WDR1

Summary

WDR1 (WD repeat domain 1, HGNC:12754) is a protein-coding gene on chromosome 4p16.1, encoding WD repeat-containing protein 1 (O75083). Induces disassembly of actin filaments in conjunction with ADF/cofilin family proteins. It is a selective cancer dependency (DepMap: 69.4% of cell lines).

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.

Source: NCBI Gene 9948 — RefSeq curated summary.

At a glance

• Gene–disease (curated): periodic fever, immunodeficiency, and thrombocytopenia syndrome (Strong, GenCC)
• GWAS associations: 13
• Clinical variants (ClinVar): 567 total — 9 pathogenic
• Phenotypes (HPO): 17
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 69.4% of screened cell lines
• MANE Select transcript: NM_017491

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12754
Approved symbol	WDR1
Name	WD repeat domain 1
Location	4p16.1
Locus type	gene with protein product
Status	Approved
Aliases	AIP1
Ensembl gene	ENSG00000071127
Ensembl biotype	protein_coding
OMIM	604734
Entrez	9948

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 16 protein_coding, 12 protein_coding_CDS_not_defined, 7 nonsense_mediated_decay, 5 retained_intron

ENST00000264785, ENST00000499869, ENST00000502702, ENST00000502962, ENST00000504739, ENST00000505543, ENST00000505851, ENST00000506246, ENST00000508079, ENST00000508949, ENST00000509600, ENST00000509695, ENST00000510848, ENST00000514319, ENST00000515018, ENST00000515743, ENST00000561486, ENST00000699786, ENST00000699787, ENST00000699788, ENST00000699789, ENST00000699790, ENST00000699791, ENST00000699792, ENST00000699793, ENST00000699794, ENST00000699795, ENST00000699796, ENST00000699797, ENST00000699798, ENST00000699799, ENST00000867001, ENST00000867002, ENST00000867003, ENST00000918694, ENST00000918695, ENST00000918696, ENST00000950909, ENST00000950910, ENST00000950911

RefSeq mRNA: 2 — MANE Select: NM_017491 NM_005112, NM_017491

CCDS: CCDS54739, CCDS54740

Canonical transcript exons

ENST00000499869 — 15 exons

Exon	Start	End
ENSE00001492128	10097711	10097891
ENSE00002063287	10116651	10116799
ENSE00003499472	10088664	10088741
ENSE00003503929	10087707	10087940
ENSE00003510949	10084443	10084530
ENSE00003543883	10083022	10083178
ENSE00003559213	10078891	10079001
ENSE00003582961	10077753	10077926
ENSE00003585322	10077304	10077448
ENSE00003616956	10081357	10081444
ENSE00003650773	10088293	10088373
ENSE00003651155	10098992	10099139
ENSE00003651186	10103896	10103986
ENSE00003977604	10116113	10116234
ENSE00003977638	10074339	10075484

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 185.8296 / max 1019.3506, expressed in 1828 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51361	79.4545	1825
51362	60.7213	1824
51364	30.7672	1819
51363	5.8893	1724
51356	2.8339	1289
51360	1.4523	795
51359	1.0993	504
51358	1.0886	583
51355	0.7097	431
51357	0.7020	388

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
popliteal artery	UBERON:0002250	99.29	gold quality
tibial artery	UBERON:0007610	99.28	gold quality
aorta	UBERON:0000947	99.17	gold quality
smooth muscle tissue	UBERON:0001135	99.13	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.13	gold quality
right coronary artery	UBERON:0001625	99.12	gold quality
lower esophagus	UBERON:0013473	99.12	gold quality
saphenous vein	UBERON:0007318	99.06	gold quality
body of uterus	UBERON:0009853	99.06	gold quality
stromal cell of endometrium	CL:0002255	99.05	gold quality
parotid gland	UBERON:0001831	99.04	gold quality
thoracic aorta	UBERON:0001515	99.02	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.02	gold quality
ascending aorta	UBERON:0001496	99.01	gold quality
cauda epididymis	UBERON:0004360	99.00	gold quality
left uterine tube	UBERON:0001303	98.99	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.99	gold quality
colonic mucosa	UBERON:0000317	98.98	gold quality
left coronary artery	UBERON:0001626	98.92	gold quality
descending thoracic aorta	UBERON:0002345	98.90	gold quality
coronary artery	UBERON:0001621	98.85	gold quality
sigmoid colon	UBERON:0001159	98.82	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.80	gold quality
myometrium	UBERON:0001296	98.76	gold quality
mucosa of stomach	UBERON:0001199	98.73	gold quality
monocyte	CL:0000576	98.68	gold quality
colon	UBERON:0001155	98.68	gold quality
transverse colon	UBERON:0001157	98.68	gold quality
leukocyte	CL:0000738	98.67	gold quality
large intestine	UBERON:0000059	98.67	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	34.49
E-CURD-122	yes	23.11
E-HCAD-11	yes	18.94
E-HCAD-10	yes	16.14
E-MTAB-7052	no	307.52
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

96 targeting WDR1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-1299	99.77	71.24	2389

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 69.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 25)

• AIP1/WDR1 could abort the severing/disassembly activity somewhat still carried out due to phosphorylated ADF/cofilin (PMID:15629458)
• Data indicates that Aip1 plays an important role in directional cell migration by restricting the stimulus-induced membrane protrusion to one direction via promoting cofilin activity. (PMID:18494608)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• Studies indicate that CUL4 uses a large beta-propeller protein, DDB1, as a linker to interact with a subset of WD40 proteins. (PMID:19818632)
• The QKI RNA-binding proteins regulate oligodendrocyte differentiation by modulating the expression of AIP-1. (PMID:20631256)
• Data suggest that anti-WD repeat domain 1 (WDR1) antibody could be applied for serological screening of papillary thyroid carcinoma (PTC) and undifferentiated thyroid carcinoma (UTC), and could be an efficient and inexpensive biomarker. (PMID:23215816)
• Studies suggest that vascular endothelial growth factor may be responsible for upregulated P-glycoprotein expression. (PMID:23293323)
• WD repeat-containing protein 1 was confirmed as being significantly overexpressed in interstitial fluid from ovarian carcinomas compared to healthy ovarian tissue. (PMID:23707566)
• When maternal environmental tobacco smoke was considered, fifteen of 135 single nucleotide polymorphism (SNPs) mapping to SLC2A9 and 9 of 59 SNPs in WDR1 gave P values approaching genome-wide significance. (PMID:24516586)
• Demonstrate a previously unanticipated role of Aip1 in regulating the structure and remodeling of intestinal epithelial junctions and early steps of epithelial morphogenesis. (PMID:25792565)
• Identify positive correlations between WDR1 and CLNK gene polymorphisms in Chinese-Tibetan gout populations. (PMID:26438387)
• A/A" genotype of rs12498927 was associated with increased risk of gout. (PMID:27173277)
• STAT3 bound to the 5’ upstream sequence (-1971 to -1964), a putative promoter region, of WDR1 gene, and its activation induced WDR1 overexpression in breast cancer cells. (PMID:27521604)
• Mutations in WDR1 affect neutrophil morphology, motility, and function, causing a novel primary immunodeficiency (PMID:27557945)
• These data suggest that WDR1 plays an important role in suppressing platelet activity, where it alters the actin cytoskeleton dynamics, and downregulation of WDR1 may contribute to the platelet-mediated pathogenesis of cardiovascular disease. (PMID:27609643)
• homozygous missense L153F/L293F mutation in the actin regulatory gene WDR1 causes a new autoinflammatory disease in humans, with periodic fevers, immunodeficiency, and intermittent thrombocytopenia (PFIT). (PMID:27994071)
• MRTF-A-miR-206-WDR1 form feedback loop to regulate breast cancer cell migration. (PMID:28822708)
• Functions of WDR1 in actin filament dynamics and cytoskeletal regulation in health and disease have been described. (Review) (PMID:29056508)
• WDR1 is an EYA3-specific substrate, which implies that EYA3 is a key modulator of the cytoskeletal reorganization (PMID:29440662)
• Deficiency of the actin regulator WDR1 in human subjects is associated with a paucity of B-cell progenitors in the bone marrow and lack of switched memory B cells in the periphery. WDR1 missense mutations lead to aberrant assembly of both T- and B-cell immunologic synapses. (PMID:29751004)
• Based on this finding and on the finding that actin remodeling is required for hepatic secretion, the authors further confirmed that WDR1 is a phosphoprotein that regulates secretion. (PMID:30158666)
• WD repeat-containing protein 1 maintains beta-Catenin activity to promote pancreatic cancer aggressiveness. (PMID:32601462)
• Catastrophic actin filament bursting by cofilin, Aip1, and coronin. (PMID:32723865)
• YAP signaling is involved in WDR1-regulated proliferation and migration of non-small-cell lung cancer cells. (PMID:35861209)
• WDR1 promotes prostate cancer progression through Wnt/beta-catenin signaling. (PMID:38743149)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	WDR1	ENSDARG00000114022
mus_musculus	Wdr1	ENSMUSG00000005103
rattus_norvegicus	Wdr1	ENSRNOG00000028498
drosophila_melanogaster	flr	FBGN0260049
caenorhabditis_elegans		WBGENE00006810
caenorhabditis_elegans		WBGENE00010685

