WDR45

WD repeat domain 45, the group of WD repeat domain containing|WIPI family

Basic information

Region (hg38): X:49074433-49101170

Previous symbols: [ "WDRX1" ]

Links

ENSG00000196998 ∙ NCBI:11152 ∙ OMIM:300526 ∙ HGNC:28912 ∙ Uniprot:Q9Y484 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodegeneration with brain iron accumulation 5 (Strong), mode of inheritance: XL
• infantile spasms (Supportive), mode of inheritance: AD
• neurodegeneration with brain iron accumulation 5 (Moderate), mode of inheritance: XL
• neurodegeneration with brain iron accumulation 5 (Definitive), mode of inheritance: XL
• neurodegeneration with brain iron accumulation 5 (Strong), mode of inheritance: XL
• X-linked complex neurodevelopmental disorder (Definitive), mode of inheritance: XL
• neurodegeneration with brain iron accumulation 5 (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodegeneration with brain iron accumulation 5	XL	General	Genetic knowledge may potentially be beneficial related to manifestations such as renal issues; 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	21920862; 22892189; 23176820; 23435086; 23447832; 23687123

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WDR45 gene.

• Neurodegeneration_with_brain_iron_accumulation_5 (438 variants)
• not_provided (142 variants)
• Inborn_genetic_diseases (42 variants)
• not_specified (35 variants)
• WDR45-related_disorder (9 variants)
• Intellectual_disability (6 variants)
• Oculocutaneous_albinism_type_7 (4 variants)
• Global_developmental_delay (4 variants)
• X-linked_cerebral-cerebellar-coloboma_syndrome_syndrome (3 variants)
• Seizure (3 variants)
• See_cases (2 variants)
• Optic_atrophy_2 (2 variants)
• Basal_ganglia_calcification (1 variants)
• Dystonic_disorder (1 variants)
• Delayed_gross_motor_development (1 variants)
• Migraine,_familial_hemiplegic,_1 (1 variants)
• Delayed_speech_and_language_development (1 variants)
• Autism (1 variants)
• Hypoplasia_of_the_corpus_callosum (1 variants)
• Neurodegeneration_with_brain_iron_accumulation (1 variants)
• Absent_speech (1 variants)
• Developmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WDR45 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001029896.2. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		3	62	4	70
missense	4	28	109	38	3	182
nonsense	24	3	1			28
start loss	2	2				4
frameshift	62	17	4			83
splice donor/acceptor (+/-2bp)	27	19				46
Total	120	69	117	100	7

Highest pathogenic variant AF is 0.00000638512

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WDR45	protein_coding	protein_coding	ENST00000356463	10	28724

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.991	0.00854	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.02	92	165	0.558	0.0000145	2373
Missense in Polyphen		11	32.817	0.33519		529
Synonymous	1.78	47	65.3	0.719	0.00000582	715
Loss of Function	3.50	0	14.3	0.00	0.00000119	205

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays an important role in the autophagy pathway, which is the major intracellular degradation system by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation. {ECO:0000269|PubMed:23435086}.
• Pathway: Macroautophagy;Cellular responses to external stimuli (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.379
• rvis_EVS: -0.27
• rvis_percentile_EVS: 33.97

Haploinsufficiency Scores

• pHI: 0.274
• hipred: N
• hipred_score: 0.489
• ghis: 0.467

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.925

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wdr45

Gene ontology

• Biological process: autophagosome assembly;autophagy of mitochondrion;protein lipidation;autophagy;cellular response to starvation;protein localization to phagophore assembly site
• Cellular component: phagophore assembly site;cytosol;extrinsic component of membrane;phagophore assembly site membrane
• Molecular function: protein binding;protein kinase binding;phosphatidylinositol-3-phosphate binding;phosphatidylinositol-3,5-bisphosphate binding;phosphatidylinositol phosphate binding