SNX4
protein-codingsorting nexin 4, the group of PX-BAR domain containing|Sorting nexins|Autophagy related
Gene summary
This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein associated with the long isoform of the leptin receptor and with receptor tyrosine kinases for platelet-derived growth factor, insulin, and epidermal growth factor in cell cultures, but its function is unknown. This protein may form oligomeric complexes with family members. Two transcript variants, one protein coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Nov 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~73.6 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 SNX4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003794.4. 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 | 2 | 1 | 3 | |||
| missense | 61 | 1 | 62 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 67 | 2 | 0 | 69 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003785.1 | 14 | MANE Select | |
| Ensembl | ENSP00000251775.4 | 14 | MANE Select | |
| Ensembl | ENSP00000420175.2 | 5 | Standard | |
| Ensembl | ENSP00000420526.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- TGF_beta_Receptor
Biological Process
- protein transport
- endocytic recycling
- positive regulation of histamine secretion by mast cell
Molecular Function
- epidermal growth factor receptor binding
- insulin receptor binding
- protein binding
- phosphatidylinositol binding
- transferrin receptor binding
Cellular Component
- cytoplasm
- cytoplasmic dynein complex
- plasma membrane
- membrane
- SNARE complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000251775
- Coding exons
- 14
- Length
- 73547
- Individuals with no LoFs
- 125698
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 49
- Defined
- 125747
- p
- 0.000195
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.887 | 190 | 228 | 0.835 | 0.0000111 | 2941 |
| Missense (PolyPhen) | 39 | 49.148 | 0.79352 | 610 | ||
| Synonymous | -0.827 | 85 | 75.8 | 1.12 | 0.00000355 | 782 |
| Loss of Function | 2.45 | 17 | 31.9 | 0.533 | 0.00000190 | 358 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00027 | 0.00026 | rare |
| South Asian | 0.00026 | 0.00023 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be involved in several stages of intracellular trafficking. Plays a role in recycling endocytosed transferrin receptor and prevent its degradation. {ECO:0000269|PubMed:17994011}.;
Recessive Scores
- pRec
- 0.145
Intolerance Scores
- LoFtool
- 0.814
- RVIS EVS
- -0.58
- RVIS percentile EVS
- 18.44
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.641
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |