WDR59

protein-coding

WD repeat domain 59, the group of GATOR2 subcomplex|WD repeat domain containing

Gene summary

Predicted to enable signaling adaptor activity. Involved in cellular response to amino acid starvation and positive regulation of TORC1 signaling. Acts upstream of or within protein localization to plasma membrane. Located in lysosomal membrane. Part of GATOR2 complex. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_030581.4

Inheritance

—

ClinVar variants

U:150B:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.54

Max pathogenic AF

—

Genomic locus

chr16:74,871,362-75,000,173

External References & Databases

Ensembl (ENSG00000103091)

Transcript & Mutation Effects

hg38 • Region Span ~128.8 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 WDR59 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 138

not providedTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030581.4. 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			5 clinvar	6 clinvar	3 clinvar	14
missense			136 clinvar	2 clinvar	4 clinvar	142
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	150	8	7	165

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 94 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_030581.4	RefSeq	NP_085058.3	26	MANE Select
ENST00000262144.11	Ensembl	ENSP00000262144.6	26	MANE Select
NM_001324171.2	RefSeq	NP_001311100.1	17	Standard
NM_001324172.2	RefSeq	NP_001311101.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mTOR signaling pathway - Homo sapiens (human)

Biological Process

positive regulation of TOR signaling
cellular response to amino acid starvation

Molecular Function

protein binding

Cellular Component

lysosomal membrane
GATOR2 complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262144
Coding exons: 26
Length: 126604
Individuals with no LoFs: 125656
Homozygous LoFs: 0
Heterozygous LoFs: 91
Defined: 125747
p: 0.000362

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.25	503	588	0.855	0.0000356	6374
Missense (PolyPhen)		118	161.26	0.73176		1715
Synonymous	-3.66	291	222	1.31	0.0000133	1863
Loss of Function	3.30	32	59.4	0.538	0.00000319	624

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.00030	0.00029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.00052	0.00049	rare
South Asian	0.00020	0.00020	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: As a component of the GATOR subcomplex GATOR2, functions within the amino acid-sensing branch of the TORC1 signaling pathway. Indirectly activates mTORC1 and the TORC1 signaling pathway through the inhibition of the GATOR1 subcomplex (PubMed:23723238). It is negatively regulated by the upstream amino acid sensors SESN2 and CASTOR1 (PubMed:25457612, PubMed:27487210). {ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:25457612, ECO:0000269|PubMed:27487210}.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.784
RVIS EVS: -1.26
RVIS percentile EVS: 5.34

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.806

Gene Damage Prediction

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