WDR45

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

Basic information

Region (hg38): X:49074432-49101170

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
• West syndrome (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

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 (326 variants)
• not provided (114 variants)
• not specified (34 variants)
• Inborn genetic diseases (32 variants)
• Intellectual disability (5 variants)
• X-linked cerebral-cerebellar-coloboma syndrome syndrome (3 variants)
• WDR45-related condition (3 variants)
• Global developmental delay (2 variants)
• See cases (2 variants)
• Neurodegeneration with brain iron accumulation (1 variants)
• Migraine, familial hemiplegic, 1 (1 variants)
• Developmental disorder (1 variants)
• Neurodegeneration with brain iron accumulation 5;Oculocutaneous albinism type 7 (1 variants)
• Oculocutaneous albinism type 7;Neurodegeneration with brain iron accumulation 5 (1 variants)
• 6 conditions (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.

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				44	4	48
missense	3	11	84	26	1	125
nonsense	19	3				22
start loss	2	1				3
frameshift	47	9	2			58
inframe indel		4	4			8
splice donor/acceptor (+/-2bp)	22	11	1			34
splice region		8	9	17	2	36
non coding	1	1	3	44	18	67
Total	94	40	94	114	23

Variants in WDR45

This is a list of pathogenic ClinVar variants found in the WDR45 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-49074784-A-T		not specified	Likely benign (Sep 02, 2017)
X-49074809-GTCA-G		Neurodegeneration with brain iron accumulation 5	Uncertain significance (Aug 31, 2022)
X-49074821-AC-A		Neurodegeneration with brain iron accumulation 5	Uncertain significance (Dec 11, 2023)
X-49074823-A-C		Neurodegeneration with brain iron accumulation 5	Uncertain significance (Aug 10, 2023)
X-49074824-G-T		Neurodegeneration with brain iron accumulation 5	Likely benign (Sep 23, 2022)
X-49074835-A-G		Neurodegeneration with brain iron accumulation 5	Likely benign (Aug 30, 2023)
X-49074838-C-T		Neurodegeneration with brain iron accumulation 5	Uncertain significance (May 22, 2023)
X-49074841-C-T		Neurodegeneration with brain iron accumulation 5 • Inborn genetic diseases	Uncertain significance (Jan 19, 2024)
X-49074847-C-A		Neurodegeneration with brain iron accumulation 5	Likely benign (Feb 09, 2022)
X-49074847-CCT-C		Neurodegeneration with brain iron accumulation 5	Pathogenic (Jun 13, 2022)
X-49074850-C-A		Neurodegeneration with brain iron accumulation 5	Pathogenic (Oct 28, 2022)
X-49074856-T-C		Neurodegeneration with brain iron accumulation 5	Likely pathogenic (Feb 13, 2015)
X-49074856-T-TG		Neurodegeneration with brain iron accumulation 5	Pathogenic (Oct 02, 2020)
X-49074858-CA-C		Neurodegeneration with brain iron accumulation 5	Likely pathogenic (May 21, 2019)
X-49074865-C-T		Neurodegeneration with brain iron accumulation 5	Uncertain significance (Nov 15, 2022)
X-49074869-A-G		Neurodegeneration with brain iron accumulation 5	Likely benign (Mar 29, 2023)
X-49074874-T-C		Neurodegeneration with brain iron accumulation 5	Uncertain significance (Mar 04, 2023)
X-49074874-TGA-T		Neurodegeneration with brain iron accumulation 5	Pathogenic (Aug 09, 2022)
X-49074880-CAT-C		Neurodegeneration with brain iron accumulation 5 • See cases	Pathogenic (Jun 04, 2023)
X-49074881-A-C		Neurodegeneration with brain iron accumulation 5	Pathogenic (Sep 21, 2019)
X-49074881-A-T		Neurodegeneration with brain iron accumulation 5	Pathogenic (Feb 03, 2022)
X-49074887-G-C		WDR45-related disorder	Uncertain significance (Jan 19, 2023)
X-49074898-C-T		Migraine, familial hemiplegic, 1	Uncertain significance (Jun 13, 2023)
X-49074902-TAC-CAA		Neurodegeneration with brain iron accumulation 5	Likely benign (Jan 01, 2019)
X-49074903-A-G		Inborn genetic diseases	Uncertain significance (Sep 14, 2021)

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