SNX9
protein-codingsorting nexin 9, the group of PX-BAR domain containing|Sorting nexins
Gene summary
This gene encodes a member of the sorting nexin family. Members of this family contain a phosphoinositide binding domain, and are involved in intracellular trafficking. The encoded protein does not contain a coiled coil region, like some family members, but does contain a SRC homology domain near its N-terminus. The encoded protein is reported to have a variety of interaction partners, including of adaptor protein 2 , dynamin, tyrosine kinase non-receptor 2, Wiskott-Aldrich syndrome-like, and ARP3 actin-related protein 3. The encoded protein is implicated in several stages of intracellular trafficking, including endocytosis, macropinocytosis, and F-actin nucleation. [provided by RefSeq, Jul 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~244.7 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 SNX9 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016224.5. 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 | 5 | 1 | 6 | |||
| missense | 50 | 2 | 52 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 58 | 3 | 0 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057308.1 | 18 | MANE Select | |
| Ensembl | ENSP00000376024.3 | 18 | MANE Select | |
| Ensembl | ENSP00000482920.1 | 3 | Standard | |
| Ensembl | ENSP00000479382.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- EGF-Ncore
- Golgi Associated Vesicle Biogenesis
- Clathrin derived vesicle budding
- trans-Golgi Network Vesicle Budding
- Vesicle-mediated transport
Biological Process
- mitotic cytokinesis
- intracellular protein transport
- endocytosis
- receptor-mediated endocytosis
- endosomal transport
Molecular Function
- protein binding
- 1-phosphatidylinositol binding
- ubiquitin protein ligase binding
- phosphatidylinositol binding
- identical protein binding
Cellular Component
- ruffle
- cytoplasm
- trans-Golgi network
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000392185
- Coding exons
- 18
- Length
- 121814
- Individuals with no LoFs
- 125720
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 28
- Defined
- 125748
- p
- 0.000111
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.82 | 237 | 330 | 0.718 | 0.0000178 | 3939 |
| Missense (PolyPhen) | 97 | 161.36 | 0.60116 | 1952 | ||
| Synonymous | 1.42 | 96 | 115 | 0.832 | 0.00000666 | 1057 |
| Loss of Function | 4.62 | 8 | 39.2 | 0.204 | 0.00000199 | 456 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000033 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00046 | 0.00046 | rare |
| European (Non-Finnish) | 0.00015 | 0.00013 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in endocytosis and intracellular vesicle trafficking, both during interphase and at the end of mitosis. Required for efficient progress through mitosis and cytokinesis. Required for normal formation of the cleavage furrow at the end of mitosis. Plays a role in endocytosis via clathrin-coated pits, but also clathrin-independent, actin-dependent fluid-phase endocytosis. Plays a role in macropinocytosis. Promotes internalization of TNFR. Promotes degradation of EGFR after EGF signaling. Stimulates the GTPase activity of DNM1. Promotes DNM1 oligomerization. Promotes activation of the Arp2/3 complex by WASL, and thereby plays a role in the reorganization of the F- actin cytoskeleton. Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate and promotes membrane tubulation. Has lower affinity for membranes enriched in phosphatidylinositol 3-phosphate. {ECO:0000269|PubMed:11799118, ECO:0000269|PubMed:12952949, ECO:0000269|PubMed:15703209, ECO:0000269|PubMed:17609109, ECO:0000269|PubMed:17948057, ECO:0000269|PubMed:18388313, ECO:0000269|PubMed:20427313, ECO:0000269|PubMed:21048941, ECO:0000269|PubMed:22718350}.;
Recessive Scores
- pRec
- 0.180
Intolerance Scores
- LoFtool
- 0.737
- RVIS EVS
- -0.13
- RVIS percentile EVS
- 43.91
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.974
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |