WDR25

Summary

WDR25 (WD repeat domain 25, HGNC:21064) is a protein-coding gene on chromosome 14q32.2, encoding WD repeat-containing protein 25 (Q64LD2). It is a selective cancer dependency (DepMap: 87.3% of cell lines).

This gene encodes a protein containing 7 WD repeats. WD repeats are approximately 30 to 40-amino acid domains containing several conserved residues, typically having a Tryptophan-Aspartic acid dipeptide (WD) at the C-terminal end. WD domains are involved in protein-protein interactions in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 79446 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 104 total
• Cancer dependency (DepMap): dependent in 87.3% of screened cell lines
• MANE Select transcript: NM_001161476

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21064
Approved symbol	WDR25
Name	WD repeat domain 25
Location	14q32.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC4645
Ensembl gene	ENSG00000176473
Ensembl biotype	protein_coding
OMIM	618059
Entrez	79446

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000335290, ENST00000402312, ENST00000542471, ENST00000554175, ENST00000554492, ENST00000554998, ENST00000555201, ENST00000555775, ENST00000555865, ENST00000557502, ENST00000557710, ENST00000878612, ENST00000878613, ENST00000878614, ENST00000937329, ENST00000962632, ENST00000962633

RefSeq mRNA: 6 — MANE Select: NM_001161476 NM_001161476, NM_001350947, NM_001350948, NM_001350949, NM_001387351, NM_024515

CCDS: CCDS32157

Canonical transcript exons

ENST00000402312 — 7 exons

Exon	Start	End
ENSE00001265131	100529820	100530303
ENSE00001334780	100380910	100381746
ENSE00002432665	100376485	100376495
ENSE00003489058	100529068	100529208
ENSE00003517705	100468021	100468168
ENSE00003664614	100525870	100526040
ENSE00003673336	100483994	100484124

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 86.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.1835 / max 186.7268, expressed in 1753 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141465	5.7244	1750
141466	0.2314	89
141470	0.0719	26
141468	0.0646	7
141469	0.0524	5
141464	0.0339	2
141467	0.0049	1

Top tissues by expression

277 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.25	gold quality
adenohypophysis	UBERON:0002196	82.64	gold quality
mucosa of transverse colon	UBERON:0004991	81.91	gold quality
gastrocnemius	UBERON:0001388	81.81	gold quality
popliteal artery	UBERON:0002250	81.68	gold quality
tibial artery	UBERON:0007610	81.65	gold quality
right adrenal gland cortex	UBERON:0035827	81.61	gold quality
right adrenal gland	UBERON:0001233	81.57	gold quality
left adrenal gland	UBERON:0001234	81.53	gold quality
islet of Langerhans	UBERON:0000006	81.43	gold quality
left adrenal gland cortex	UBERON:0035825	81.40	gold quality
muscle of leg	UBERON:0001383	81.28	gold quality
right lobe of thyroid gland	UBERON:0001119	80.84	gold quality
nucleus accumbens	UBERON:0001882	80.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.63	gold quality
left lobe of thyroid gland	UBERON:0001120	80.59	gold quality
cortical plate	UBERON:0005343	80.17	gold quality
aorta	UBERON:0000947	80.10	gold quality
pituitary gland	UBERON:0000007	80.05	gold quality
body of pancreas	UBERON:0001150	79.86	gold quality
anterior cingulate cortex	UBERON:0009835	79.86	gold quality
adrenal cortex	UBERON:0001235	79.75	gold quality
right frontal lobe	UBERON:0002810	79.75	gold quality
cingulate cortex	UBERON:0003027	79.73	gold quality
oocyte	CL:0000023	79.43	gold quality
thyroid gland	UBERON:0002046	79.34	gold quality
left coronary artery	UBERON:0001626	79.26	gold quality
apex of heart	UBERON:0002098	79.26	gold quality
stromal cell of endometrium	CL:0002255	79.17	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

11 targeting WDR25, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-7111-3P	97.80	66.75	1467
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-4286	97.20	64.37	1587

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 87.3% of screened cell lines.

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Wdr25	ENSMUSG00000040877
rattus_norvegicus	Wdr25	ENSRNOG00000004733

Paralogs (2): CDC40 (ENSG00000168438), WDR87 (ENSG00000171804)

Protein

Protein identifiers

WD repeat-containing protein 25 — Q64LD2 (reviewed: Q64LD2)

All UniProt accessions (5): Q64LD2, A0A384NPW5, G3V2K8, G3V367, H0YJW0

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed in heart, muscle, testis, ovary, uterus and prostate.

