WDR45 WD repeat domain 45 [Homo sapiens (human)] - Gene

Summary

Official Symbol: WDR45provided by HGNC
Official Full Name: WD repeat domain 45provided by HGNC
Primary source: HGNC:HGNC:28912
See related: Ensembl:ENSG00000196998 MIM:300526; AllianceGenome:HGNC:28912
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: JM5; NBIA4; NBIA5; WDRX1; WIPI4; WIPI-4
Summary: This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene has a pseudogene at chromosome 4q31.3. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity and full-length nature of some variants have not been determined. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in thyroid (RPKM 16.7), adrenal (RPKM 15.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xp11.23

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (49074442..49101178, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (48486169..48512926, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (48932101..48958116, complement)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Variants in the WDR45 Gene Within the OPA-2 Locus Associate With Isolated X-Linked Optic Atrophy.
Title: Variants in the WDR45 Gene Within the OPA-2 Locus Associate With Isolated X-Linked Optic Atrophy.
WDR45 mutation dysregulates iron homeostasis by promoting the chaperone-mediated autophagic degradation of ferritin heavy chain in an ER stress/p38 dependent mechanism.
Title: WDR45 mutation dysregulates iron homeostasis by promoting the chaperone-mediated autophagic degradation of ferritin heavy chain in an ER stress/p38 dependent mechanism.
Quantitative retrospective natural history modeling of WDR45-related developmental and epileptic encephalopathy - a systematic cross-sectional analysis of 160 published cases.
Title: Quantitative retrospective natural history modeling of WDR45-related developmental and epileptic encephalopathy - a systematic cross-sectional analysis of 160 published cases.
Autophagic defects observed in fibroblasts from a patient with beta-propeller protein-associated neurodegeneration.
Title: Autophagic defects observed in fibroblasts from a patient with β-propeller protein-associated neurodegeneration.
A neurodegeneration gene, WDR45, links impaired ferritinophagy to iron accumulation.
Title: A neurodegeneration gene, WDR45, links impaired ferritinophagy to iron accumulation.
Iron Accumulation and Changes in Cellular Organelles in WDR45 Mutant Fibroblasts.
Title: Iron Accumulation and Changes in Cellular Organelles in WDR45 Mutant Fibroblasts.
Beta-propeller protein-associated neurodegeneration presenting Rett-like features: A case report and literature review.
Title: Beta-propeller protein-associated neurodegeneration presenting Rett-like features: A case report and literature review.
Phenotypic and Imaging Spectrum Associated With WDR45.
Title: Phenotypic and Imaging Spectrum Associated With WDR45.
De novo variants in WDR45 underlie beta-propeller protein-associated neurodegeneration in five independent families.
Title: De novo variants in WDR45 underlie beta-propeller protein-associated neurodegeneration in five independent families.
Beta-propeller protein-associated neurodegeneration (BPAN, OMIM 300894) is an X-linked neurodegenerative disorder caused by mutations in WDR45. Novel mutation in WDR45 impaired autophagy in cells thus this mutation is the cause for BPAN in this patient.
Title: Functional evidence for a de novo mutation in WDR45 leading to BPAN in a Chinese girl.

Submit: New GeneRIF Correction See all GeneRIFs (28)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Neurodegeneration with brain iron accumulation 5 MedGen: C3550973 OMIM: 300894 GeneReviews: Neurodegeneration with Brain Iron Accumulation Disorders Overview, Beta-Propeller Protein-Associated Neurodegeneration	Compare labs
Oculocutaneous albinism type 7 MedGen: C3808786 OMIM: 615179 GeneReviews: Oculocutaneous Albinism and Ocular Albinism Overview	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2015-04-09) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2015-04-09) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

MARC_10039-10040:997207294:1 (e-PCR)
- UniSTS:267023

L18426 (e-PCR)
- UniSTS:34648

DXS8228 (e-PCR)
- UniSTS:25022

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables phosphatidylinositol phosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol-3,5-bisphosphate binding	IBA Inferred from Biological aspect of Ancestor more info
enables phosphatidylinositol-3-phosphate binding	IBA Inferred from Biological aspect of Ancestor more info
enables phosphatidylinositol-3-phosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in autophagosome assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in autophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in autophagy of mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
involved_in autophagy of peroxisome	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to starvation	IDA Inferred from Direct Assay more info	PubMed
involved_in glycophagy	IBA Inferred from Biological aspect of Ancestor more info
involved_in nucleophagy	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of autophagosome assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in protein lipidation	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein localization to phagophore assembly site	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
is_active_in extrinsic component of membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in phagophore assembly site	IDA Inferred from Direct Assay more info	PubMed
is_active_in phagophore assembly site membrane	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: WD repeat domain phosphoinositide-interacting protein 4

Names: WD repeat domain, X-linked 1; WD repeat-containing protein 45; WD45 repeat protein interacting with phosphoinositides 4; neurodegeneration with brain iron accumulation 4; neurodegeneration with brain iron accumulation 5

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_033004.2 RefSeqGene

Range

26284..31729

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001029896.2 → NP_001025067.1 WD repeat domain phosphoinositide-interacting protein 4 isoform 2

See identical proteins and their annotated locations for NP_001025067.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) has an alternate 5' UTR and lacks a 3-nt segment in the CDS, as compared to variant 1. The encoded isoform 2 thus lacks an internal amino acid, as compared to isoform 1.

Source sequence(s)

AJ005897, BC035979, BQ068083

Consensus CDS

CCDS35250.1

UniProtKB/Swiss-Prot

A6NGH5, B7WPI2, Q5MNZ5, Q6IBS7, Q6NT94, Q96H03, Q9Y484

UniProtKB/TrEMBL

A0A0U1RR06

Related

ENSP00000365551.3, ENST00000376372.9

Conserved Domains (2) summary

sd00039
Location:196 → 232

7WD40; WD40 repeat [structural motif]

cl29593
Location:187 → 274

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
NM_007075.4 → NP_009006.2 WD repeat domain phosphoinositide-interacting protein 4 isoform 1

See identical proteins and their annotated locations for NP_009006.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents a longer transcript and encodes a longer isoform (1).

Source sequence(s)

AC231657, AF196779, BC035979, BC069206

Consensus CDS

CCDS14318.1

UniProtKB/TrEMBL

A0A0U1RR06

Related

ENSP00000348848.3, ENST00000356463.7

Conserved Domains (2) summary

sd00039
Location:197 → 233

7WD40; WD40 repeat [structural motif]

cl29593
Location:8 → 265

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...