WASF1

Summary

WASF1 (WASP family member 1, HGNC:12732) is a protein-coding gene on chromosome 6q21, encoding Actin-binding protein WASF1 (Q92558). Downstream effector molecule involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton.

The protein encoded by this gene, a member of the Wiskott-Aldrich syndrome protein (WASP)-family, plays a critical role downstream of Rac, a Rho-family small GTPase, in regulating the actin cytoskeleton required for membrane ruffling. It has been shown to associate with an actin nucleation core Arp2/3 complex while enhancing actin polymerization in vitro. Wiskott-Aldrich syndrome is a disease of the immune system, likely due to defects in regulation of actin cytoskeleton. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 8936 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with absent language and variable seizures (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 142 total — 8 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 30
• MANE Select transcript: NM_003931

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12732
Approved symbol	WASF1
Name	WASP family member 1
Location	6q21
Locus type	gene with protein product
Status	Approved
Aliases	WAVE1, SCAR1, KIAA0269, WAVE, WAVE-1
Ensembl gene	ENSG00000112290
Ensembl biotype	protein_coding
OMIM	605035
Entrez	8936

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 35 protein_coding

ENST00000265601, ENST00000359451, ENST00000368938, ENST00000392586, ENST00000392587, ENST00000392588, ENST00000392589, ENST00000419252, ENST00000444391, ENST00000447287, ENST00000875406, ENST00000875407, ENST00000875408, ENST00000875409, ENST00000875410, ENST00000875411, ENST00000875412, ENST00000875413, ENST00000875414, ENST00000875415, ENST00000875416, ENST00000875417, ENST00000920453, ENST00000920454, ENST00000920455, ENST00000920456, ENST00000920457, ENST00000920458, ENST00000963040, ENST00000963041, ENST00000963042, ENST00000963043, ENST00000963044, ENST00000963045, ENST00000963046

RefSeq mRNA: 4 — MANE Select: NM_003931 NM_001024934, NM_001024935, NM_001024936, NM_003931

CCDS: CCDS5080

Canonical transcript exons

ENST00000392589 — 11 exons

Exon	Start	End
ENSE00001374313	110160635	110160732
ENSE00001448326	110178598	110178742
ENSE00001613254	110179439	110179670
ENSE00003888760	110099819	110100679
ENSE00003889881	110101588	110102216
ENSE00003889912	110107077	110107194
ENSE00003892661	110113326	110113460
ENSE00003892873	110127469	110127629
ENSE00003894832	110105407	110105579
ENSE00003895604	110108528	110108681
ENSE00003895648	110103378	110103557

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 99.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.3241 / max 703.3271, expressed in 1687 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75035	27.7721	1636
75039	1.5614	950
75040	1.3992	707
75038	0.6033	220
75036	0.5989	350
75029	0.1819	65
75037	0.1190	49
75028	0.0500	21
75033	0.0313	17
75034	0.0070	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.63	gold quality
CA1 field of hippocampus	UBERON:0003881	99.16	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.95	gold quality
orbitofrontal cortex	UBERON:0004167	98.78	gold quality
superior frontal gyrus	UBERON:0002661	98.60	gold quality
postcentral gyrus	UBERON:0002581	98.44	gold quality
parietal lobe	UBERON:0001872	98.40	gold quality
primary visual cortex	UBERON:0002436	98.16	gold quality
entorhinal cortex	UBERON:0002728	98.16	gold quality
occipital lobe	UBERON:0002021	97.93	gold quality
middle temporal gyrus	UBERON:0002771	97.93	gold quality
prefrontal cortex	UBERON:0000451	97.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.50	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.48	gold quality
secondary oocyte	CL:0000655	97.33	gold quality
Ammon’s horn	UBERON:0001954	97.27	gold quality
ganglionic eminence	UBERON:0004023	97.24	gold quality
cerebral cortex	UBERON:0000956	97.19	gold quality
endothelial cell	CL:0000115	97.16	gold quality
frontal cortex	UBERON:0001870	97.14	gold quality
frontal lobe	UBERON:0016525	97.14	gold quality
pons	UBERON:0000988	97.06	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.01	gold quality
neocortex	UBERON:0001950	96.87	gold quality
telencephalon	UBERON:0001893	96.60	gold quality
oocyte	CL:0000023	96.40	gold quality
adult organism	UBERON:0007023	96.36	gold quality
nucleus accumbens	UBERON:0001882	96.32	gold quality
embryo	UBERON:0000922	96.07	gold quality
temporal lobe	UBERON:0001871	95.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.25
E-CURD-122	yes	5.41

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF5, GATA3

miRNA regulators (miRDB)

99 targeting WASF1, 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-6798-5P	100.00	65.77	699
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1277-5P	100.00	73.95	5056
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-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881

Literature-anchored findings (GeneRIF, showing 40)

• Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck: we propose that Rac1 and Nck cause dissociation of the WAVE1 complex, which releases active WAVE1-HSPC300 and leads to actin nucleation. (PMID:12181570)
• Results suggest that recruitment of factors by Wiskott-Aldrich Syndrome protein (WASP) and Scar1 stimulates cellular actin-based motility and actin nucleation with the Arp2/3 complex. (PMID:12429845)
• WAVE1 may act as a scaffold to recruit the NADPH oxidase to a complex involved with both cytoskeletal regulation and downstream JNK activation (PMID:12855698)
• the 3 WAVE isoforms exhibit common and distinct features and may potentially be involved in the regulation of actin cytoskeleton in platelets (PMID:15280206)
• Dictyostelium discoideum has been used to remove genetically SCAR complex members to ascertain their specific roles. (PMID:15506982)
• WAVE-1 expression was associated with megakaryocytic differentiation; WAVE-1 and WAVE-2 moved from a detergent-soluble cytosolic fraction to insoluble cytoskeleton fraction after platelet aggregation (PMID:15670045)
• NESH (Abi-3), like Abi-1 and Abi-2, is a component of the Abi/WAVE complex, but likely plays a different role in the regulation of c-Abl. (PMID:17101133)
• the Hem-1/Nap1 component of the Scar/WAVE complex localizes to propagating waves that appear to organize the leading edge of a motile neutrophil (PMID:17696648)
• WAVE1 is critical for formation of oligodendrocyte lamellae and myelin sheaths–REVIEW (PMID:17901257)
• WAVE1 is involved in multi-drug resistance through regulation the level of mdrl and Bcl-2. (PMID:17939402)
• WAVE1 dephosphorylation and activation are likely associated with mitochondrial redistribution and dendritic spine morphogenesis. (PMID:18287015)
• Results suggest that WAVE and the Arp2/3 complex jointly orchestrate different types of actin-based plasma membrane protrusions by promoting ruffling and inhibiting mDia2-induced filopodia. (PMID:18516090)
• The WAVE1 expression increased in children with ALL. WAVE1 may be related to the development of ALL and may be severed as a marker for the evaluation of the severity of ALL in children. (PMID:18947485)
• Dimerization act in hierarchical fashion, enabling WASP/WAVE proteins to integrate different classes of inputs to produce a wide range of cellular actin responses in Wiskoo Aldrich syndrome. (PMID:18995840)
• WAVE1 and p22phox expression in PBMCs increased and was associated with the disease course in children with acute lymphocytic leukemia (ALL). (PMID:19222940)
• WAVE accumulation may be involved in Abeta/amyloid precursor protein mediated-tangle modification (PMID:19497998)
• CIP4 is a new ArgBP2 interacting protein that modulates the ArgBP2 mediated control of WAVE1 phosphorylation and cancer cell migration. (PMID:19631450)
• WAVE1 might be involved in the migration and invasion of K562 cells through regulation of the expression level of MMP-2. (PMID:19731823)
• WAVE1 regulates Bcl-2 localization and phosphorylation in leukemia cells. (PMID:19890377)
• Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex (PMID:20368433)
• Higher levels of WAVE1 in the bone marrow indicate an unfavorable prognosis in children with AML. (PMID:20426950)
• Arf GTPases may be central components in WAVE signalling, acting directly, alongside Rac1. (PMID:21844371)
