WDR45B

protein-coding

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

Gene summary

This gene encodes a member of the WIPI or SVP1 family of WD40 repeat-containing proteins. The protein contains seven WD40 repeats that are thought to fold into a beta-propeller structure that mediates protein-protein interactions, and a conserved motif for interaction with phospholipids. The human genome contains several pseudogenes of this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

WDR45L

MANE transcript

NM_019613.4

Inheritance

ClinVar variants

P:3U:38B:14

Top phenotype

Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr17:82,614,562-82,648,553

External References & Databases

Ensembl (ENSG00000141580)

Transcript & Mutation Effects

hg38 • Region Span ~34.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0060704

Submitter: PanelApp Australia

neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0060704

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizuresSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0060704

Submitter: Baylor College of Medicine Research Center

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizuresAR

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 21937992; 28503735

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WDR45B variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 29

not providedTotal: 13

not specifiedTotal: 10

Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizuresTotal: 7

WDR45B-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019613.4. 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			1 clinvar	11 clinvar	1 clinvar	13
missense			32 clinvar	2 clinvar		34
nonsense	1 clinvar	2 clinvar				3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	1	2	38	13	1	55

Highest pathogenic variant AF is 0.0000037177347

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 56 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_019613.4	RefSeq	NP_062559.2	10	MANE Select
ENST00000392325.9	Ensembl	ENSP00000376139.4	10	MANE Select
ENST00000571817.5	Ensembl	ENSP00000461355.1	4	Standard
ENST00000572583.5	Ensembl	ENSP00000461488.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Macroautophagy
Cellular responses to external stimuli

Biological Process

autophagosome assembly
autophagy of mitochondrion
protein lipidation
cellular response to starvation
protein localization to phagophore assembly site

Molecular Function

protein binding
phosphatidylinositol-3-phosphate binding
TSC1-TSC2 complex binding
phosphatidylinositol-3,5-bisphosphate binding

Cellular Component

phagophore assembly site
lysosome
cytosol
extrinsic component of membrane
phagophore assembly site membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392325
Coding exons: 10
Length: 33992
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125748
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.01	150	189	0.793	0.0000112	2268
Missense (PolyPhen)		18	39.426	0.45655		471
Synonymous	-0.863	88	78.3	1.12	0.00000558	646
Loss of Function	2.99	5	19.1	0.262	0.00000110	225

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.118

Intolerance Scores

RVIS EVS: -0.25
RVIS percentile EVS: 35.99

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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