WIPI2

protein-coding

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

Gene summary

WD40 repeat proteins 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, such as WIPI2, have a 7-bladed propeller structure and contain a conserved motif for interaction with phospholipids (Proikas-Cezanne et al., 2004 [PubMed 15602573]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_015610.4

Inheritance

ClinVar variants

P:2U:62B:28

Top phenotype

Intellectual developmental disorder with short stature and variable skeletal anomalies

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr7:5,190,196-5,233,840

External References & Databases

Ensembl (ENSG00000157954)

Transcript & Mutation Effects

hg38 • Region Span ~43.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder with short stature and variable skeletal anomaliesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032759

Submitter: PanelApp Australia

intellectual developmental disorder with short stature and variable skeletal anomaliesLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032759

Submitter: Labcorp Genetics (formerly Invitae)

intellectual developmental disorder with short stature and variable skeletal anomaliesMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032759

Submitter: G2P

intellectual developmental disorder with short stature and variable skeletal anomaliesLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032759

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Intellectual developmental disorder with short stature and variable skeletal anomaliesAR

Manifestation: Neurologic; Musculoskeletal

Intervention: General

Rationale: 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

Refs: 30968111

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WIPI2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 60

not providedTotal: 20

WIPI2-related disorderTotal: 13

Intellectual developmental disorder with short stature and variable skeletal anomaliesTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015610.4. 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 clinvar	16 clinvar	5 clinvar	23
missense	2 clinvar		55 clinvar	5 clinvar	2 clinvar	64
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	2	0	62	21	7	92

Highest pathogenic variant AF is 0.000004965243

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015610.4	RefSeq	NP_056425.1	13	MANE Select
ENST00000288828.9	Ensembl	ENSP00000288828.4	13	MANE Select
NM_001033518.2	RefSeq	NP_001028690.1	13	Standard
NM_001033519.2	RefSeq	NP_001028691.1	12	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)
Macroautophagy
Cellular responses to external stimuli

Biological Process

autophagosome assembly
autophagy of mitochondrion
protein lipidation
cellular response to starvation
macroautophagy

Molecular Function

protein binding
phosphatidylinositol-3-phosphate binding
phosphatidylinositol-3,5-bisphosphate binding

Cellular Component

phagophore assembly site
nucleoplasm
autophagosome
cytosol
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000288828
Coding exons: 13
Length: 43639
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.66	204	283	0.722	0.0000178	2951
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.0854

Intolerance Scores

LoFtool: 0.636
RVIS EVS: -1.07
RVIS percentile EVS: 7.43

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.928

Gene Damage Prediction

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