• mDia1 and WAVE2 are important Src homology 3 domain partners of IRSp53 in forming filopodia. (PMID:22179776)
• Study finds that WAVE1 overexpression is associated with an unfavorable prognosis. WAVE1 is an independent prognostic factor for EOC, which suggests that it is a novel and crucial predictor for EOC metastasis. (PMID:22721732)
• Scar/WAVE regulatory complex and N-WASP play opposing roles in 3D epithelial cell migration (PMID:23273897)
• mRNAs encoding structural and regulatory components of the WAVE complex are localized to the leading edge of the cell, suggesting that localized protein synthesis plays a pivotal role in controlling cell spreading and migration. (PMID:23452202)
• WAVE1 might promote the proliferative and invasive malignant behaviors through the activation of the PI3K/AKT and p38MAPK signaling pathways in epithelial ovarian cancer. (PMID:23680521)
• D620N mutation in VPS35 restricts WASH complex recruitment to endosomes, and reveals a novel role for the WASH complex in autophagosome formation. (PMID:24819384)
• The WAVE complex is the main activator of the Arp2/3 complex for actin filament nucleation and assembly in the lamellipodia of moving cells. (PMID:25355952)
• WAVE1 has unique activities independent of Arp2/3 complex that can govern both the growth rates and architectures of actin filament networks. Elongation inhibitory effects of WAVE1 were mapped to its WH2 (“V”) domain. (PMID:25473116)
• a role for ARF6 in linking EGF-receptor signaling to Rac1 recruitment and activation at the plasma membrane to promote breast cancer cell directed migration (PMID:25799492)
• we propose that WASF1 status defines a subtype of androgen deprivation therapy -resistant prostate cancer patients (PMID:25906751)
• A decrease in amounts of WASF1 mRNA was also observed in human Alzheimer’s disease brains, suggesting clinical relevance of the negative feedback circuit involved in homeostatic regulation of Abeta production (PMID:26280122)
• Results from a study on gene expression variability markers in early-stage human embryos shows that WASF1 is a putative expression variability marker for the 3-day, 8-cell embryo stage. (PMID:26288249)
• 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)
• Results suggested that WAVE1 is a critical pro-autophagic protein capable of enhancing cell survival and regulating chemoresistance in leukemia cells potentially through the Beclin1/Bcl-2 and Beclin1/PI3K- complex-dependent pathways. (PMID:27035872)
• WASP and SCAR drive pseudopod formation and are conserved in actin-filled pseudopod-based motility. (PMID:28473602)
• De novo heterozygous mutations in WASF1 cause a rare form of intellectual disability. (PMID:29961568)
• YAP was associated with cell migration in oral squamous cell carcinoma, and this process was regulated by YAP/WAVE1. (PMID:30697796)
• WAVE complex is required for neutrophil polarity and motility. (PMID:31600188)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	wasf1	ENSDARG00000060349
mus_musculus	Wasf1	ENSMUSG00000019831
rattus_norvegicus	Wasf1	ENSRNOG00000047476
drosophila_melanogaster	SCAR	FBGN0041781
caenorhabditis_elegans	wve-1	WBGENE00006958

Paralogs (2): WASF3 (ENSG00000132970), WASF2 (ENSG00000158195)

Protein

Protein identifiers

Actin-binding protein WASF1 — Q92558 (reviewed: Q92558)

Alternative names: Protein WAVE-1, Verprolin homology domain-containing protein 1, Wiskott-Aldrich syndrome protein family member 1

All UniProt accessions (4): Q92558, Q5SZK3, Q5SZK4, Q5SZK5

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. As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes. Also involved in the regulation of mitochondrial dynamics.

