WIPI1

WD repeat domain, phosphoinositide interacting 1, the group of WD repeat domain containing|WIPI family|Autophagy related

Basic information

Region (hg38): 17:68420947-68457513

Links

ENSG00000070540 ∙ NCBI:55062 ∙ OMIM:609224 ∙ HGNC:25471 ∙ Uniprot:Q5MNZ9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WIPI1 gene.

• Inborn genetic diseases (15 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WIPI1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			15		1	16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	15	0	2

Variants in WIPI1

This is a list of pathogenic ClinVar variants found in the WIPI1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-68421792-C-T		not specified	Uncertain significance (Oct 27, 2023)
17-68426148-C-T		not specified	Uncertain significance (Aug 14, 2023)
17-68426154-G-A		not specified	Uncertain significance (Apr 26, 2023)
17-68427131-C-T			Benign (Jun 10, 2018)
17-68427143-G-A		not specified	Uncertain significance (Mar 29, 2023)
17-68427175-G-A		WIPI1-related disorder	Likely benign (Feb 23, 2021)
17-68427233-G-C		not specified	Uncertain significance (Dec 13, 2023)
17-68428833-G-A		not specified	Uncertain significance (Nov 17, 2022)
17-68428856-C-T		not specified	Uncertain significance (Jun 30, 2022)
17-68428919-C-T		Neural tube defect	Affects (-)
17-68430011-A-T		not specified	Uncertain significance (May 05, 2023)
17-68430038-C-T			Benign (Jun 21, 2018)
17-68430039-G-A		not specified	Uncertain significance (Jun 03, 2022)
17-68430044-G-A		not specified	Uncertain significance (Oct 20, 2021)
17-68430114-A-G		not specified	Uncertain significance (Jun 23, 2023)
17-68430129-A-T		not specified	Uncertain significance (Nov 10, 2022)
17-68433475-T-C		not specified	Uncertain significance (Jul 08, 2022)
17-68433508-C-T		not specified	Uncertain significance (Sep 01, 2021)
17-68434561-C-T		WIPI1-related disorder	Likely benign (Apr 28, 2022)
17-68434599-G-C		not specified	Uncertain significance (Sep 14, 2021)
17-68435625-C-T		not specified	Uncertain significance (Mar 29, 2022)
17-68435685-C-T		not specified	Uncertain significance (Oct 13, 2023)
17-68436437-G-A		not specified	Uncertain significance (Apr 27, 2023)
17-68450824-T-C			Benign (Jun 10, 2018)
17-68450874-C-T		not specified	Uncertain significance (Dec 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WIPI1	protein_coding	protein_coding	ENST00000262139	13	36566

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00170	0.997	125724	0	24	125748	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.32	196	255	0.768	0.0000144	2879
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000114	0.000114
Middle Eastern	0.000272	0.000272
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Autophagy - animal - Homo sapiens (human);Autophagy - other - Homo sapiens (human);XBP1(S) activates chaperone genes;Macroautophagy;Cellular responses to external stimuli (Consensus)

Recessive Scores

• pRec: 0.0945

Intolerance Scores

• loftool: 0.612
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63.36

Haploinsufficiency Scores

• pHI: 0.242
• hipred: Y
• hipred_score: 0.605
• ghis: 0.416

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.835

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Wipi1

Gene ontology

• Biological process: autophagosome assembly;autophagy of mitochondrion;protein lipidation;autophagy;cellular response to starvation;macroautophagy;protein localization to phagophore assembly site;IRE1-mediated unfolded protein response;vesicle targeting, trans-Golgi to endosome
• Cellular component: Golgi membrane;phagophore assembly site;autophagosome membrane;cytoplasm;trans-Golgi network;cytosol;cytoskeleton;endosome membrane;extrinsic component of membrane;clathrin-coated vesicle;phagophore assembly site membrane
• Molecular function: signaling receptor binding;protein binding;estrogen receptor binding;phosphatidylinositol-3-phosphate binding;androgen receptor binding;phosphatidylinositol-3,5-bisphosphate binding