cytoplasm
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000309835
- Coding exons
- 3
- Length
- 69504
- Individuals with no LoFs
- 124658
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 157
- Defined
- 124815
- p
- 0.000629
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -2.51 | 491 | 357 | 1.37 | 0.0000172 | 4780 |
| Missense (PolyPhen) | 192 | 127.26 | 1.5087 | 1708 | ||
| Synonymous | -1.13 | 150 | 133 | 1.12 | 0.00000655 | 1395 |
| Loss of Function | 1.08 | 20 | 25.9 | 0.771 | 0.00000135 | 347 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00052 | 0.00043 | rare |
| Ashkenazi Jewish | 0.0020 | 0.0018 | notable |
| East Asian | 0.0015 | 0.0015 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00061 | 0.00061 | rare |
| South Asian | 0.00064 | 0.00062 | rare |
| Other | 0.00083 | 0.00082 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be involved in the endocytic machinery. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.104
Intolerance Scores
- LoFtool
- 0.970
- RVIS EVS
- 1.61
- RVIS percentile EVS
- 95.91
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.260
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |