WASF3

Summary

WASF3 (WASP family member 3, HGNC:12734) is a protein-coding gene on chromosome 13q12.13, encoding Actin-binding protein WASF3 (Q9UPY6). Downstream effector molecules involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton.

This gene encodes a member of the Wiskott-Aldrich syndrome protein family. The gene product is a protein that forms a multiprotein complex that links receptor kinases and actin. Binding to actin occurs through a C-terminal verprolin homology domain in all family members. The multiprotein complex serves to tranduce signals that involve changes in cell shape, motility or function. A pseudogene of this gene have been defined on chromosome 6. Alternative splicing results in multiple transcript variants

Source: NCBI Gene 10810 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 86 total
• Druggable target: yes
• MANE Select transcript: NM_006646

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12734
Approved symbol	WASF3
Name	WASP family member 3
Location	13q12.13
Locus type	gene with protein product
Status	Approved
Aliases	WAVE3, SCAR3, KIAA0900
Ensembl gene	ENSG00000132970
Ensembl biotype	protein_coding
OMIM	605068
Entrez	10810

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 18 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000335327, ENST00000361042, ENST00000496788, ENST00000671038, ENST00000887335, ENST00000887336, ENST00000887337, ENST00000887338, ENST00000887339, ENST00000887340, ENST00000887341, ENST00000887342, ENST00000916503, ENST00000916504, ENST00000916505, ENST00000916506, ENST00000916507, ENST00000942982, ENST00000942983

RefSeq mRNA: 2 — MANE Select: NM_006646 NM_001291965, NM_006646

CCDS: CCDS76626, CCDS9318

Canonical transcript exons

ENST00000335327 — 10 exons

Exon	Start	End
ENSE00000679574	26676549	26676724
ENSE00000679588	26682607	26682974
ENSE00000906597	26681054	26681320
ENSE00001376656	26612961	26613058
ENSE00001857008	26685688	26688948
ENSE00001863358	26557683	26557819
ENSE00003484063	26642261	26642403
ENSE00003510681	26671872	26671989
ENSE00003511128	26667517	26667670
ENSE00003572388	26665028	26665162

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 97.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.5157 / max 429.4280, expressed in 1383 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134491	17.5976	1376
134492	0.5423	229
134501	0.3141	163
134494	0.0245	3
134495	0.0151	3
134498	0.0099	3
134496	0.0065	3
134497	0.0056	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
substantia nigra pars compacta	UBERON:0001965	97.74	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.53	gold quality
paraflocculus	UBERON:0005351	97.33	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.21	gold quality
orbitofrontal cortex	UBERON:0004167	97.19	gold quality
cerebellar vermis	UBERON:0004720	97.07	gold quality
postcentral gyrus	UBERON:0002581	97.02	gold quality
lateral globus pallidus	UBERON:0002476	97.00	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.99	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.79	gold quality
secondary oocyte	CL:0000655	96.58	gold quality
parietal lobe	UBERON:0001872	96.44	gold quality
CA1 field of hippocampus	UBERON:0003881	96.42	gold quality
superior vestibular nucleus	UBERON:0007227	96.13	gold quality
superior frontal gyrus	UBERON:0002661	96.02	gold quality
medulla oblongata	UBERON:0001896	95.73	gold quality
pons	UBERON:0000988	95.47	gold quality
frontal pole	UBERON:0002795	95.25	gold quality
temporal lobe	UBERON:0001871	95.18	gold quality
amygdala	UBERON:0001876	95.18	gold quality
inferior olivary complex	UBERON:0002127	95.11	gold quality
entorhinal cortex	UBERON:0002728	95.11	gold quality
subthalamic nucleus	UBERON:0001906	95.07	gold quality
nucleus accumbens	UBERON:0001882	94.87	gold quality
prefrontal cortex	UBERON:0000451	94.79	gold quality
substantia nigra	UBERON:0002038	94.74	gold quality
caudate nucleus	UBERON:0001873	94.73	gold quality
cranial nerve II	UBERON:0000941	94.70	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.70	gold quality
midbrain	UBERON:0001891	94.61	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.32
E-GEOD-111727	no	225.07

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A, STAT3

miRNA regulators (miRDB)

137 targeting WASF3, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-515-5P	99.92	69.82	2343

Literature-anchored findings (GeneRIF, showing 40)

• patient with ganglioneuroblastoma carries an apparently balanced t(1:13)(q21:q12) reciprocal translocation. Positional cloning of the translocation breakpoint on chromosome 13 resulted in the mapping of the breakpoint between coding exon 2 and 3 of WAVE3 (PMID:12185600)
• the 3 WAVE isoforms exhibit common and distinct features and may potentially be involved in the regulation of actin cytoskeleton in platelets (PMID:15280206)
• during megakaryocytic differentiation, platelets expressed WAVE-1 and WAVE-2, whereas WAVE-3 expression was hardly to be detected. WAVE-3 expression was not changed by the differentiation (PMID:15670045)
• all three Scar/WAVE isoforms behave similarly and are likely to participate in the same kinds of protein complexes that regulate actin assembly (PMID:15752430)
• WAVE3-mediated migration in MDA-MB-231 cells via lamellipodia formation is activated downstream of PI3K and induced by PDGF (PMID:15826941)
• The WAVE3 is a member of the WASP/WAVE family of proteins, which play a critical role in the regulation of actin polymerization, cytoskeleton organization, and cell motility. (PMID:15907837)
• the activation of WAVE3 to promote actin remodeling is enhanced by the c-Abl-mediated tyrosine phosphorylation of WAVE3. (PMID:17623672)
• WAVE3 is pivotal in controlling the invasiveness of prostate cancer cells. (PMID:19395286)
• Studies identified a novel mechanism for the regulation of WAVE3 expression in cancer cells, which controls the invasive properties and morphology of cancer cells associated with their metastatic potential. (PMID:19801681)
• The study also identifies a critical role for WAVE3, downstream of miR-31, in the invasion-metastasis cascade. (PMID:21105030)
• coordinated expression patterns of the WASF3 metastasis promoter gene and the KISS1 metastasis suppressor gene appear to exert their influence through inhibition of NF-kappaB signaling, which in turn regulates MMP-9 production facilitating invasion. (PMID:21544801)
• HSP90 and HSP70 proteins are essential for stabilization and activation of WASF3 metastasis-promoting protein. (PMID:22315230)
• demonstrate WASF3 is a HIF1A-regulated gene and suggests a mechanism to explain the observation of elevated expression of WASF3 in advanced stage tumors (PMID:22581642)
• MMP-9 and WAVE3 were over-expressed in colorectal cancer tissues compared with normal mucosa. (PMID:22806308)
• WAVE3-depleted breast cancer cells move more slowly but more persistently on a 2-dimensional matrix. They typically only show one lamellipod. WAVE3 appears to have no role in driving invasiveness. Lamellipodial persistence is not crucial in 3-dimensions. (PMID:22909346)
• increased expression levels of WAVE3 are associated with the progression and metastasis of triple negative breast cancer (PMID:22952619)
• ZEB1/2 upregulation by WASF3 results from downregulation of KISS1, leading to the release of inhibition of nuclear factor (NF)kappaB by IkappaBalpha (PMID:23318438)
• these results define a novel signaling network whereby JAK2/STAT3 signaling creates a feed-forward loop to raise activated WASF3 levels that promote cancer cell motility. (PMID:23677069)
• Upregulated WAVE3 expression is essential for TGF-beta-mediated EMT and metastasis of triple-negative breast cancer cells. (PMID:24197660)
• We show that WAVE3-mediated modulation of NFkappaB is required for invadopodia formation as well as MMP9 expression and activity that are needed for cancer cells to degrade the ECM (PMID:25329315)
• WAVE3 promotes epithelial-mesenchymal transition of gastric cancer through upregulation of Snail. (PMID:25378074)
• WAVE3 is pivotal in controlling oncogenic phenotypes of human hepatocellular carcinoma cells. (PMID:25661390)
• stabilization of WASF3 function occurs through its interaction with ATAD3A and GRP78, which may provide a bridge between the ER and mitochondria, allowing communication between the two organelles (PMID:25823022)
• we show that WASF3 is present in the HER2 immunocomplex and suppression of WASF3 function leads to suppression of invasion even in the presence of HER2 expression.The engagement of WASF3 with the HER2/HER3 complex facilitates its phospho-activation and transcriptional upregulation, which is facilitated by HER2/HER3 activation of JAK/STAT signaling. (PMID:26804171)
• It was concluded that WAVE3 may represent a new adverse prognostic factor for patients with ICC. (PMID:26971088)
• Results implicate a contributory role of WAVE1 and -3 to the metastatic phenotype of PC-3 cells through their interaction with the ARP2/3 complex. (PMID:26977009)
• we show that stapled peptides targeting the interface between NCKAP1 and CYFIP1 destabilize the WASF3 complex… thereby suppressing invasion and metastasis of breast cancer cells. (PMID:27432794)
• studies provide a deeper understanding of the critical role for WASF3 in facilitating increased invasion potential in cancer cells expressing mutant RAS and supports the idea that targeting WASF3 in metastatic cells overexpressing RAS may be used to suppress invasion and metastasis (PMID:28233357)
• Results suggest that Wiskott-Aldrich syndrome verprolin-homologous protein 3 (WAVE3) may be pivotal in ovarian cancer cell motility, invasion and oncogenesis. (PMID:28476025)
• p63alpha protein up-regulates heat shock protein 70 expression via E2F1 transcription factor 1, promoting Wasf3/Wave3/MMP9 signaling and bladder cancer invasion (PMID:28794159)
• Study demonstrated that the expression levels of WAVE3 in pancreatic cancer tissues were prominently higher than those in the non-cancerous tissues which seems to be associated with lymphatic metastasis, poorly differentiated tumors. Furthermore, findings suggest that WAVE3 influences cell proliferation, migration and invasion via the AKT pathway. (PMID:29845225)
• Our analysis demonstrates that WASF3 expression correlates with poor outcomes and is a potential prognostic factor in gastric cancer patients. (PMID:31038356)
• Elevated WASF3 Expression Promotes Metastasis in Breast Cancer. (PMID:31542393)
• Asiatic Acid Interferes with Invasion and Proliferation of Breast Cancer Cells by Inhibiting WAVE3 Activation through PI3K/AKT Signaling Pathway. (PMID:32104680)
• These findings suggest that miR-93 functions as a metastasis suppressor and WASF3 was identified as a functional target of miR-93 (PMID:32307765)
• WASF3 silencing promotes proliferation, migration and invasiveness of gastric cancer cells; its knockdown depended on the inhibition of Atg12-mediated autophagy (PMID:32359534)
• WAVE3 upregulation in esophageal squamous cell carcinoma and its effect on the migration of human esophageal cancer cell lines in vitro. (PMID:32377706)
• Targeting WASF3 Signaling in Metastatic Cancer. (PMID:33467681)
• Phosphorylation of the proline-rich domain of WAVE3 drives its oncogenic activity in breast cancer. (PMID:33594155)
• SHOX2 cooperates with STAT3 to promote breast cancer metastasis through the transcriptional activation of WASF3. (PMID:34465361)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	wasf3a	ENSDARG00000059466
danio_rerio	wasf3b	ENSDARG00000062948
mus_musculus	Wasf3	ENSMUSG00000029636
rattus_norvegicus	Wasf3	ENSRNOG00000048898
drosophila_melanogaster	SCAR	FBGN0041781
caenorhabditis_elegans	wve-1	WBGENE00006958

Paralogs (2): WASF1 (ENSG00000112290), WASF2 (ENSG00000158195)

Protein

Protein identifiers

Actin-binding protein WASF3 — Q9UPY6 (reviewed: Q9UPY6)

Alternative names: Protein WAVE-3, Verprolin homology domain-containing protein 3, Wiskott-Aldrich syndrome protein family member 3

All UniProt accessions (3): A0A590UJ74, Q5T8P4, Q9UPY6

UniProt curated annotations — full annotation on UniProt →

Function. Downstream effector molecules involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape.

Subunit / interactions. Binds actin and the Arp2/3 complex.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Expressed in ovary and brain.

Post-translational modifications. Phosphorylation by ABL1 promotes lamellipodia formation and cell migration.

Domain organisation. Binds the Arp2/3 complex through the C-terminal region and actin through verprolin homology (VPH) domain.

Similarity. Belongs to the SCAR/WAVE family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UPY6-1	1	yes
Q9UPY6-2	2

RefSeq proteins (2): NP_001278894, NP_006637* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003124	WH2_dom	Domain
IPR028288	SCAR/WAVE_fam	Family

Pfam: PF02205

UniProt features (19 total): compositionally biased region 6, modified residue 4, region of interest 2, coiled-coil region 2, chain 1, domain 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UPY6-F1	66.48	0.28

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 (4): 151, 248, 337, 486

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-5663213	RHO GTPases Activate WASPs and WAVEs
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9664422	FCGR3A-mediated phagocytosis

MSigDB gene sets: 202 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_REGULATION_OF_ACTIN_NUCLEATION, LI_WILMS_TUMOR, GOBP_GLIAL_CELL_DEVELOPMENT, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_MYELINATION, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, MODULE_66, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_ENSHEATHMENT_OF_NEURONS, GOBP_POSITIVE_REGULATION_OF_ACTIN_NUCLEATION

GO Biological Process (10): cytoskeleton organization (GO:0007010), regulation of cell shape (GO:0008360), oligodendrocyte development (GO:0014003), lamellipodium assembly (GO:0030032), actin cytoskeleton organization (GO:0030036), actin filament polymerization (GO:0030041), positive regulation of myelination (GO:0031643), protein-containing complex assembly (GO:0065003), modification of postsynaptic actin cytoskeleton (GO:0098885), positive regulation of Arp2/3 complex-mediated actin nucleation (GO:2000601)

GO Molecular Function (4): actin binding (GO:0003779), protein kinase A regulatory subunit binding (GO:0034237), Arp2/3 complex binding (GO:0071933), protein binding (GO:0005515)

GO Cellular Component (8): cytoskeleton (GO:0005856), lamellipodium (GO:0030027), SCAR complex (GO:0031209), extracellular exosome (GO:0070062), glial cell projection (GO:0097386), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Fcgamma receptor (FCGR) dependent phagocytosis	1
Signaling by VEGF	1
RHO GTPase Effectors	1
RHO GTPase cycle	1
Leishmania phagocytosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
plasma membrane bounded cell projection	2
synapse	2
cellular anatomical structure	2
organelle organization	1
regulation of cell morphogenesis	1
regulation of biological quality	1
glial cell development	1
oligodendrocyte differentiation	1
lamellipodium organization	1
plasma membrane bounded cell projection assembly	1
cytoskeleton organization	1
actin filament-based process	1
actin polymerization or depolymerization	1
protein polymerization	1
regulation of myelination	1
positive regulation of nervous system process	1
myelination	1
positive regulation of cellular process	1
cellular component assembly	1
protein-containing complex organization	1
modification of postsynaptic structure	1
Arp2/3 complex-mediated actin nucleation	1
regulation of Arp2/3 complex-mediated actin nucleation	1
positive regulation of actin nucleation	1
cytoskeletal protein binding	1
protein kinase A binding	1
protein-containing complex binding	1
binding	1
intracellular membraneless organelle	1
cell leading edge	1
cytoplasm	1
protein-containing complex	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

946 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WASF3	NCKAP1	Q9Y2A7	968
WASF3	ABI2	Q9NYB9	960
WASF3	ABI1	Q8IZP0	942
WASF3	CYFIP1	Q7L576	888
WASF3	BRK1	Q8WUW1	882
WASF3	NCKAP1L	P55160	880
WASF3	WAS	P42768	866
WASF3	CYFIP2	Q96F07	832
WASF3	ABI3	Q9P2A4	804
WASF3	CDC42	P21181	777
WASF3	HSPA5	P11021	776
WASF3	BAIAP2	Q9UQB8	580
WASF3	AKT1	P31749	557
WASF3	WHAMM	Q8TF30	516
WASF3	ATAD3A	Q9NVI7	492

IntAct

52 interactions, top by confidence:

A	B	Type	Score
BRK1	HSBP1	psi-mi:“MI:0914”(association)	0.740
EGFR	WASF3	psi-mi:“MI:0915”(physical association)	0.650
EGFR	WASF3	psi-mi:“MI:2364”(proximity)	0.650
WASF3	EGFR	psi-mi:“MI:0915”(physical association)	0.650
NCK2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.640
WASF3	SMAD4	psi-mi:“MI:0915”(physical association)	0.550
SMAD4	WASF3	psi-mi:“MI:2364”(proximity)	0.550
SMAD4	WASF3	psi-mi:“MI:0915”(physical association)	0.550
WASHC3	WASH3P	psi-mi:“MI:0914”(association)	0.530
WASF3	HOXB9	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
AMZ1	SUSD5	psi-mi:“MI:0914”(association)	0.530
NHSL3	NCK2	psi-mi:“MI:0914”(association)	0.530
NCKAP1	NHSL1	psi-mi:“MI:0914”(association)	0.530
WASF3	CYFIP1	psi-mi:“MI:0914”(association)	0.530
WASF3	CAMK2D	psi-mi:“MI:0915”(physical association)	0.370
	ZNF316	psi-mi:“MI:0914”(association)	0.350
Cyfip2	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
TIMM50	ZNF724	psi-mi:“MI:0914”(association)	0.350
ABI2	OBSL1	psi-mi:“MI:0914”(association)	0.350
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ENG	IGKV2-28	psi-mi:“MI:0914”(association)	0.350

BioGRID (71): WASF3 (Two-hybrid), WASF3 (Affinity Capture-MS), WASF3 (Co-fractionation), WASF3 (Co-fractionation), WASF3 (PCA), WASF3 (Affinity Capture-MS), WASF3 (Affinity Capture-MS), WASF3 (Affinity Capture-MS), ABI1 (Affinity Capture-MS), NCKAP1 (Affinity Capture-MS), GTF2IRD1 (Affinity Capture-MS), BRK1 (Affinity Capture-MS), CMTR1 (Affinity Capture-MS), CYFIP2 (Affinity Capture-MS), HOXB9 (Affinity Capture-MS)

ESM2 similar proteins: A0JNI5, A2AJT4, A2AQ19, A4IFB1, B1H1X4, D3ZTQ1, O43290, P35269, Q05519, Q12872, Q13435, Q3THK3, Q3UJB0, Q3UQU0, Q3USH5, Q4V7C9, Q53F19, Q568R1, Q5EA53, Q5HZB6, Q5PQQ2, Q5R539, Q5RAD5, Q5XIW8, Q5ZM19, Q66I22, Q6AY96, Q6DDA4, Q6GLZ8, Q6INH5, Q6ZPZ3, Q8BZR9, Q8CFC7, Q8K194, Q8N2M8, Q8N5F7, Q8TF01, Q8VHI6, Q8WVK2, Q923D5

Diamond homologs: A2VDK6, Q0IIJ3, Q5BJU7, Q5NVG8, Q5XPJ9, Q8BH43, Q8R5H6, Q8VHI6, Q92558, Q9UPY6, Q9Y6W5, Q9LP46, Q54NF8

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ABL1	“up-regulates activity”	WASF3	phosphorylation
WASF3	“up-regulates activity”	Metastasis

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 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
RHO GTPases Activate WASPs and WAVEs	9	79.3×	4e-13
Parasite infection	5	48.1×	2e-06
Leishmania phagocytosis	5	48.1×	2e-06
FCGR3A-mediated phagocytosis	9	46.8×	2e-11
Regulation of actin dynamics for phagocytic cup formation	9	46.0×	2e-11
Signaling by VEGF	7	42.7×	1e-08
VEGFA-VEGFR2 Pathway	10	38.7×	1e-11
Fcgamma receptor (FCGR) dependent phagocytosis	5	38.7×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
Rac protein signal transduction	6	71.7×	6e-08
positive regulation of lamellipodium assembly	5	64.0×	3e-06
lamellipodium assembly	5	47.2×	1e-05
epidermal growth factor receptor signaling pathway	5	26.4×	1e-04
neuron migration	5	14.2×	2e-03
cell migration	7	9.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2087 predictions. Top by Δscore:

Variant	Effect	Δscore
13:26612960:GTTTT:G	acceptor_gain	1.0000
13:26642391:C:G	donor_gain	1.0000
13:26642402:GA:G	donor_gain	1.0000
13:26642404:G:GG	donor_gain	1.0000
13:26665023:TACA:T	acceptor_loss	1.0000
13:26665024:A:AG	acceptor_gain	1.0000
13:26665025:CAGGC:C	acceptor_loss	1.0000
13:26665026:A:AG	acceptor_gain	1.0000
13:26665026:A:T	acceptor_loss	1.0000
13:26665027:G:A	acceptor_loss	1.0000
13:26665027:G:GA	acceptor_gain	1.0000
13:26665027:GGC:G	acceptor_gain	1.0000
13:26665159:GAGG:G	donor_gain	1.0000
13:26665161:GG:G	donor_gain	1.0000
13:26665162:GG:G	donor_gain	1.0000
13:26665163:G:GG	donor_gain	1.0000
13:26665164:T:G	donor_loss	1.0000
13:26667515:A:AG	acceptor_gain	1.0000
13:26667516:G:GG	acceptor_gain	1.0000
13:26667516:GT:G	acceptor_gain	1.0000
13:26671847:T:A	acceptor_gain	1.0000
13:26671855:A:AG	acceptor_gain	1.0000
13:26671856:A:G	acceptor_gain	1.0000
13:26671858:ACATT:A	acceptor_gain	1.0000
13:26671860:A:AG	acceptor_gain	1.0000
13:26671860:ATT:A	acceptor_gain	1.0000
13:26671861:T:G	acceptor_gain	1.0000
13:26671871:GA:G	acceptor_gain	1.0000
13:26671969:A:T	donor_gain	1.0000
13:26671985:AAAAG:A	donor_loss	1.0000

AlphaMissense

3286 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:26642392:T:C	L41P	1.000
13:26642401:T:C	L44P	1.000
13:26665036:G:C	A48P	1.000
13:26665037:C:A	A48D	1.000
13:26665069:G:C	A59P	1.000
13:26665100:T:C	L69P	1.000
13:26665121:T:A	L76H	1.000
13:26665121:T:C	L76P	1.000
13:26665123:G:C	A77P	1.000
13:26665133:T:A	V80D	1.000
13:26665142:T:A	L83Q	1.000
13:26665142:T:C	L83P	1.000
13:26667523:T:A	L92Q	1.000
13:26667523:T:C	L92P	1.000
13:26667549:T:C	F101L	1.000
13:26667551:C:A	F101L	1.000
13:26667551:C:G	F101L	1.000
13:26671872:A:C	R141S	1.000
13:26671872:A:T	R141S	1.000
13:26671918:T:C	F157L	1.000
13:26671920:C:A	F157L	1.000
13:26671920:C:G	F157L	1.000
13:26671928:T:C	L160P	1.000
13:26671930:T:A	W161R	1.000
13:26671930:T:C	W161R	1.000
13:26671931:G:C	W161S	1.000
13:26671932:G:C	W161C	1.000
13:26671932:G:T	W161C	1.000
13:26671946:T:C	L166P	1.000
13:26676621:T:A	W205R	1.000

dbSNP variants (sampled 300 via entrez): RS1000024335 (13:26572546 G>A), RS1000034396 (13:26650823 A>C), RS1000039124 (13:26561035 G>C), RS1000064673 (13:26616531 A>T), RS1000071280 (13:26574041 T>C), RS1000076199 (13:26616849 C>T), RS1000112625 (13:26652426 T>G), RS1000123605 (13:26605397 G>A), RS1000135668 (13:26572834 G>A), RS1000181515 (13:26687516 T>C), RS1000182668 (13:26681220 C>T), RS1000188393 (13:26639787 C>A,G,T), RS1000222242 (13:26606547 G>A), RS1000238569 (13:26537946 T>A,C,G), RS1000298276 (13:26604568 G>A)

Disease associations

OMIM: gene MIM:605068 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002940_4	Sporadic pituitary adenoma	2.000000e-08
GCST006628_3	Systolic blood pressure	2.000000e-09
GCST009391_257	Metabolite levels	5.000000e-06
GCST009847_12	Hallux valgus	5.000000e-06
GCST90002401_53	Platelet distribution width	2.000000e-09
GCST90013421_35	Left-handedness	1.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0010426	triacylglycerol 54:8 measurement
EFO:0007984	platelet component distribution width
EFO:0009902	handedness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169205 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment, decreases expression	5
trichostatin A	affects cotreatment, decreases expression, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	3
mercuric bromide	decreases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Dexamethasone	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
sotorasib	affects cotreatment, decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5128525	Binding	Degradation of WASF3 in human serum starved MDA-MB-231 cells assessed as reduction in ABI2 expression at 2 uM measured after 72 hrs by Western blot analysis	In Silico Optimized Stapled Peptides Targeting WASF3 in Breast Cancer. — ACS Med Chem Lett

Cellosaurus cell lines

4 cell lines: 2 transformed cell line, 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3LA	Abcam HEK293T WASF3 KO 1	Transformed cell line	Female
CVCL_B3LB	Abcam HEK293T WASF3 KO 2	Transformed cell line	Female
CVCL_TX81	HAP1 WASF3 (-) 1	Cancer cell line	Male
CVCL_TX82	HAP1 WASF3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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