Subunit / interactions. Component of the WAVE1 complex composed of ABI2, CYFIP1 or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a heterodimer containing NCKAP1 and CYFIP1 interacts with a heterotrimer formed by WAVE1, ABI2 and BRK1. CYFIP2 binds to activated RAC1 which causes the complex to dissociate, releasing activated WASF1. The complex can also be activated by NCK1. Binds actin and the Arp2/3 complex. Interacts with BAIAP2. Interacts with SHANK3; the interaction mediates the association of SHANK3 with the WAVE1 complex. Interacts with ABI1 (via N-terminus). Interacts with SORBS2; this interaction greatly enhances phosphorylation by ABL1 and dephosphorylation by PTPN12 and might mediate partial to focal adhesion sites.

Subcellular location. Cytoplasm. Cytoskeleton. Synapse. Cell junction. Focal adhesion.

Tissue specificity. Highly expressed in brain. Lowly expressed in testis, ovary, colon, kidney, pancreas, thymus, small intestine and peripheral blood.

Post-translational modifications. Phosphorylated on tyrosine residues by ABL1 and dephosphorylated by PTPN12.

Disease relevance. Neurodevelopmental disorder with absent language and variable seizures (NEDALVS) [MIM:618707] A disorder characterized by neurodevelopmental abnormalities, including moderate to profound intellectual disability, with autistic features, seizures, severe impairments in speech, and gross motor delay. The disease is caused by variants affecting the gene represented in this entry.

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.

RefSeq proteins (4): NP_001020105, NP_001020106, NP_001020107, NP_003922* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003124	WH2_dom	Domain
IPR028288	SCAR/WAVE_fam	Family

Pfam: PF02205

UniProt features (29 total): helix 9, compositionally biased region 8, modified residue 3, region of interest 3, sequence variant 2, turn 2, chain 1, domain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3P8C	X-RAY DIFFRACTION	2.29
4N78	X-RAY DIFFRACTION	2.43
7USC	ELECTRON MICROSCOPY	3
7USD	ELECTRON MICROSCOPY	3
7USE	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92558-F1	67.26	0.29

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 (3): 341, 341, 489

Function

Pathways and Gene Ontology

Reactome pathways

6 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-9013423	RAC3 GTPase cycle
R-HSA-9664422	FCGR3A-mediated phagocytosis

MSigDB gene sets: 394 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, LEE_NEURAL_CREST_STEM_CELL_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_REGULATION_OF_ACTIN_NUCLEATION, GOBP_GROWTH, AACYNNNNTTCCS_UNKNOWN, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, GOMF_GTPASE_BINDING, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, IWANAGA_E2F1_TARGETS_NOT_INDUCED_BY_SERUM

GO Biological Process (14): receptor-mediated endocytosis (GO:0006898), mitochondrion organization (GO:0007005), Rac protein signal transduction (GO:0016601), actin cytoskeleton organization (GO:0030036), actin filament polymerization (GO:0030041), positive regulation of neurotrophin TRK receptor signaling pathway (GO:0051388), protein-containing complex assembly (GO:0065003), lamellipodium morphogenesis (GO:0072673), dendrite extension (GO:0097484), modification of postsynaptic actin cytoskeleton (GO:0098885), dendritic transport of mitochondrion (GO:0098939), cellular response to brain-derived neurotrophic factor stimulus (GO:1990416), positive regulation of Arp2/3 complex-mediated actin nucleation (GO:2000601), neuron projection development (GO:0031175)

GO Molecular Function (6): actin binding (GO:0003779), protein kinase A regulatory subunit binding (GO:0034237), protein kinase A binding (GO:0051018), Arp2/3 complex binding (GO:0071933), protein binding (GO:0005515), small GTPase binding (GO:0031267)

GO Cellular Component (14): mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), cytoskeleton (GO:0005856), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), lamellipodium (GO:0030027), SCAR complex (GO:0031209), dendrite cytoplasm (GO:0032839), protein-containing complex (GO:0032991), postsynapse (GO:0098794), cytoplasm (GO:0005737), mitochondrion (GO:0005739), synapse (GO:0045202), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RHO GTPase cycle	2
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
cytoplasm	3
cellular anatomical structure	3
cell junction	2
endocytosis	1
organelle organization	1
small GTPase-mediated signal transduction	1
cytoskeleton organization	1
actin filament-based process	1
actin polymerization or depolymerization	1
protein polymerization	1
positive regulation of signal transduction	1
neurotrophin TRK receptor signaling pathway	1
regulation of neurotrophin TRK receptor signaling pathway	1
cellular component assembly	1
protein-containing complex organization	1
lamellipodium organization	1
plasma membrane bounded cell projection morphogenesis	1
neuron projection extension	1
modification of postsynaptic structure	1
dendrite cytoplasm	1
mitochondrion transport along microtubule	1
dendritic transport	1
cellular response to nerve growth factor stimulus	1
Arp2/3 complex-mediated actin nucleation	1
regulation of Arp2/3 complex-mediated actin nucleation	1
positive regulation of actin nucleation	1
neuron development	1
plasma membrane bounded cell projection organization	1
cytoskeletal protein binding	1
protein kinase A binding	1
protein binding	1
protein-containing complex binding	1
binding	1
GTPase binding	1
mitochondrial membrane	1
organelle outer membrane	1
intracellular membraneless organelle	1
cell-substrate junction	1
cytoskeleton	1
cell leading edge	1

Protein interactions and networks

STRING

1328 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WASF1	ABI2	Q9NYB9	998
WASF1	NCKAP1	Q9Y2A7	998
WASF1	BRK1	Q8WUW1	998
WASF1	CYFIP2	Q96F07	997
WASF1	CYFIP1	Q7L576	995
WASF1	ABI1	Q8IZP0	994
WASF1	NCKAP1L	P55160	979
WASF1	WAS	P42768	929
WASF1	SRGAP3	O43295	922
WASF1	CDC42	P21181	922
WASF1	PRKACA	P17612	909
WASF1	PRKACB	P22694	909
WASF1	PRKACG	P22612	909
WASF1	BAIAP2	Q9UQB8	864
WASF1	NCK1	P16333	846

IntAct

178 interactions, top by confidence:

A	B	Type	Score
ABI2	BRK1	psi-mi:“MI:0915”(physical association)	0.910
ABI2	CYFIP1	psi-mi:“MI:0915”(physical association)	0.870
NCK2	WASF1	psi-mi:“MI:0915”(physical association)	0.800
BAIAP2	YWHAQ	psi-mi:“MI:0914”(association)	0.740
BRK1	HSBP1	psi-mi:“MI:0914”(association)	0.740
NCKAP1	YWHAH	psi-mi:“MI:0914”(association)	0.730
WASF1	ABI3	psi-mi:“MI:0915”(physical association)	0.670
WASF1	BAIAP2	psi-mi:“MI:0915”(physical association)	0.660
NCK2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.640
WASF1	PFN1	psi-mi:“MI:0915”(physical association)	0.640
WASF1	CYFIP1	psi-mi:“MI:0914”(association)	0.640
BRK1	CYFIP1	psi-mi:“MI:0914”(association)	0.640

BioGRID (145): TRIP10 (Two-hybrid), IFT20 (Two-hybrid), WASF1 (Affinity Capture-MS), WASF1 (Affinity Capture-MS), WASF1 (Affinity Capture-MS), WASF1 (Affinity Capture-MS), FNBP1L (Co-fractionation), TRIP10 (Co-fractionation), WASF1 (Co-fractionation), WASF1 (Co-fractionation), WASF1 (Co-fractionation), WASF1 (Co-fractionation), WASF1 (Co-fractionation), WASF1 (Affinity Capture-MS), RAC1 (Affinity Capture-Western)