Isoforms (2)

UniProt ID	Names	Canonical?
Q64LD2-1	1	yes
Q64LD2-2	2

RefSeq proteins (6): NP_001154948, NP_001337876, NP_001337877, NP_001337878, NP_001374280, NP_078791 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR053053	WD_repeat_protein	Family

Pfam: PF00400

UniProt features (20 total): repeat 7, sequence variant 4, sequence conflict 3, splice variant 2, region of interest 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q64LD2-F1	68.82	0.43

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): MYOGENIN_Q6, MODULE_255, GCANCTGNY_MYOD_Q6, MODULE_317, CAGCTG_AP4_Q5, chr14q32, MODULE_69, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MARTENS_TRETINOIN_RESPONSE_UP, MODULE_37, PRC2_SUZ12_UP.V1_UP, BRCA1_DN.V1_UP, DCA_UP.V1_UP, BMI1_DN.V1_DN, KRAS.600.LUNG.BREAST_UP.V1_UP

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

1379 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WDR25	BEGAIN	Q9BUH8	743
WDR25	SLC25A29	Q8N8R3	594
WDR25	FAM8A1	Q9UBU6	533
WDR25	ANKRD50	Q9ULJ7	524
WDR25	TPRA1	Q86W33	510
WDR25	PDHA2	P29803	499
WDR25	SLC5A9	Q2M3M2	493
WDR25	FBXL14	Q8N1E6	460
WDR25	COA8	Q96IL0	448
WDR25	GAMT	Q14353	445
WDR25	ATP23	Q9Y6H3	444
WDR25	CMTM1	Q8IZ96	433
WDR25	GHRHR	Q02643	421
WDR25	DLK1	P15803	417
WDR25	FAT4	Q6V0I7	416

IntAct

29 interactions, top by confidence:

A	B	Type	Score
TRIM23	WDR25	psi-mi:“MI:0915”(physical association)	0.560
KRT31	WDR25	psi-mi:“MI:0915”(physical association)	0.560
WDR25	KRT40	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	WDR25	psi-mi:“MI:0915”(physical association)	0.560
WDR25	PNMA1	psi-mi:“MI:0915”(physical association)	0.560
PNMA1	WDR25	psi-mi:“MI:0915”(physical association)	0.560
WDR25	KRT31	psi-mi:“MI:0915”(physical association)	0.560
WDR25	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
WDR25	CCT7	psi-mi:“MI:0915”(physical association)	0.560
IMPDH1	BCAT2	psi-mi:“MI:0914”(association)	0.530
PSME3	WDR25	psi-mi:“MI:0915”(physical association)	0.370
IMPDH1	LCMT2	psi-mi:“MI:0914”(association)	0.350
IGFALS	HSPA5	psi-mi:“MI:0914”(association)	0.350
WDR25	CCT2	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
IMPDH1	MGST3	psi-mi:“MI:0914”(association)	0.350
WDR25	LRP6	psi-mi:“MI:0914”(association)	0.350
CCT2	WDR91	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350

BioGRID (66): WDR25 (Two-hybrid), WDR25 (Two-hybrid), WDR25 (Two-hybrid), KRT40 (Two-hybrid), NOTCH2NL (Two-hybrid), WDR25 (Reconstituted Complex), WDR25 (Two-hybrid), WDR25 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), WDR25 (Affinity Capture-RNA), WDR25 (Synthetic Lethality), WDR25 (Two-hybrid), WDR25 (Two-hybrid), WDR25 (Two-hybrid), WDR25 (Two-hybrid)

ESM2 similar proteins: A0A1L8GLK3, A0A8I6ASZ5, A0A974CYQ5, A4PES0, A4QNA8, A6NGE4, D2HHP1, D2HWM5, D3Z3I0, E6ZIJ1, E9Q349, F1ND48, O57473, P0C7V8, P0DOY1, P43254, P47817, P93471, Q28I90, Q3TLR7, Q4KLI9, Q4V837, Q58WW2, Q5QJC2, Q5R9B8, Q5RHI5, Q5XII5, Q60525, Q64LD2, Q66JG1, Q66JT0, Q6DFE0, Q6KAU8, Q6NRH1, Q6P1W0, Q6PCD5, Q80ZK9, Q8CBW4, Q8CIK8, Q8N5D0

Diamond homologs: A0AUS0, A1CGS0, A1CQL6, A1D3I2, A2QHM1, A2QPW4, A3LNW3, A3LVM1, A5DXE2, A6ZYM0, A7EZJ5, A7RHG8, A7RWD2, A7TLU2, A8IZG4, A8PWQ8, A9VDW7, B0G0Z3, B0XAF3, B0XQ15, B3MC74, B3NQR5, B3RNR8, B4GDM7, B4HRQ6, B4JW81, B4KTK4, B4LJT7, B4MY77, B4P7Q3, B4QFZ8, B5X212, B5X9P2, B6K1G6, B7QKS1, B9WHJ2, D5GBI7, E9Q349, G0SA60, G4MQX3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

104 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1994 predictions. Top by Δscore:

Variant	Effect	Δscore
14:100468168:GG:G	donor_loss	1.0000
14:100468170:T:A	donor_loss	1.0000
14:100483990:GTA:G	acceptor_loss	1.0000
14:100483991:TAG:T	acceptor_loss	1.0000
14:100483992:A:AG	acceptor_gain	1.0000
14:100483992:A:G	acceptor_loss	1.0000
14:100483992:AG:A	acceptor_gain	1.0000
14:100483993:G:GG	acceptor_gain	1.0000
14:100483993:GG:G	acceptor_gain	1.0000
14:100483993:GGA:G	acceptor_gain	1.0000
14:100484121:CAAGG:C	donor_loss	1.0000
14:100484122:AAG:A	donor_loss	1.0000
14:100484123:AGG:A	donor_loss	1.0000
14:100484124:GGTA:G	donor_loss	1.0000
14:100484125:GT:G	donor_loss	1.0000
14:100484126:T:A	donor_loss	1.0000
14:100525866:GCAGG:G	acceptor_loss	1.0000
14:100525867:CAG:C	acceptor_loss	1.0000
14:100525868:AG:A	acceptor_gain	1.0000
14:100525868:AGGT:A	acceptor_gain	1.0000
14:100525868:AGGTG:A	acceptor_loss	1.0000
14:100525869:G:C	acceptor_loss	1.0000
14:100525869:GG:G	acceptor_gain	1.0000
14:100525869:GGT:G	acceptor_gain	1.0000
14:100525869:GGTG:G	acceptor_gain	1.0000
14:100526038:CACG:C	donor_loss	1.0000
14:100526039:ACGT:A	donor_loss	1.0000
14:100526040:CGTA:C	donor_loss	1.0000
14:100526041:G:GC	donor_loss	1.0000
14:100526041:G:GG	donor_gain	1.0000

AlphaMissense

3553 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:100525996:T:A	W410R	0.999
14:100525996:T:C	W410R	0.999
14:100525948:A:C	S394R	0.998
14:100525950:C:A	S394R	0.998
14:100525950:C:G	S394R	0.998
14:100525945:A:C	S393R	0.997
14:100525947:C:A	S393R	0.997
14:100525947:C:G	S393R	0.997
14:100525994:C:A	A409D	0.997
14:100525998:G:C	W410C	0.997
14:100525998:G:T	W410C	0.997
14:100529152:T:C	F453L	0.997
14:100529154:C:A	F453L	0.997
14:100529154:C:G	F453L	0.997
14:100381684:T:A	W254R	0.996
14:100381684:T:C	W254R	0.996
14:100529117:T:C	F441S	0.996
14:100529153:T:C	F453S	0.996
14:100468096:T:A	W300R	0.995
14:100468096:T:C	W300R	0.995
14:100468123:A:C	S309R	0.995
14:100468125:T:A	S309R	0.995
14:100468125:T:G	S309R	0.995
14:100525997:G:C	W410S	0.995
14:100526033:T:C	I422T	0.995
14:100526033:T:G	I422S	0.995
14:100529082:C:G	C429W	0.995
14:100529170:T:G	Y459D	0.995
14:100525988:T:A	I407N	0.994
14:100526035:T:C	F423L	0.994

dbSNP variants (sampled 300 via entrez): RS1000015139 (14:100465820 A>G), RS1000019229 (14:100396150 G>A), RS1000028268 (14:100385882 C>T), RS1000052219 (14:100463154 A>C,G), RS1000085985 (14:100458941 G>A), RS1000118578 (14:100517565 C>T), RS1000125912 (14:100440359 G>A), RS1000136302 (14:100503116 T>A), RS1000168707 (14:100459451 C>A,T), RS1000236068 (14:100392706 C>A), RS1000260122 (14:100528208 C>T), RS1000262143 (14:100440592 A>G), RS1000290281 (14:100410027 C>T), RS1000322270 (14:100409746 G>C), RS1000323517 (14:100391607 C>G,T)

Disease associations

OMIM: gene MIM:618059 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): long QT syndrome (MONDO:0002442)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002541_99	Menarche (age at onset)	9.000000e-15
GCST003993_23	Menarche (age at onset)	1.000000e-14
GCST010002_160	Refractive error	3.000000e-10
GCST011122_5	Walking pace	9.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	increases expression, decreases expression	2
Tunicamycin	increases expression	2
Valproic Acid	affects expression, increases methylation	2
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Doxorubicin	decreases expression	1
Gallic Acid	decreases expression	1
Methapyrilene	decreases methylation	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Thapsigargin	increases expression	1

Clinical trials (associated diseases)

66 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval
NCT02876380	Not specified	COMPLETED	Prospective Identification of Long QT Syndrome in Fetal Life
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03544918	Not specified	COMPLETED	Prevalence of Congenital Long QT Syndrome and Acquired QT Prolongation in a Hospital Cohort
NCT03642405	Not specified	UNKNOWN	Drug-induced Repolarization ECG Changes
NCT03678311	Not specified	COMPLETED	Long QT Syndrome and Sleep Apnea