NWD1

protein-coding

NACHT and WD repeat domain containing 1, the group of WD repeat domain containing

Gene summary

The protein encoded by this gene is thought to be a cytosolic protein and predicted to contain a NACHT domain and multiple WD40 repeats. Increased expression of this gene was observed in some prostate cancer cell lines. Knocking down expression of this gene results in decreased androgen receptor protein levels, indicating that this gene may be important in modulating androgen receptor activity. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

MANE transcript

NM_001007525.5

Inheritance

—

ClinVar variants

U:252B:31

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr19:16,719,847-16,817,963

External References & Databases

Ensembl (ENSG00000188039)

Transcript & Mutation Effects

hg38 • Region Span ~98.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NWD1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 258

not providedTotal: 13

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001007525.5. 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			2 clinvar	4 clinvar	1 clinvar	7
missense			245 clinvar	20 clinvar	5 clinvar	270
nonsense			2 clinvar			2
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	252	25	6	283

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001007525.5	RefSeq	NP_001007526.3	17	MANE Select
ENST00000524140.7	Ensembl	ENSP00000428579.2	17	MANE Select
NM_001290355.3	RefSeq	NP_001277284.1	16	Standard
NM_001347994.1	RefSeq	NP_001334923.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

ATP binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000524140
Coding exons: 17
Length: 97988
Individuals with no LoFs: 125338
Homozygous LoFs: 3
Heterozygous LoFs: 406
Defined: 125747
p: 0.00163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.162	844	857	0.984	0.0000535	9187
Missense (PolyPhen)		183	193.8	0.94429		2255
Synonymous	0.383	372	382	0.975	0.0000250	3034
Loss of Function	1.65	48	62.0	0.774	0.00000322	647

Population LoF Frequency

Population	CAF	p-value	Status
African	0.012	0.011	notable
Latino/Admixed American	0.0016	0.0015	notable
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.0016	0.0016	notable
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00077	0.00074	rare
South Asian	0.0018	0.0018	notable
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in the control of androgen receptor (AR) protein steady-state levels. {ECO:0000269|PubMed:24681825}.;

Intolerance Scores

LoFtool: 0.937
RVIS EVS: 1.76
RVIS percentile EVS: 96.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.0950

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High