WASF2

Summary

WASF2 (WASP family member 2, HGNC:12733) is a protein-coding gene on chromosome 1p36.11, encoding Actin-binding protein WASF2 (Q9Y6W5). Downstream effector molecule 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. The published map location (PMID:10381382) has been changed based on recent genomic sequence comparisons, which indicate that the expressed gene is located on chromosome 1, and a pseudogene may be located on chromosome X. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10163 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 66 total
• Druggable target: yes
• MANE Select transcript: NM_006990

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12733
Approved symbol	WASF2
Name	WASP family member 2
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	WAVE2, SCAR2
Ensembl gene	ENSG00000158195
Ensembl biotype	protein_coding
OMIM	605875
Entrez	10163

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000536657, ENST00000618852, ENST00000874253, ENST00000874254, ENST00000874255, ENST00000874256, ENST00000937041, ENST00000937042, ENST00000937043, ENST00000937044, ENST00000937045, ENST00000966003, ENST00000966004

RefSeq mRNA: 2 — MANE Select: NM_006990 NM_001201404, NM_006990

CCDS: CCDS304, CCDS55582

Canonical transcript exons

ENST00000618852 — 9 exons

Exon	Start	End
ENSE00001037609	27412572	27412727
ENSE00001037614	27415985	27416102
ENSE00001037615	27418954	27419088
ENSE00001037624	27414833	27414963
ENSE00001037625	27418269	27418422
ENSE00001462180	27428761	27428933
ENSE00003718638	27489986	27490167
ENSE00003741573	27409692	27410206
ENSE00003744722	27404230	27408346

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 98.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.5734 / max 475.9939, expressed in 1825 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11235	47.0546	1825
11233	1.5816	892
11234	1.4432	868
11236	0.4940	249

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nipple	UBERON:0002030	98.47	gold quality
upper arm skin	UBERON:0004263	97.63	gold quality
tendon of biceps brachii	UBERON:0008188	97.63	gold quality
saphenous vein	UBERON:0007318	97.09	gold quality
pylorus	UBERON:0001166	97.00	gold quality
lower lobe of lung	UBERON:0008949	96.95	gold quality
cardia of stomach	UBERON:0001162	96.88	gold quality
pharyngeal mucosa	UBERON:0000355	96.87	gold quality
lower esophagus mucosa	UBERON:0035834	96.86	gold quality
trachea	UBERON:0003126	96.76	gold quality
mammary duct	UBERON:0001765	96.75	gold quality
parotid gland	UBERON:0001831	96.71	gold quality
inferior vagus X ganglion	UBERON:0005363	96.55	gold quality
buccal mucosa cell	CL:0002336	96.31	gold quality
synovial joint	UBERON:0002217	96.19	gold quality
ileal mucosa	UBERON:0000331	96.18	gold quality
penis	UBERON:0000989	96.13	gold quality
monocyte	CL:0000576	96.06	gold quality
leukocyte	CL:0000738	95.97	gold quality
esophagus mucosa	UBERON:0002469	95.97	gold quality
popliteal artery	UBERON:0002250	95.93	gold quality
tibial artery	UBERON:0007610	95.93	gold quality
mononuclear cell	CL:0000842	95.91	gold quality
blood	UBERON:0000178	95.91	gold quality
colonic epithelium	UBERON:0000397	95.91	gold quality
upper leg skin	UBERON:0004262	95.89	gold quality
superior surface of tongue	UBERON:0007371	95.74	gold quality
urethra	UBERON:0000057	95.69	gold quality
mucosa of stomach	UBERON:0001199	95.65	gold quality
esophagus	UBERON:0001043	95.61	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-76312	yes	1880.78
E-GEOD-93593	yes	7.75
E-CURD-122	yes	5.30
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXF2

miRNA regulators (miRDB)

152 targeting WASF2, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-3151-5P	99.86	63.83	1069

Literature-anchored findings (GeneRIF, showing 40)

• The WAVE2-Abi1-Nap1-PIR121 complex is as active as the WAVE2-Abi1 sub-complex in stimulating Arp2/3, and after Rac activation it is re-localized to the leading edge of ruffles in vivo. (PMID:15048123)
• reconstitution of the Wave-2 complex and a study of the molecular architecture (PMID:15070726)
• Results suggest that phosphatidylinositol (3,4,5)-triphosphate recruits WAVE2 to the polarized membrane and that this recruitment is essential for lamellipodium formation at the leading edge. (PMID:15107862)
• the 3 WAVE isoforms exhibit common and distinct features and may potentially be involved in the regulation of actin cytoskeleton in platelets (PMID:15280206)
• Abi-1-mediated coupling of Abl to WAVE2 promotes Abl-evoked WAVE2 tyrosine phosphorylation required to link WAVE2 with activated Rac and with actin polymerization and remodeling at the cell periphery. (PMID:15657136)
• WAVE-2 and WAVE-3 expression was not changed by the megakaryocytic differentiation; WAVE-1 and WAVE-2 moved from a detergent-soluble cytosolic fraction to insoluble cytoskeleton fraction after platelet aggregation (PMID:15670045)
• WAVE2 is a key component of the actin regulatory machinery in T cells and that it also participates in linking intracellular calcium store depletion to calcium release-activated calcium (CRAC) channel activation. (PMID:16401421)
• Coexpression of Arp2 and WAVE2 is correlated with poorer patient outcome. (PMID:16638851)
• Therefore, IRSp53 optimizes the activity of the WAVE2 complex in the presence of activated Rac and PIP(3). (PMID:16702231)
• c-Abl activates WAVE2 via tyrosine phosphorylation to promote actin remodeling in vivo; Abi-1 forms the crucial link between these two factors (PMID:16899465)
• WAVE2 expression is elevated in HCC tissues, which correlates with a poor prognosis, suggesting WAVE2 as a candidate prognostic marker of HCC. (PMID:17020969)
• Colocalization of Arp2 and WAVE2 is an independent risk factor for liver metastasis of colorectal carcinoma. (PMID:17459058)
• Data show that Chlamydia trachomatis activates Rac and promotes its interaction with WAVE2 and Abi-1 to activate the Arp2/3 complex resulting in the induction of actin cytoskeletal rearrangements that are required for invasion. (PMID:17501982)
• Results decribe a mechanism in which signals from the T cell receptor produce WAVE2-ARP2/3-mediated de novo actin polymerization, leading to integrin clustering and high-affinity binding through the recruitment of vinculin and talin. (PMID:17591693)
• Over-expression of WAVE2 is seen in node-positive cases as well as in moderately and poorly differentiated breast cancers. (PMID:18509249)
• Data suggest that the promotion of lamellipodia formation by HGF in MDA-MB-231 cells is Rac1-dependent and requires KIF5B-mediated transport of WAVE2 and IQGAP1 to the cell periphery along microtubules. (PMID:18514191)
• results suggest that long protrusions formed in a WAVE2- and microtubule-dependent manner may identify the cells at the later stage of invasion, possibly after the formation of invadopodia in the 3-D cultures (PMID:18795939)
• Results identify a mechanism by which the WAVE2 complex regulates T cell receptor signaling to Rap1 and integrin activation via Abl- and CrkL-C3G. (PMID:18809728)
• Phosphorylation of all five sites on endogenous WAVE2 and their mutation to non-phosphorylatable alanine residues leads to inhibition of WAVE2 function in vivo, was demonstrated. (PMID:19012317)
• Pak1 protein binds to WASF2 protein and is transported with WASF2 protein to the leading edge by stimulation with hepatocyte growth factor. (PMID:19162178)
• betaPIX and GIT1 regulate the hepatocyte growth factor-induced and Rac1-dependent membrane transport of WAVE2 and consequently, lamellipodia formation. (PMID:19303398)
• HSPC300 is associated with metastatic potential of lung squamous cell carcinoma through its interaction with WAVE2 (PMID:19576655)
• Data show that activation of the WAVE2 complex requires simultaneous interactions with prenylated Rac-GTP and acidic phospholipids, as well as a specific state of phosphorylation. (PMID:19917258)
• WAVE2-membrane targeting is directionally controlled by binding of the EB1-stathmin complex to WAVE2-bearing microtubules and by the interaction between WAVE2 and PIP3 produced near IGF-IR that is locally activated by IGF-I. (PMID:19925864)
• WAVE2 complexs with insulin receptor substrate p53 and is crucial for membrane targeting followed by local accumulation of WAVE2 at the leading edge of cells. (PMID:20621182)
• WAVE2 works as an A-kinase-anchoring protein that recruits PKA at membrane protrusions and plays a role in the enlargement of membrane protrusions induced by PKA activation (PMID:21119216)
• MYH9 is required for lamellipodia formation since it provides contractile forces and tension for the F-actin network to form convex arcs at the leading edge through constitutive binding to WAVE2 and colocalization with PIP(3) in response to IGF-I. (PMID:21184743)
• WAVE2 and WASp define parallel pathways to F-actin reorganization and function in NK cells; although WAVE2 was not required for NK cell innate function, it was accessible through adaptive immunity via IL-2. (PMID:21383498)
• Data suggest that ERK coordinates adhesion disassembly with WAVE2 regulatory complex activation and actin polymerization to promote productive leading edge advancement during cell migration. (PMID:21419341)
• results indicate that by mediating intensive F-actin accumulation at the sites of cell infiltration, WAVE2, N-WASP, and Mena are crucial for PI3K-dependent cell invasion induced by PDGF (PMID:21769917)
• We demonstrate that WAVE2-Arp2/3 is a major nucleator of actin assembly at the zonula adherens and likely acts in response to junctional Rac signaling (PMID:23051739)
• results suggest that SKAP2 negatively regulates cell migration and tumor invasion in fibroblasts and glioblastoma cells by suppressing actin assembly induced by the WAVE2-cortactin complex (PMID:23161539)
• Identification of an onco-suppressive role of miR-146a in gastric cancer cells by its reduction of WASF2 expression. (PMID:23435376)
• data reveal a critical role for WAVE2 complex in regulation of cellular signaling and epithelial morphogenesis (PMID:23691243)
• Decreased expression of Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2 may be involved in the development of pre-eclampsia. (PMID:24125947)
• these results suggest that Arp2/3 and the upstream regulator, WAVE2, are essential co-factors hijacked by HIV for intracellular migration, and may serve as novel targets to prevent HIV transmission. (PMID:24415754)
• Cortactin has a role as a scaffold for Arp2/3 and WAVE2 at the epithelial zonula adherens (PMID:24469447)
• WAVE2 is down-regulated in gastric cancer (PMID:24778020)
• WASp and WAVE2 differ in their dynamics and their associated proteins (PMID:25342748)
• the MCP1-induced cortactin phosphorylation is dependent on PLCb3-mediated PKC activation, and siRNA-mediated down-regulation of either of these molecules prevents cortactin interaction with WAVE2 (PMID:26490115)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	wasf2	ENSDARG00000024209
mus_musculus	Wasf2	ENSMUSG00000028868
rattus_norvegicus	Wasf2	ENSRNOG00000009805
drosophila_melanogaster	SCAR	FBGN0041781
caenorhabditis_elegans	wve-1	WBGENE00006958

Paralogs (2): WASF1 (ENSG00000112290), WASF3 (ENSG00000132970)

Protein

Protein identifiers

Actin-binding protein WASF2 — Q9Y6W5 (reviewed: Q9Y6W5)

Alternative names: Protein WAVE-2, Verprolin homology domain-containing protein 2, Wiskott-Aldrich syndrome protein family member 2

All UniProt accessions (1): Q9Y6W5

UniProt curated annotations — full annotation on UniProt →

Function. Downstream effector molecule involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Promotes formation of actin filaments. Part of the WAVE complex that regulates lamellipodia formation. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex.

Subunit / interactions. Binds actin and the Arp2/3 complex. Interacts with BAIAP2. Component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1, NCKAP1/NAP1 (NCKAP1l/HEM1 in hematopoietic cells) and WASF2/WAVE2. Directly interacts with BRK1. Interacts with FNBP1L (via the SH3 domain). (Microbial infection) Interacts with human cytomegalovirus protein UL135.

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Lamellipodium. Basolateral cell membrane.

Tissue specificity. Expressed in all tissues with strongest expression in placenta, lung, and peripheral blood leukocytes, but not in skeletal muscle.

Domain organisation. Binds and activates the Arp2/3 complex via the C-terminal domain. Interacts with actin via the WH2 domain.

Similarity. Belongs to the SCAR/WAVE family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y6W5-1	1	yes
Q9Y6W5-2	2

RefSeq proteins (2): NP_001188333, NP_008921* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003124	WH2_dom	Domain
IPR028288	SCAR/WAVE_fam	Family

Pfam: PF02205

UniProt features (17 total): mutagenesis site 7, region of interest 2, compositionally biased region 2, splice variant 2, chain 1, domain 1, helix 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2A40	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6W5-F1	68.74	0.30

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 (1): 474

Mutagenesis-validated functional residues (7):

Position	Phenotype
50	decreased interaction with wave complex; when associated with d-54.
51	decreased interaction with wave complex; when associated with d-40.
54	decreased interaction with wave complex; when associated with d-50.
124	constitutive induction of the formation of actin filaments. strongly enhances formation of lamellipodia.
150	constitutive induction of the formation of actin filaments. strongly enhances formation of lamellipodia.
160–161	constitutive induction of the formation of actin filaments. strongly enhances formation of lamellipodia.
40	decreased interaction with wave complex; when associated with d-51.

Function

Pathways and Gene Ontology

Reactome pathways

7 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-9013404	RAC2 GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9664422	FCGR3A-mediated phagocytosis

MSigDB gene sets: 350 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, AP1_01, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_REGULATION_OF_ACTIN_NUCLEATION, TTTGTAG_MIR520D, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_RUFFLE, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, GOBP_REGULATION_OF_LAMELLIPODIUM_ASSEMBLY, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION

GO Biological Process (17): angiogenesis (GO:0001525), ameboidal-type cell migration (GO:0001667), neuron migration (GO:0001764), endocytosis (GO:0006897), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), positive regulation of lamellipodium assembly (GO:0010592), Rac protein signal transduction (GO:0016601), lamellipodium assembly (GO:0030032), actin cytoskeleton organization (GO:0030036), actin filament-based movement (GO:0030048), megakaryocyte development (GO:0035855), negative regulation of stress fiber assembly (GO:0051497), lamellipodium morphogenesis (GO:0072673), postsynaptic actin cytoskeleton organization (GO:0098974), positive regulation of Arp2/3 complex-mediated actin nucleation (GO:2000601), cell motility (GO:0048870), postsynapse organization (GO:0099173)

GO Molecular Function (7): actin binding (GO:0003779), SH3 domain binding (GO:0017124), protein kinase A regulatory subunit binding (GO:0034237), cadherin binding (GO:0045296), protein kinase A binding (GO:0051018), Arp2/3 complex binding (GO:0071933), protein binding (GO:0005515)

GO Cellular Component (16): ruffle (GO:0001726), early endosome (GO:0005769), cytosol (GO:0005829), cell-cell junction (GO:0005911), actin cytoskeleton (GO:0015629), basolateral plasma membrane (GO:0016323), lamellipodium (GO:0030027), SCAR complex (GO:0031209), protein-containing complex (GO:0032991), synapse (GO:0045202), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RHO GTPase cycle	3
Fcgamma receptor (FCGR) dependent phagocytosis	1
Signaling by VEGF	1
RHO GTPase Effectors	1
Leishmania phagocytosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cell migration	2
lamellipodium organization	2
actin filament-based process	2
cell leading edge	2
plasma membrane bounded cell projection	2
cytoplasm	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
generation of neurons	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
adenylate cyclase activity	1
G protein-coupled receptor signaling pathway	1
regulation of lamellipodium assembly	1
lamellipodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
positive regulation of lamellipodium organization	1
small GTPase-mediated signal transduction	1
plasma membrane bounded cell projection assembly	1
cytoskeleton organization	1
megakaryocyte differentiation	1
myeloid cell development	1
negative regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
plasma membrane bounded cell projection morphogenesis	1
actin cytoskeleton organization	1
postsynaptic cytoskeleton organization	1
Arp2/3 complex-mediated actin nucleation	1
regulation of Arp2/3 complex-mediated actin nucleation	1
positive regulation of actin nucleation	1
cellular process	1
cellular component organization	1
synapse organization	1
cytoskeletal protein binding	1
protein domain specific binding	1
protein kinase A binding	1

Protein interactions and networks

STRING

1458 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WASF2	ABI1	Q8IZP0	998
WASF2	BAIAP2	Q9UQB8	997
WASF2	ABI2	Q9NYB9	996
WASF2	BRK1	Q8WUW1	996
WASF2	NCKAP1L	P55160	993
WASF2	NCKAP1	Q9Y2A7	990
WASF2	CYFIP2	Q96F07	990
WASF2	CYFIP1	Q7L576	981
WASF2	HCLS1	P14317	930
WASF2	CTTN	Q14247	928
WASF2	WAS	P42768	917
WASF2	CDC42	P21181	890
WASF2	ACTR2	P61160	888
WASF2	WASF1	Q92558	841
WASF2	EPS8	Q12929	776

IntAct

119 interactions, top by confidence:

A	B	Type	Score
WASF2	ABI1	psi-mi:“MI:0403”(colocalization)	0.830
ABI1	WASF2	psi-mi:“MI:0915”(physical association)	0.830
WASF2	ABI1	psi-mi:“MI:0915”(physical association)	0.830
BAIAP2	YWHAZ	psi-mi:“MI:0914”(association)	0.800
BAIAP2	YWHAQ	psi-mi:“MI:0914”(association)	0.740
BRK1	HSBP1	psi-mi:“MI:0914”(association)	0.740
VASP	CEP43	psi-mi:“MI:0914”(association)	0.740
WASF2	NCKAP1	psi-mi:“MI:0915”(physical association)	0.740
NCKAP1	YWHAH	psi-mi:“MI:0914”(association)	0.730
NCK2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.640
SPG11	AP5Z1	psi-mi:“MI:0914”(association)	0.620
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
ABL1	WASF2	psi-mi:“MI:0407”(direct interaction)	0.590
WASF2	BAIAP2	psi-mi:“MI:0915”(physical association)	0.590
BAIAP2	WASF2	psi-mi:“MI:0915”(physical association)	0.590
WASF2	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
ABI3	WASF2	psi-mi:“MI:0915”(physical association)	0.560
CYFIP2	WASF2	psi-mi:“MI:0915”(physical association)	0.560
BAIAP2	WASL	psi-mi:“MI:0914”(association)	0.550
WASF2	CYFIP1	psi-mi:“MI:0914”(association)	0.530

BioGRID (201): WASF2 (Two-hybrid), WASF2 (Affinity Capture-Western), ABI3 (Affinity Capture-Western), WASF2 (Reconstituted Complex), WASF2 (Reconstituted Complex), WASF2 (Reconstituted Complex), WASF2 (Affinity Capture-MS), WASF2 (Affinity Capture-MS), WASF2 (Affinity Capture-MS), WASF2 (Affinity Capture-MS), WASF2 (Co-fractionation), WASF2 (Co-fractionation), WASF2 (Co-fractionation), WASF2 (Co-fractionation), WASF2 (Co-fractionation)

ESM2 similar proteins: A1A5Q0, A2VDK6, A7Z063, B2RYF7, B5DF93, E1BTG2, O00401, O08816, P49140, P50551, Q02225, Q0IIJ3, Q13191, Q13435, Q28DN4, Q3TC46, Q3UHZ5, Q3UJB0, Q3UQU0, Q5BJU7, Q5NVG8, Q5PQQ2, Q5R8Q4, Q5T8P6, Q5U3K5, Q5ZKA6, Q62415, Q68EF0, Q6NZN0, Q6P0D5, Q6P5Q4, Q6PFT9, Q7Z5R6, Q86TB9, Q8BH43, Q8CH02, Q8IWZ8, Q8N8S7, Q8R5A3, Q8R5H6

Diamond homologs: A2VDK6, Q0IIJ3, Q5BJU7, Q5NVG8, Q5XPJ9, Q8BH43, Q8R5H6, Q8VHI6, Q92558, Q9UPY6, Q9Y6W5, Q5QNA6, Q5XPJ6, Q5XPK0, Q6AWX6, Q84TX2, Q9LP46, Q54NF8

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
CSNK2A1	down-regulates	WASF2	phosphorylation
WASF2	“form complex”	“WAVE complex”	binding
ABL1	“up-regulates activity”	WASF2	phosphorylation
BAIAP2	“up-regulates activity”	WASF2	binding
DTNBP1	“up-regulates activity”	WASF2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 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	14	47.8×	4e-18
Parasite infection	11	40.9×	1e-13
Leishmania phagocytosis	11	40.9×	1e-13
Activation of BAD and translocation to mitochondria	5	40.9×	2e-06
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	36.1×	4e-06
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	36.1×	4e-06
Fcgamma receptor (FCGR) dependent phagocytosis	11	33.0×	1e-12
FCGR3A-mediated phagocytosis	15	30.2×	2e-16

GO biological processes:

GO term	Partners	Fold	FDR
cell projection assembly	5	41.4×	4e-05
actin polymerization or depolymerization	6	40.7×	3e-06
positive regulation of actin filament polymerization	10	29.2×	1e-09
positive regulation of lamellipodium assembly	5	26.6×	2e-04
Rac protein signal transduction	5	24.9×	3e-04
lamellipodium assembly	5	19.6×	7e-04
ephrin receptor signaling pathway	6	18.3×	2e-04
cell motility	5	17.8×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2032 predictions. Top by Δscore:

Variant	Effect	Δscore
1:27408205:T:TA	donor_gain	1.0000
1:27408250:A:C	donor_gain	1.0000
1:27414829:CTA:C	donor_loss	1.0000
1:27414830:TA:T	donor_loss	1.0000
1:27414831:A:AC	donor_gain	1.0000
1:27414831:AC:A	donor_gain	1.0000
1:27414832:C:CC	donor_gain	1.0000
1:27414832:CC:C	donor_gain	1.0000
1:27414832:CCCA:C	donor_loss	1.0000
1:27414960:CTTT:C	acceptor_gain	1.0000
1:27414961:TTT:T	acceptor_gain	1.0000
1:27414961:TTTC:T	acceptor_loss	1.0000
1:27414962:TT:T	acceptor_gain	1.0000
1:27414963:TC:T	acceptor_loss	1.0000
1:27414964:C:CC	acceptor_gain	1.0000
1:27414965:T:C	acceptor_loss	1.0000
1:27414966:A:C	acceptor_gain	1.0000
1:27414969:A:AC	acceptor_gain	1.0000
1:27414969:A:C	acceptor_gain	1.0000
1:27415980:CTCAC:C	donor_loss	1.0000
1:27415983:A:AC	donor_gain	1.0000
1:27415983:AC:A	donor_gain	1.0000
1:27415984:C:CC	donor_gain	1.0000
1:27415984:C:G	donor_loss	1.0000
1:27415984:CC:C	donor_gain	1.0000
1:27415994:T:A	donor_gain	1.0000
1:27415999:T:TA	donor_gain	1.0000
1:27416005:T:A	donor_gain	1.0000
1:27416012:AT:A	donor_gain	1.0000
1:27416013:T:TA	donor_gain	1.0000

AlphaMissense

3230 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:27408253:G:T	A478D	1.000
1:27408254:C:G	A478P	1.000
1:27408256:A:T	I477N	1.000
1:27408259:C:G	R476P	1.000
1:27408260:G:T	R476S	1.000
1:27408262:C:G	R475P	1.000
1:27408263:G:T	R475S	1.000
1:27408268:A:C	L473W	1.000
1:27408268:A:G	L473S	1.000
1:27408271:A:C	I472S	1.000
1:27408271:A:G	I472T	1.000
1:27408271:A:T	I472N	1.000
1:27408337:A:G	L450P	1.000
1:27408337:A:T	L450Q	1.000
1:27409700:A:C	I444S	1.000
1:27409700:A:G	I444T	1.000
1:27409700:A:T	I444N	1.000
1:27409704:C:G	A443P	1.000
1:27409709:A:G	L441P	1.000
1:27409709:A:T	L441H	1.000
1:27409712:A:G	L440P	1.000
1:27416028:A:G	L165P	1.000
1:27416042:C:A	W160C	1.000
1:27416042:C:G	W160C	1.000
1:27416043:C:G	W160S	1.000
1:27416044:A:G	W160R	1.000
1:27416044:A:T	W160R	1.000
1:27416046:A:G	L159P	1.000
1:27416054:G:C	F156L	1.000
1:27416054:G:T	F156L	1.000

dbSNP variants (sampled 300 via entrez): RS1000012443 (1:27437738 T>C), RS1000016163 (1:27478479 T>C,G), RS1000022915 (1:27463801 A>T), RS1000028274 (1:27421430 C>T), RS1000131181 (1:27474104 T>TC), RS1000199106 (1:27431274 T>C), RS1000244309 (1:27448635 G>A,C,T), RS1000263775 (1:27424185 G>A), RS1000298770 (1:27489824 G>C), RS1000340374 (1:27424560 T>A), RS1000428216 (1:27481175 G>A,C,T), RS1000437392 (1:27461154 AAAAC>A), RS1000588408 (1:27488474 G>T), RS1000611618 (1:27430947 GA>G,GAA), RS1000618602 (1:27455374 G>A)

Disease associations

OMIM: gene MIM:605875 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007267_111	Systolic blood pressure	4.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067159 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 2 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.07	Kd	8535	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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	2149774: Binding affinity to human WASF2 incubated for 45 mins by Kinobead based pull down assay	kd	8.5353	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression, affects cotreatment	3
Particulate Matter	increases abundance, increases expression, affects cotreatment	3
sodium arsenite	increases expression, affects binding, increases reaction	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	decreases expression	1
arsenite	increases methylation	1
cobaltous chloride	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
aflatoxin B2	increases methylation	1
isobutyl alcohol	increases expression, affects cotreatment, increases abundance	1
epigallocatechin gallate	affects cotreatment, increases 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, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	decreases expression	1
Temozolomide	affects response to substance	1
Vorinostat	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	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
CHEMBL5652816	Binding	Binding affinity to human WASF2 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

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2L8	Abcam HeLa WASF2 KO	Cancer cell line	Female
CVCL_TX80	HAP1 WASF2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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