ESM2 similar proteins: A0JP43, A1YEW9, A2D4U8, A2D5N1, A2D671, A2T6K9, A8T6P4, B8AE37, F6QRE9, G3V9A7, O60238, P48785, P79149, Q0IIJ3, Q0P6D6, Q15170, Q15361, Q15390, Q2KIJ9, Q3T013, Q3ULM0, Q3ZBJ9, Q4V7L5, Q5H9J7, Q5NVG8, Q5PPP3, Q5PR69, Q5RFN3, Q5W0A0, Q66HD8, Q67XL4, Q6K678, Q86X53, Q8BP27, Q8BPM6, Q8C627, Q8N4S0, Q8R5H6, Q91W45, Q921P9

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

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
SRC	up-regulates	WASF1	phosphorylation
WASF1	“form complex”	“WRC complex”	binding
BAIAP2	up-regulates	WASF1	binding
SRGAP3	up-regulates	WASF1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 115 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	15	59.5×	4e-21
Activation of BAD and translocation to mitochondria	6	57.1×	2e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	50.4×	4e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	50.4×	4e-08
Parasite infection	10	43.3×	1e-12
Leishmania phagocytosis	10	43.3×	1e-12
Activation of BH3-only proteins	6	37.2×	3e-07
FCGR3A-mediated phagocytosis	15	35.1×	2e-17

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of lamellipodium assembly	7	40.1×	2e-07
Rac protein signal transduction	6	32.1×	7e-06
positive regulation of actin filament polymerization	10	31.5×	6e-10
regulation of actin filament polymerization	5	27.7×	2e-04
lamellipodium assembly	6	25.3×	3e-05
actin filament polymerization	5	22.9×	4e-04
protein targeting	5	17.4×	6e-04
positive regulation of stress fiber assembly	5	14.9×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	4
Uncertain significance	97
Likely benign	20
Benign	1

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
2506296	NM_003931.3(WASF1):c.493dup (p.Met165fs)	Pathogenic
2627587	NM_003931.3(WASF1):c.262G>T (p.Glu88Ter)	Pathogenic
3255117	NM_003931.3(WASF1):c.1473del (p.Pro492fs)	Pathogenic
4686772	NM_003931.3(WASF1):c.481T>C (p.Trp161Arg)	Pathogenic
4819775	NM_003931.3(WASF1):c.1429del (p.Gln477fs)	Pathogenic
561980	NM_003931.3(WASF1):c.1516C>T (p.Arg506Ter)	Pathogenic
561981	NM_003931.3(WASF1):c.1558C>T (p.Gln520Ter)	Pathogenic
561982	NM_003931.3(WASF1):c.1482delinsGCCAGG (p.Ile494fs)	Pathogenic
1314809	NM_003931.3(WASF1):c.1319C>T (p.Ser440Leu)	Likely pathogenic
1342385	NM_003931.3(WASF1):c.1466C>G (p.Ser489Ter)	Likely pathogenic
3373368	NM_003931.3(WASF1):c.902C>G (p.Thr301Arg)	Likely pathogenic
4796709	NM_003931.3(WASF1):c.1422del (p.Pro475fs)	Likely pathogenic

SpliceAI

2087 predictions. Top by Δscore:

