WDR1

protein-coding

WD repeat domain 1, the group of MicroRNA protein coding host genes|WD repeat domain containing

Gene summary

This gene encodes a protein containing 9 WD repeats. WD repeats are approximately 30- to 40-amino acid domains containing several conserved residues, mostly including a trp-asp at the C-terminal end. WD domains are involved in protein-protein interactions. The encoded protein may help induce the disassembly of actin filaments. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_017491.5

Inheritance

ClinVar variants

P:5U:177B:226

Top phenotype

periodic fever, immunodeficiency, and thrombocytopenia syndrome

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr4:10,068,089-10,116,972

External References & Databases

Ensembl (ENSG00000071127)

Transcript & Mutation Effects

hg38 • Region Span ~48.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

periodic fever, immunodeficiency, and thrombocytopenia syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0007883

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WDR1 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 516

not specifiedTotal: 91

Inborn genetic diseasesTotal: 66

WDR1-related disorderTotal: 31

Lazy leukocyte syndromeTotal: 15

WDR1 deficiencyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017491.5. 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			5 clinvar	215 clinvar		220
missense	5 clinvar		163 clinvar	11 clinvar		179
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	5	0	177	226	0	408

Highest pathogenic variant AF is 0.0000020532307

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 60 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017491.5	RefSeq	NP_059830.1	15	MANE Select
ENST00000499869.7	Ensembl	ENSP00000427687.1	15	MANE Select
NM_005112.5	RefSeq	NP_005103.2	12	Standard
ENST00000264785.12	Ensembl	ENSP00000514597.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
wdr1	Danio rerio	Structure: mandibular arch skeleton Quality: protruding abnormal

Gene / Model

Organism

Observed Phenotype

wdr1

Danio rerio

Structure: mandibular arch skeleton

Quality: protruding

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Hypertrophy Model
TCR
Platelet degranulation
Response to elevated platelet cytosolic Ca2+
Platelet activation, signaling and aggregation

Biological Process

neutrophil mediated immunity
platelet degranulation
sensory perception of sound
regulation of cell shape
actin filament depolymerization

Molecular Function

actin filament binding

Cellular Component

podosome
extracellular region
cytosol
plasma membrane
cell-cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000499869
Coding exons: 15
Length: 42611
Individuals with no LoFs: 124626
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 124628
p: 0.00000802

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.93	275	381	0.721	0.0000240	3967
Missense (PolyPhen)		71	142.62	0.49782		1569
Synonymous	-2.45	215	174	1.24	0.0000137	1149
Loss of Function	4.61	2	28.6	0.0699	0.00000131	342

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Induces disassembly of actin filaments in conjunction with ADF/cofilin family proteins (PubMed:15629458). Enhances cofilin-mediated actin severing (By similarity). Involved in cytokinesis. Involved in chemotactic cell migration by restricting lamellipodial membrane protrusions (PubMed:18494608). Involved in myocardium sarcomere organization. Required for cardiomyocyte growth and maintenance (By similarity). Involved in megakaryocyte maturation and platelet shedding. Required for the establishment of planar cell polarity (PCP) during follicular epithelium development and for cell shape changes during PCP; the function seems to implicate cooperation with CFL1 and/or DSTN/ADF. Involved in the generation/maintenance of cortical tension (By similarity). Involved in assembly and maintenance of epithelial apical cell junctions and plays a role in the organization of the perijunctional actomyosin belt (PubMed:25792565). {ECO:0000250|UniProtKB:O88342, ECO:0000250|UniProtKB:Q9W7F2, ECO:0000269|PubMed:15629458, ECO:0000269|PubMed:18494608, ECO:0000269|PubMed:25792565}.;

Recessive Scores

pRec: 0.138

Intolerance Scores

RVIS EVS: -0.57
RVIS percentile EVS: 18.9

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Indispensability pred.: E
Indispensability score: 0.944

Gene Damage Prediction

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