Protein

Protein identifiers

WD repeat-containing protein 1 — O75083 (reviewed: O75083)

Alternative names: Actin-interacting protein 1, NORI-1

All UniProt accessions (11): O75083, A0A8V8TNT7, A0A8V8TNU2, A0A8V8TP22, A0A8V8TP31, A0A8V8TPA9, A0A8V8TQ69, A0A8V8TQ74, A0A8V8TQK0, D6RD66, V9HWG7

UniProt curated annotations — full annotation on UniProt →

Function. Induces disassembly of actin filaments in conjunction with ADF/cofilin family proteins. Enhances cofilin-mediated actin severing. Involved in cytokinesis. Involved in chemotactic cell migration by restricting lamellipodial membrane protrusions. Involved in myocardium sarcomere organization. Required for cardiomyocyte growth and maintenance. 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. Involved in assembly and maintenance of epithelial apical cell junctions and plays a role in the organization of the perijunctional actomyosin belt.

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Podosome. Cell junction.

Tissue specificity. Expressed in peripheral blood mononuclear cells (at protein level).

Disease relevance. Periodic fever, immunodeficiency, and thrombocytopenia syndrome (PFITS) [MIM:150550] An immunologic disorder with variable manifestations including early-onset recurrent respiratory infections, stomatitis, cutaneous infections, and neutropenia. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the WD repeat AIP1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75083-1	1	yes
O75083-3	2

RefSeq proteins (2): NP_005103, NP_059830* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR011045	N2O_reductase_N	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF00400

UniProt features (31 total): repeat 13, sequence variant 10, modified residue 6, chain 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9QFQ	ELECTRON MICROSCOPY	2.76
9QFW	ELECTRON MICROSCOPY	3.16

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75083-F1	96.57	0.96

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 28, 81, 95, 115, 238, 480

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation

MSigDB gene sets: 0 (showing top):

GO Biological Process (18): neutrophil mediated immunity (GO:0002446), sensory perception of sound (GO:0007605), regulation of cell shape (GO:0008360), actin filament depolymerization (GO:0030042), actin filament fragmentation (GO:0030043), platelet formation (GO:0030220), regulation of actin filament depolymerization (GO:0030834), positive regulation of actin filament depolymerization (GO:0030836), cortical cytoskeleton organization (GO:0030865), locomotion (GO:0040011), establishment of planar polarity of follicular epithelium (GO:0042247), apical junction assembly (GO:0043297), maintenance of epithelial cell apical/basal polarity (GO:0045199), sarcomere organization (GO:0045214), regulation of oligodendrocyte differentiation (GO:0048713), regulation of ventricular cardiac muscle cell membrane repolarization (GO:0060307), neutrophil migration (GO:1990266), actin cytoskeleton organization (GO:0030036)

GO Molecular Function (3): actin filament binding (GO:0051015), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (15): podosome (GO:0002102), extracellular region (GO:0005576), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), cell junction (GO:0030054), cortical actin cytoskeleton (GO:0030864), extracellular exosome (GO:0070062), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), actin cytoskeleton (GO:0015629), cell projection (GO:0042995), synapse (GO:0045202), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
actin filament depolymerization	3
cytoskeleton organization	2
cell junction	2
myeloid leukocyte mediated immunity	1
sensory perception of mechanical stimulus	1
regulation of cell morphogenesis	1
regulation of biological quality	1
actin polymerization or depolymerization	1
protein depolymerization	1
myeloid cell differentiation	1
platelet morphogenesis	1
anatomical structure formation involved in morphogenesis	1
regulation of actin polymerization or depolymerization	1
regulation of protein depolymerization	1
regulation of actin filament depolymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of protein depolymerization	1
positive regulation of supramolecular fiber organization	1
biological_process	1
establishment of planar polarity	1
establishment or maintenance of polarity of follicular epithelium	1
cell-cell junction assembly	1
maintenance of apical/basal cell polarity	1
establishment or maintenance of epithelial cell apical/basal polarity	1
myofibril assembly	1
actomyosin structure organization	1
regulation of glial cell differentiation	1
oligodendrocyte differentiation	1
regulation of cardiac muscle cell membrane repolarization	1
ventricular cardiac muscle cell membrane repolarization	1
granulocyte migration	1
actin filament-based process	1
actin binding	1
protein-containing complex binding	1
cytoskeletal protein binding	1
binding	1
actin-based cell projection	1
cytoplasm	1
membrane	1

Protein interactions and networks

STRING

1674 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WDR1	CFL2	Q9Y281	985
WDR1	CFL1	P23528	985
WDR1	FLNA	P21333	689
WDR1	GSN	P06396	673
WDR1	CAPZB	P47756	658
WDR1	SMCR8	Q8TEV9	651
WDR1	ACTN1	P12814	633
WDR1	ZNF518B	Q9C0D4	623
WDR1	CORO1A	P31146	612
WDR1	PFN4	Q8NHR9	579
WDR1	CORO2A	Q92828	567
WDR1	DSTN	P18282	547
WDR1	PFN1	P07737	543
WDR1	A0A0A6YYL4	A0A0A6YYL4	542
WDR1	TWF2	Q6IBS0	540

IntAct

89 interactions, top by confidence:

A	B	Type	Score
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
WDR1	ACTB	psi-mi:“MI:0915”(physical association)	0.560
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
FOS	MYO1C	psi-mi:“MI:2364”(proximity)	0.480
SRPK1	WDR1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
SYVN1	WDR1	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
HSPB2	WDR1	psi-mi:“MI:0915”(physical association)	0.370
WDR1	CSNK2B	psi-mi:“MI:0915”(physical association)	0.370
MYH9	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ANLN	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MYO18A	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MYO1C	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MYO19	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
FLNA	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Lima1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
LIMA1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Calml3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Tmod3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Tpm1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Coro1c	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
DBN1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
SYNPO	LMO7	psi-mi:“MI:0914”(association)	0.350
MAPRE1	CTNNB1	psi-mi:“MI:0914”(association)	0.350
Myo1c	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Myh9	GOSR1	psi-mi:“MI:0914”(association)	0.350
MYH9	NAP1L1	psi-mi:“MI:0914”(association)	0.350
CAPZA2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
IQGAP1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PPP1CB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (308): WDR1 (Affinity Capture-RNA), WDR1 (Affinity Capture-RNA), WDR1 (Affinity Capture-MS), WDR1 (Affinity Capture-MS), ATP6AP2 (Co-fractionation), CALR (Co-fractionation), CFL1 (Co-fractionation), CFL2 (Co-fractionation), DSTN (Co-fractionation), ENO1 (Co-fractionation), ENO2 (Co-fractionation), GOT1 (Co-fractionation), GPI (Co-fractionation), HSPE1 (Co-fractionation), IFI30 (Co-fractionation)

ESM2 similar proteins: A0A1W5T363, A5DGL8, A5DVY3, A5GFN6, A8QBF3, A8WVX8, B0XFT7, B3N4C7, B4GSH1, B4I195, B4JB43, B4Q354, G0SEA3, O02195, O14301, O42937, O75083, O88342, O93277, P27133, P40066, P41838, P78406, Q16K15, Q26613, Q29L19, Q2KJH4, Q38942, Q3SWS8, Q4R6D2, Q54DM1, Q5AI86, Q5E9A4, Q5FVA9, Q5RF99, Q5RKI0, Q6CI08, Q6DIF4, Q6PAX7, Q759L2

Diamond homologs: A1CJY4, A1D7I5, A2QEV8, A3LX18, A4RDD7, A5DGL8, A5DVY3, A6RUL1, A6ZMK5, A7EF03, A7RM20, A7TH19, A8QBF3, A8WVX8, B0BNA7, B0XFT7, B0XYC8, B3MVL6, B3N4C7, B4GSH1, B4I195, B4JB43, B4KGX9, B4LUA5, B4N0L0, B4NW98, B4Q354, B5FZ19, C5FWH1, D4AZ50, D4DG66, E3LB80, O02195, O14435, O35353, O43071, O60508, O75083, O88342, P0CS32