Variant	Effect	Δscore
6:110101679:T:C	acceptor_gain	1.0000
6:110103373:CATA:C	donor_loss	1.0000
6:110103374:ATAC:A	donor_loss	1.0000
6:110103375:TA:T	donor_loss	1.0000
6:110103376:A:C	donor_loss	1.0000
6:110103377:CCT:C	donor_loss	1.0000
6:110103555:GGT:G	acceptor_gain	1.0000
6:110103556:GT:G	acceptor_gain	1.0000
6:110103558:C:CC	acceptor_gain	1.0000
6:110103559:T:C	acceptor_loss	1.0000
6:110105443:T:TA	donor_gain	1.0000
6:110105454:A:AC	donor_gain	1.0000
6:110105577:CTG:C	acceptor_gain	1.0000
6:110105580:C:CC	acceptor_gain	1.0000
6:110105594:T:TC	acceptor_gain	1.0000
6:110107072:AATAC:A	donor_loss	1.0000
6:110107073:ATAC:A	donor_loss	1.0000
6:110107074:TACCT:T	donor_loss	1.0000
6:110107076:CCTT:C	donor_gain	1.0000
6:110107085:T:TA	donor_gain	1.0000
6:110107097:T:TA	donor_gain	1.0000
6:110107104:AT:A	donor_gain	1.0000
6:110107190:CATCT:C	acceptor_gain	1.0000
6:110107191:ATCT:A	acceptor_gain	1.0000
6:110107193:CT:C	acceptor_gain	1.0000
6:110107195:C:CC	acceptor_gain	1.0000
6:110107200:A:AC	acceptor_gain	1.0000
6:110107200:A:C	acceptor_gain	1.0000
6:110107202:A:AC	acceptor_gain	1.0000
6:110107202:A:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000124871 (6:110168633 A>G), RS1000154908 (6:110147944 G>A), RS1000225595 (6:110146827 T>C), RS1000235217 (6:110147616 T>C), RS1000241176 (6:110141153 G>C), RS1000308694 (6:110163066 A>G), RS1000337718 (6:110121454 CAG>C), RS1000354611 (6:110174806 T>C), RS1000440200 (6:110154469 T>C,G), RS1000447274 (6:110129373 A>G), RS1000496431 (6:110181589 T>G), RS1000535275 (6:110138308 G>C), RS1000570545 (6:110115219 A>G), RS1000609352 (6:110142442 T>C), RS1000624165 (6:110179773 C>A)

Disease associations

OMIM: gene MIM:605035 | disease phenotypes: MIM:618707

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with absent language and variable seizures	Strong	Autosomal dominant
neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (4): neurodevelopmental disorder with absent language and variable seizures (MONDO:0032876), intellectual disability (MONDO:0001071), hereditary ataxia (MONDO:0100309), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Hereditary ataxia (Orphanet:183518), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000520	Proptosis
HP:0000582	Upslanted palpebral fissure
HP:0000592	Blue sclerae
HP:0000750	Delayed speech and language development
HP:0000957	Cafe-au-lait spot
HP:0001182	Tapered finger
HP:0001250	Seizure
HP:0001290	Generalized hypotonia
HP:0001382	Joint hypermobility
HP:0001763	Pes planus
HP:0002119	Ventriculomegaly
HP:0002136	Broad-based gait
HP:0002376	Developmental regression
HP:0002816	Genu recurvatum
HP:0003186	Inverted nipples
HP:0005643	Short 3rd toe
HP:0006610	Wide intermamillary distance
HP:0007663	Reduced visual acuity
HP:0008093	Short 4th toe
HP:0010864	Severe intellectual disability
HP:0011800	Midface retrusion
HP:0011968	Feeding difficulties
HP:0012450	Chronic constipation
HP:0025336	Delayed ability to sit
HP:0031936	Delayed ability to walk
HP:0100716	Self-injurious behavior

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C531684	Hereditary spinal ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
trichostatin A	affects cotreatment, decreases expression	3
Air Pollutants	decreases expression, increases abundance, affects cotreatment	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
Particulate Matter	decreases expression, increases abundance, affects expression	2
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	increases expression	1
methylselenic acid	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	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
dorsomorphin	decreases expression, affects cotreatment	1
Vorinostat	affects cotreatment, decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Vehicle Emissions	increases abundance, affects expression	1
Cadmium	decreases expression, increases abundance	1
Copper	affects binding, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Gallic Acid	decreases expression, increases expression	1
Hydrogen Peroxide	decreases expression	1
Ivermectin	decreases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Thiosemicarbazones	increases expression, affects binding	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TX78	HAP1 WASF1 (-) 1	Cancer cell line	Male
CVCL_TX79	HAP1 WASF1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders