WIPI2

WD repeat domain, phosphoinositide interacting 2, the group of WD repeat domain containing|WIPI family|Autophagy related

Basic information

Region (hg38): 7:5190196-5233840

Links

ENSG00000157954 ∙ NCBI:26100 ∙ OMIM:609225 ∙ HGNC:32225 ∙ Uniprot:Q9Y4P8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder with short stature and variable skeletal anomalies (Limited), mode of inheritance: AR
• intellectual developmental disorder with short stature and variable skeletal anomalies (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with short stature and variable skeletal anomalies	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic; Musculoskeletal	30968111

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WIPI2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WIPI2 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				7	7	14
missense			13	1	2	16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region					2	2
non coding				1	1	2
Total	0	0	14	9	10

Variants in WIPI2

This is a list of pathogenic ClinVar variants found in the WIPI2 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-5190495-T-G		Intellectual developmental disorder with short stature and variable skeletal anomalies	Uncertain significance (Feb 14, 2023)
7-5193119-G-A		not specified	Uncertain significance (Aug 10, 2021)
7-5193178-T-G		WIPI2-related disorder	Benign (Dec 02, 2019)
7-5199601-G-T		not specified	Uncertain significance (Apr 29, 2024)
7-5199650-A-C		not specified	Uncertain significance (Jan 19, 2024)
7-5199653-A-C		not specified	Uncertain significance (May 20, 2024)
7-5214587-G-A		WIPI2-related disorder	Benign (Oct 29, 2019)
7-5214596-C-G		WIPI2-related disorder	Benign (Nov 05, 2019)
7-5214667-A-G		not specified	Uncertain significance (Jul 17, 2023)
7-5216554-C-T		WIPI2-related disorder	Benign (Dec 31, 2019)
7-5216578-C-T		WIPI2-related disorder	Likely benign (Apr 01, 2023)
7-5216642-C-T		not specified	Uncertain significance (Oct 10, 2023)
7-5217146-G-A		not specified	Uncertain significance (Aug 16, 2021)
7-5217162-T-G		Intellectual developmental disorder with short stature and variable skeletal anomalies	Pathogenic (Nov 11, 2021)
7-5217942-G-A		WIPI2-related disorder	Benign (Dec 03, 2019)
7-5217969-G-A		WIPI2-related disorder	Benign (Jun 05, 2018)
7-5222656-C-T		Intellectual developmental disorder with short stature and variable skeletal anomalies	Uncertain significance (May 05, 2020)
7-5225827-G-A		Intellectual developmental disorder with short stature and variable skeletal anomalies	Pathogenic (Nov 02, 2021)
7-5225860-G-A		WIPI2-related disorder	Benign (Jan 14, 2020)
7-5225871-C-T		WIPI2-related disorder	Likely benign (Feb 01, 2024)
7-5225913-C-T			Likely benign (Apr 01, 2024)
7-5227275-A-G		not specified	Uncertain significance (Jun 23, 2023)
7-5227297-G-A			Likely benign (Feb 01, 2023)
7-5227327-C-T		WIPI2-related disorder	Benign (Dec 31, 2019)
7-5228095-T-G			Likely benign (May 31, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WIPI2	protein_coding	protein_coding	ENST00000288828	13	43639

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00639	0.993	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.66	204	283	0.722	0.0000178	2951
Missense in Polyphen		19	48.848	0.38896		540
Synonymous	-0.986	140	126	1.11	0.00000958	893
Loss of Function	2.94	8	23.3	0.343	0.00000109	283

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000149	0.000149
Ashkenazi Jewish	0.00	0.00
East Asian	0.000110	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000620	0.0000615
Middle Eastern	0.000110	0.000109
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Early component of the autophagy machinery being involved in formation of preautophagosomal structures and their maturation into mature phagosomes in response to phosphatidylinositol 3-phosphate (PtdIns3P). May bind PtdIns3P. {ECO:0000269|PubMed:20505359}.
• Pathway: Autophagy - animal - Homo sapiens (human);Autophagy - other - Homo sapiens (human);Macroautophagy;Cellular responses to external stimuli (Consensus)

Recessive Scores

• pRec: 0.0854

Intolerance Scores

• loftool: 0.636
• rvis_EVS: -1.07
• rvis_percentile_EVS: 7.43

Haploinsufficiency Scores

• pHI: 0.100
• hipred: Y
• hipred_score: 0.639
• ghis: 0.558

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.928

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wipi2

Gene ontology

• Biological process: autophagosome assembly;autophagy of mitochondrion;protein lipidation;cellular response to starvation;macroautophagy;protein localization to phagophore assembly site;protein lipidation involved in autophagosome assembly;autophagosome maturation;xenophagy
• Cellular component: phagophore assembly site;nucleoplasm;autophagosome;cytosol;membrane;extrinsic component of membrane;protein-containing complex;phagophore assembly site membrane
• Molecular function: protein binding;phosphatidylinositol-3-phosphate binding;phosphatidylinositol-3,5-bisphosphate binding