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Sensory processing of sound	6	27.2×	5e-05
FCGR3A-mediated phagocytosis	6	16.5×	2e-04
Regulation of actin dynamics for phagocytic cup formation	6	16.2×	2e-04
Signaling by ALK fusions and activated point mutants	7	15.5×	7e-05
Sensory processing of sound by inner hair cells of the cochlea	6	14.4×	3e-04
VEGFA-VEGFR2 Pathway	6	12.3×	6e-04
Deubiquitination	5	9.1×	4e-03
Sensory Perception	6	8.4×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
platelet aggregation	5	19.4×	3e-03
regulation of apoptotic process	7	6.7×	1e-02
negative regulation of apoptotic process	12	4.8×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	0
Uncertain significance	162
Likely benign	342
Benign	22

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
3246741	NC_000004.11:g.(?2357152)(15176083_?)del	Pathogenic
810680	NM_017491.5(WDR1):c.392T>G (p.Phe131Cys)	Pathogenic
974600	NM_017491.5(WDR1):c.16AAG[1] (p.Lys7del)	Pathogenic
974601	NM_017491.5(WDR1):c.1270G>A (p.Val424Met)	Pathogenic
974602	NM_017491.5(WDR1):c.361G>A (p.Gly121Arg)	Pathogenic
974603	NM_017491.5(WDR1):c.856C>G (p.Leu286Val)	Pathogenic
974604	NM_017491.5(WDR1):c.435C>G (p.His145Gln)	Pathogenic
974605	NM_017491.5(WDR1):c.1715A>T (p.Asp572Val)	Pathogenic
974606	NM_017491.5(WDR1):c.877C>T (p.Leu293Phe)	Pathogenic

SpliceAI

2941 predictions. Top by Δscore:

Variant	Effect	Δscore
4:10077077:G:C	donor_gain	1.0000
4:10077299:GTCA:G	donor_loss	1.0000
4:10077300:TCAC:T	donor_loss	1.0000
4:10077301:CA:C	donor_loss	1.0000
4:10077302:ACCTT:A	donor_loss	1.0000
4:10077303:C:A	donor_loss	1.0000
4:10077444:TTCTC:T	acceptor_gain	1.0000
4:10077446:CTC:C	acceptor_gain	1.0000
4:10077446:CTCCT:C	acceptor_loss	1.0000
4:10077447:TC:T	acceptor_gain	1.0000
4:10077448:CC:C	acceptor_gain	1.0000
4:10077448:CCTA:C	acceptor_loss	1.0000
4:10077449:C:CC	acceptor_gain	1.0000
4:10077450:T:G	acceptor_loss	1.0000
4:10077453:T:C	acceptor_gain	1.0000
4:10077453:T:TC	acceptor_gain	1.0000
4:10077456:CAGG:C	acceptor_gain	1.0000
4:10077457:A:T	acceptor_gain	1.0000
4:10077459:G:C	acceptor_gain	1.0000
4:10077459:G:GC	acceptor_gain	1.0000
4:10077460:T:C	acceptor_gain	1.0000
4:10077460:T:TC	acceptor_gain	1.0000
4:10077749:TCA:T	donor_loss	1.0000
4:10077750:CACC:C	donor_loss	1.0000
4:10077751:A:AC	donor_gain	1.0000
4:10077751:AC:A	donor_gain	1.0000
4:10077751:ACCG:A	donor_loss	1.0000
4:10077752:C:CA	donor_gain	1.0000
4:10077752:CC:C	donor_gain	1.0000
4:10077752:CCG:C	donor_gain	1.0000

AlphaMissense

4024 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:10075449:A:G	W584R	1.000
4:10075449:A:T	W584R	1.000
4:10077361:C:G	D553H	1.000
4:10077375:G:T	A548D	1.000
4:10083075:G:C	S381R	1.000
4:10083075:G:T	S381R	1.000
4:10083077:T:G	S381R	1.000
4:10087877:A:G	W261R	1.000
4:10087877:A:T	W261R	1.000
4:10087934:A:G	W242R	1.000
4:10087934:A:T	W242R	1.000
4:10088727:A:C	F191L	1.000
4:10088727:A:T	F191L	1.000
4:10088729:A:G	F191L	1.000
4:10099007:C:T	G121E	1.000
4:10099021:C:A	R116S	1.000
4:10099021:C:G	R116S	1.000
4:10099041:A:G	W110R	1.000
4:10099041:A:T	W110R	1.000
4:10099116:A:G	W85R	1.000
4:10099116:A:T	W85R	1.000
4:10075418:G:A	S594F	0.999
4:10075424:G:T	T592K	0.999
4:10075427:A:T	V591D	0.999
4:10077343:A:G	W559R	0.999
4:10077343:A:T	W559R	0.999
4:10077360:T:A	D553V	0.999
4:10077360:T:G	D553A	0.999
4:10077400:A:G	W540R	0.999
4:10077400:A:T	W540R	0.999

dbSNP variants (sampled 300 via entrez): RS1000009735 (4:10090041 G>T), RS1000119594 (4:10115770 G>A,C,T), RS1000165031 (4:10074603 G>A), RS1000223487 (4:10088362 A>G), RS1000281065 (4:10117518 C>G,T), RS1000352355 (4:10076396 A>C,T), RS1000514553 (4:10098663 C>T), RS1000645450 (4:10100575 C>G), RS1000686925 (4:10088216 GGAGT>G), RS1000689111 (4:10075302 T>C,G), RS1000903578 (4:10109356 C>A), RS1000913231 (4:10109194 C>T), RS1000938492 (4:10098866 C>G,T), RS1000965239 (4:10107063 C>T), RS1000977881 (4:10079387 C>T)

Disease associations

OMIM: gene MIM:604734 | disease phenotypes: MIM:150550, MIM:618009

GenCC curated gene-disease

Disease	Classification	Inheritance
periodic fever, immunodeficiency, and thrombocytopenia syndrome	Strong	Autosomal recessive

Mondo (2): periodic fever, immunodeficiency, and thrombocytopenia syndrome (MONDO:0007883), intellectual developmental disorder 61 (MONDO:0032485)

Orphanet (1): Periodic fever-immunodeficiency-thrombocytopenia syndrome (Orphanet:652522)

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001328	Specific learning disability
HP:0001744	Splenomegaly
HP:0001875	Decreased total neutrophil count
HP:0001954	Recurrent fever
HP:0002014	Diarrhea
HP:0002110	Bronchiectasis
HP:0002716	Lymphadenopathy
HP:0002719	Recurrent infections
HP:0004854	Intermittent thrombocytopenia
HP:0006532	Recurrent pneumonia
HP:0009098	Chronic oral candidiasis
HP:0010976	Decreased total B cell count
HP:0011107	Recurrent aphthous stomatitis
HP:0025452	Pyoderma gangrenosum
HP:0025615	Abscess
HP:0031394	Abnormal CD4:CD8 ratio

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000130_1	Urate levels	2.000000e-15
GCST001115_2	Schizophrenia (age at onset)	5.000000e-06
GCST001247_6	Cardiovascular disease risk factors	9.000000e-71
GCST001374_1	Uric acid levels	2.000000e-19
GCST002348_1	Cleft plate (environmental tobacco smoke interaction)	2.000000e-06
GCST006061_19	Atrial fibrillation	2.000000e-09
GCST006629_93	Pulse pressure	6.000000e-12
GCST008058_224	Estimated glomerular filtration rate	5.000000e-12
GCST008059_145	Estimated glomerular filtration rate	9.000000e-12
GCST008971_34	Urate levels	1.000000e-12
GCST010512_2	Serum uric acid levels	3.000000e-13
GCST010512_3	Serum uric acid levels	3.000000e-15
GCST012338_9	Gout	5.000000e-17

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004847	age at onset
EFO:0004761	uric acid measurement
EFO:0008361	environmental tobacco smoke exposure measurement
EFO:0005763	pulse pressure measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562721	Lazy Leukocyte Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066472 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.09	Kd	81.7	nM	CHEMBL5653589
7.09	ED50	81.7	nM	CHEMBL5653589
5.57	Kd	2688	nM	CHEMBL3752910
5.57	ED50	2688	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149775: Binding affinity to human WDR1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0817	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149775: Binding affinity to human WDR1 incubated for 45 mins by Kinobead based pull down assay	kd	2.6875	uM

CTD chemical–gene interactions

64 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, decreases methylation, increases expression	4
Formaldehyde	increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	affects expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
methylmercuric chloride	increases expression	1
alpha-pinene	affects cotreatment, increases expression, increases oxidation, increases abundance	1
pirinixic acid	affects binding, decreases expression, increases activity	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
quinoline	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
ON 01910	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
1-(2-chlorobenzyl)-5’-phenyl-3’H-spiro(indoline-3,2’-(1,3,4)thiadiazol)-2-one	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652817	Binding	Binding affinity to human WDR1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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