WIPI1
protein-codingWD repeat domain, phosphoinositide interacting 1, the group of WD repeat domain containing|WIPI family|Autophagy related
Gene summary
This gene encodes a WD40 repeat protein. Members of the WD40 repeat family are key components of many essential biologic functions. They regulate the assembly of multiprotein complexes by presenting a beta-propeller platform for simultaneous and reversible protein-protein interactions. Members of the WIPI subfamily of WD40 repeat proteins have a 7-bladed propeller structure and contain a conserved motif for interaction with phospholipids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~36.6 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 WIPI1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017983.7. 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 | 1 | 3 | ||
| missense | 61 | 1 | 1 | 63 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 68 | 2 | 2 | 72 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060453.3 | 13 | MANE Select | |
| Ensembl | ENSP00000262139.4 | 13 | MANE Select | |
| RefSeq | NP_001307701.1 | 11 | Standard | |
| Ensembl | ENSP00000437345.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Autophagy - animal - Homo sapiens (human)
- Autophagy - other - Homo sapiens (human)
- XBP1(S) activates chaperone genes
- Macroautophagy
- Cellular responses to external stimuli
Biological Process
- autophagosome assembly
- autophagy of mitochondrion
- protein lipidation
- autophagy
- cellular response to starvation
Molecular Function
- signaling receptor binding
- protein binding
- estrogen receptor binding
- phosphatidylinositol-3-phosphate binding
- androgen receptor binding
Cellular Component
- Golgi membrane
- phagophore assembly site
- autophagosome membrane
- cytoplasm
- trans-Golgi network
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262139
- Coding exons
- 13
- Length
- 36566
- Individuals with no LoFs
- 125724
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 24
- Defined
- 125748
- p
- 0.0000954
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.32 | 196 | 255 | 0.768 | 0.0000144 | 2879 |
| Missense (PolyPhen) | 65 | 81.968 | 0.793 | 912 | ||
| Synonymous | 1.28 | 87 | 104 | 0.840 | 0.00000632 | 885 |
| Loss of Function | 2.86 | 9 | 24.2 | 0.372 | 0.00000127 | 289 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays an important role in autophagy and in particular starvation- and calcium-mediated autophagy, as well as in mitophagy. Functions upstream of the ATG12-ATG5-ATG16L1 complex and LC3, and downstream of the ULK1 and PI3-kinase complexes. Involved in xenophagy of Staphylococcus aureus. Invading S.aureus cells become entrapped in autophagosome-like WIPI1 positive vesicles targeted for lysosomal degradation. Plays also a distinct role in controlling the transcription of melanogenic enzymes and melanosome maturation, a process that is distinct from starvation- induced autophagy. May also regulate the trafficking of proteins involved in the mannose-6-phosphate receptor (MPR) recycling pathway. {ECO:0000269|PubMed:15020712, ECO:0000269|PubMed:15602573, ECO:0000269|PubMed:20114074, ECO:0000269|PubMed:20484055, ECO:0000269|PubMed:20639694, ECO:0000269|PubMed:21317285, ECO:0000269|PubMed:22829830, ECO:0000269|PubMed:23088497}.;
Recessive Scores
- pRec
- 0.0945
Intolerance Scores
- LoFtool
- 0.612
- RVIS EVS
- 0.13
- RVIS percentile EVS
- 63.36
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.835
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |