WDR73

protein-coding

WD repeat domain 73, the group of WD repeat domain containing

Gene summary

The protein encoded by this gene is thought to contain multiple WD40 repeats. WD40 repeats are motifs that contain 40-60 amino acids, and usually end with Trp-Asp (WD). This protein is found in the cytoplasm during interphase, but accumulates at the spindle poles and astral microtubules during mitosis. Reduced expression of this gene results in abnormalities in the size and morphology of the nucleus. Mutations in this gene have been associated with Galloway-Mowat syndrome PMID: 25466283), which is a rare autosomal recessive disorder that affects both the central nervous system and kidneys. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

MANE transcript

NM_032856.5

Inheritance

ClinVar variants

P:43U:135B:50

Top phenotype

Galloway-Mowat syndrome 1

gnomAD constraint

pLI —, LoF o/e 0.82

Max pathogenic AF

—

Genomic locus

chr15:84,639,285-84,654,343

External References & Databases

Ensembl (ENSG00000177082)

Transcript & Mutation Effects

hg38 • Region Span ~15.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Galloway-Mowat syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009627

Submitter: Orphanet

Galloway-Mowat syndrome 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033005

Submitter: PanelApp Australia

Galloway-Mowat syndrome 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033005

Submitter: Labcorp Genetics (formerly Invitae)

CAMOS syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019374

Submitter: Orphanet

Galloway-Mowat syndrome 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033005

Submitter: G2P

Clinical Genomic Database (CGD)

Galloway-Mowat syndrome 1AR

Manifestation: Neurologic; Renal

Intervention: General

Rationale: 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: 25466283; 25873735; 26123727

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WDR73 variants in ClinVar

11 Conditions Cataloged

not providedTotal: 152

Galloway-Mowat syndrome 1Total: 123

Inborn genetic diseasesTotal: 62

not specifiedTotal: 19

WDR73-related disorderTotal: 18

Nephrotic syndromeTotal: 3

Abnormality of the nervous systemTotal: 1

Dystonic disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032856.5. 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			3 clinvar	36 clinvar	1 clinvar	40
missense	1 clinvar	6 clinvar	126 clinvar	11 clinvar	1 clinvar	145
nonsense	6 clinvar	9 clinvar	2 clinvar			17
start loss			1 clinvar			1
frameshift	8 clinvar	10 clinvar	2 clinvar	1 clinvar		21
splice donor/acceptor (+/-2bp)	2 clinvar	1 clinvar	1 clinvar			4
Total	17	26	135	48	2	228

Highest pathogenic variant AF is 0.00005762603

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032856.5	RefSeq	NP_116245.2	8	MANE Select
ENST00000434634.7	Ensembl	ENSP00000387982.3	8	MANE Select
ENST00000558521.5	Ensembl	ENSP00000453732.1	7	Standard
ENST00000559178.5	Ensembl	ENSP00000453204.1	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
wdr73	Danio rerio	Structure: ventricular system Quality: dilated abnormal

Gene / Model

Organism

Observed Phenotype

wdr73

Danio rerio

Structure: ventricular system

Quality: dilated

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

nucleus organization
cytoplasmic microtubule organization
negative regulation of apoptotic process

Molecular Function

molecular_function

Cellular Component

spindle pole
cytosol
cleavage furrow

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000434634
Coding exons: 8
Length: 11576
Individuals with no LoFs: 124577
Homozygous LoFs: 0
Heterozygous LoFs: 69
Defined: 124646
p: 0.000277

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.461	225	206	1.09	0.0000110	2388
Missense (PolyPhen)		62	68.123	0.91011		844
Synonymous	0.128	76	77.4	0.981	0.00000391	758
Loss of Function	0.722	15	18.3	0.818	9.94e-7	204

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00061	0.00061	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00027	0.00027	rare
South Asian	0.00070	0.00069	rare
Other	0.00017	0.00017	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in the regulation of microtubule organization and dynamics (PubMed:25466283). {ECO:0000269|PubMed:25466283}.;
Disease: DISEASE: Galloway-Mowat syndrome 1 (GAMOS1) [MIM:251300]: A form of Galloway-Mowat syndrome, a severe renal-neurological disease characterized by early-onset nephrotic syndrome associated with microcephaly, central nervous system abnormalities, developmental delays, and a propensity for seizures. Brain anomalies include gyration defects ranging from lissencephaly to pachygyria and polymicrogyria, and cerebellar hypoplasia. Most patients show facial dysmorphism characterized by a small, narrow forehead, large/floppy ears, deep-set eyes, hypertelorism and micrognathia. Additional variable features are visual impairment and arachnodactyly. Patients may die in early childhood. GAMOS1 inheritance is autosomal recessive. {ECO:0000269|PubMed:25466283}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.828
RVIS EVS: 0.46
RVIS percentile EVS: 78.59

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.596

Gene Damage Prediction

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