WAS (WASP actin nucleation promoting factor)

Gene

• Entrez ID: 7454
• Gene name: WASP actin nucleation promoting factor
• Gene symbol: WAS
• Synonyms: IMD2, SCNX, THC, THC1, WASP, WASPA
• Chromosome: X
• Chromosome location: Xp11.23
• Summary: The Wiskott-Aldrich syndrome (WAS) family of proteins share similar domain structure, and are involved in transduction of signals from receptors on the cell surface to the actin cytoskeleton. The presence of a number of different motifs suggests that they are regulated by a number of different stimuli, and interact with multiple proteins. Recent studies have demonstrated that these proteins, directly or indirectly, associate with the small GTPase, Cdc42, known to regulate formation of actin filaments, and the cytoskeletal organizing complex, Arp2/3. Wiskott-Aldrich syndrome is a rare, inherited, X-linked, recessive disease characterized by immune dysregulation and microthrombocytopenia, and is caused by mutations in the WAS gene. The WAS gene product is a cytoplasmic protein, expressed exclusively in hematopoietic cells, which show signalling and cytoskeletal abnormalities in WAS patients. A transcript variant arising as a result of alternative promoter usage, and containing a different 5` UTR sequence, has been described, however, its full-length nature is not known. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs132630268	G>A,C,T	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs132630269	C>T	Pathogenic	Coding sequence variant, missense variant
rs132630270	C>G	Pathogenic	Coding sequence variant, missense variant
rs132630271	C>A,T	Pathogenic	Coding sequence variant, synonymous variant, stop gained
rs132630272	T>C	Pathogenic	Coding sequence variant, missense variant
rs132630273	C>T	Pathogenic	Coding sequence variant, missense variant
rs132630274	T>C	Pathogenic	Coding sequence variant, missense variant
rs132630275	C>A,G	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs132630276	T>A	Pathogenic	Coding sequence variant, missense variant
rs139265251	G>A,C	Not-provided, pathogenic, benign	Coding sequence variant, missense variant
rs145040665	C>A,T	Conflicting-interpretations-of-pathogenicity, likely-benign	Missense variant, coding sequence variant
rs150520117	C>T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs193922412	ACCGCCACC>-,ACCGCCACCACCGCCACC	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Inframe deletion, coding sequence variant, inframe insertion
rs193922414	C>G,T	Likely-pathogenic	Missense variant, coding sequence variant, stop gained
rs193922415	C>T	Pathogenic	Coding sequence variant, stop gained
rs193922416	->C	Likely-pathogenic	Frameshift variant, coding sequence variant
rs368151220	C>A,T	Pathogenic	Synonymous variant, coding sequence variant, stop gained
rs387906716	T>C	Pathogenic	Missense variant, coding sequence variant
rs387906717	T>C	Pathogenic	Missense variant, coding sequence variant
rs587776742	A>T	Pathogenic	Missense variant, initiator codon variant
rs587776743	->ACGAGG	Pathogenic	Inframe insertion, coding sequence variant
rs587776744	G>-	Pathogenic	Frameshift variant, coding sequence variant
rs587776745	G>-	Pathogenic	Frameshift variant, coding sequence variant
rs781799471	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs782290433	G>A	Pathogenic	Coding sequence variant, missense variant
rs886039451	G>A,C	Likely-pathogenic, pathogenic	Intron variant
rs886041379	->C	Pathogenic	Frameshift variant, coding sequence variant
rs1057517845	G>A	Pathogenic	Splice donor variant
rs1057518633	->CCACCACC	Pathogenic	Frameshift variant, coding sequence variant
rs1057520700	G>A,C,T	Pathogenic	Splice donor variant
rs1064793292	->GGGAATGGACCAGCCCC	Pathogenic	Frameshift variant, coding sequence variant
rs1064793293	G>A	Pathogenic	Missense variant, coding sequence variant
rs1064793974	G>T	Pathogenic	Coding sequence variant, stop gained
rs1064794076	G>A	Pathogenic	Splice donor variant
rs1085307678	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs1557006239	G>A	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs1557006316	TACCT>AACCTGGCGCTGCCCCC	Likely-pathogenic	Inframe indel, coding sequence variant
rs1557006354	C>T	Pathogenic	Stop gained, coding sequence variant
rs1557006474	G>A	Likely-pathogenic	Stop gained, coding sequence variant
rs1557006672	C>T	Likely-pathogenic	Stop gained, coding sequence variant
rs1557007011	G>A	Pathogenic	Intron variant
rs1557007035	C>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1557007123	C>T	Pathogenic	Intron variant, stop gained, coding sequence variant
rs1557007165	C>-	Pathogenic	Intron variant, frameshift variant, coding sequence variant
rs1557007312	->G	Pathogenic	Frameshift variant, coding sequence variant
rs1569493877	T>A	Pathogenic	Splice donor variant
rs1569494025	G>-	Pathogenic	Coding sequence variant, frameshift variant, intron variant
rs1602176146	CAGAGCCTCGCCAGAGAAGACAAGGGCAGAAAGCACCATGAGTGGGGGCCCAATGGGAGGAAGGCCCGGGGGCCGAGGAGCACCAGCGGTTCAGCAGAACATACCCTCCACCCTCCTCCAGGACCACGAGAACCAGCGACTCTTTGAGATGCTTGGACGAAAATGCTTGGTGAGCTGGGGATCTCCTGCCCCCGCCCCGTCCCC>-	Pathogenic	Splice donor variant, 5 prime UTR variant, initiator codon variant, intron variant
rs1602176222	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs1602176299	AC>-	Pathogenic	Coding sequence variant, frameshift variant
rs1602177243	G>T	Pathogenic	Coding sequence variant, stop gained
rs1602177562	GC>-	Pathogenic	Coding sequence variant, frameshift variant
rs1602177733	T>G	Pathogenic	Splice donor variant
rs1602178087	G>A	Pathogenic	Splice acceptor variant
rs1602178165	C>T	Pathogenic	Coding sequence variant, stop gained
rs1602178184	TAGCC>-	Pathogenic	Coding sequence variant, frameshift variant
rs1602178267	G>A	Pathogenic	Intron variant
rs1602178800	A>G	Pathogenic	Splice acceptor variant
rs1602178952	G>TT	Pathogenic	Coding sequence variant, frameshift variant
rs1602179000	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1602179794	CGGCAGGGAATTCAGCTGAACAAGGTGAGGACAGGCAGGATGGAGGATTGGGGGTCTAGGACTCTGGGGTGTCCCGTCTAAGTCAGGATACTGGGGGGCTGAGGCCAGGACTGAGGAGAGTGCCAGGCCTTAGGGATTCAGTGATAGGGTTGAAAGGTTGGTGGGAAGCCTTGAAGGGGACTGGAGTGTGTGGGAGAGAAAATATTGATGGAGGGGCGGGGAGAAATGCTCCTTTCCCAGGCCCTAAGCCCTCTG	Pathogenic	Coding sequence variant, splice acceptor variant, intron variant, splice donor variant
rs1602179810	AGGTGAGGACA>-	Pathogenic	Coding sequence variant, splice donor variant, intron variant
rs1602180020	A>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1602180058	C>T	Pathogenic	Coding sequence variant, stop gained

Transcription factors

Transcription factor	Regulation	Reference
ETS1	Unknown	10066431
MYB	Unknown	10066431
SP1	Unknown	10066431
SPI1	Unknown	10066431

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002625	Process	Regulation of T cell antigen processing and presentation	IMP	22804504
GO:0003779	Function	Actin binding	IEA
GO:0005515	Function	Protein binding	IPI	8892607, 9405671, 9422512, 9660763, 10202051, 12029088, 12235133, 12591280, 15169891, 15361624, 16488394, 17213309, 17242350, 18650809, 19234535, 19487689, 19805221, 20936779, 21516116, 21988832, 22252508, 25416956, 25502805, 31515488, 32296183
GO:0005634	Component	Nucleus	IDA	20574068, 29925947
GO:0005829	Component	Cytosol	IDA	8625410
GO:0005829	Component	Cytosol	TAS
GO:0005884	Component	Actin filament	IBA	21873635
GO:0005884	Component	Actin filament	IDA	8625410
GO:0005886	Component	Plasma membrane	IDA
GO:0005911	Component	Cell-cell junction	IEA
GO:0006952	Process	Defense response	TAS	8069912
GO:0006955	Process	Immune response	IMP	8069912
GO:0007266	Process	Rho protein signal transduction	IMP	8625410
GO:0007596	Process	Blood coagulation	TAS	8069912
GO:0008064	Process	Regulation of actin polymerization or depolymerization	IMP	8625410
GO:0008154	Process	Actin polymerization or depolymerization	TAS	8625410
GO:0008544	Process	Epidermis development	TAS	8069912
GO:0010591	Process	Regulation of lamellipodium assembly	IGI	8625410
GO:0012506	Component	Vesicle membrane	IEA
GO:0015629	Component	Actin cytoskeleton	TAS	8625410
GO:0016197	Process	Endosomal transport	IEA
GO:0017124	Function	SH3 domain binding	IPI	8892607, 19798448
GO:0019901	Function	Protein kinase binding	IPI	8892607
GO:0030041	Process	Actin filament polymerization	IDA	29925947
GO:0030048	Process	Actin filament-based movement	IBA	21873635
GO:0030695	Function	GTPase regulator activity	TAS	8625410
GO:0031267	Function	Small GTPase binding	IPI	8625410, 10724160
GO:0032488	Process	Cdc42 protein signal transduction	IMP	8625410
GO:0035861	Component	Site of double-strand break	IDA	29925947
GO:0038096	Process	Fc-gamma receptor signaling pathway involved in phagocytosis	TAS
GO:0042110	Process	T cell activation	IEA
GO:0042802	Function	Identical protein binding	IPI	10724160, 12769847, 18650809
GO:0043274	Function	Phospholipase binding	IPI	8892607
GO:0045335	Component	Phagocytic vesicle	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	20574068
GO:0050790	Process	Regulation of catalytic activity	IEA
GO:0050852	Process	T cell receptor signaling pathway	TAS
GO:0051492	Process	Regulation of stress fiber assembly	IGI	8625410
GO:0051497	Process	Negative regulation of stress fiber assembly	IMP	8625410
GO:0065003	Process	Protein-containing complex assembly	TAS	8625410
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:0071346	Process	Cellular response to interferon-gamma	IEA
GO:1905168	Process	Positive regulation of double-strand break repair via homologous recombination	IDA	29925947
GO:2000146	Process	Negative regulation of cell motility	IMP	22804504
GO:2000601	Process	Positive regulation of Arp2/3 complex-mediated actin nucleation	IEA
GO:2001032	Process	Regulation of double-strand break repair via nonhomologous end joining	IDA	29925947

Other IDs

• MIM: 300392
• HGNC: 12731
• e!Ensembl: ENSG00000015285

Protein

• UniProt ID: P42768
• Protein name: Wiskott-Aldrich syndrome protein (WASp)
• Protein function: Effector protein for Rho-type GTPases that regulates actin filament reorganization via its interaction with the Arp2/3 complex (PubMed:12235133, PubMed:12769847, PubMed:16275905). Important for efficient actin polymerization (PubMed:8625410, PubMed:12235133, PubMed:16275905). Possible regulator of lymphocyte and platelet function (PubMed:9405671). Mediates actin filament reorganization and the formation of actin pedestals upon infection by pathogenic bacteria (PubMed:18650809). In addition to its role in the cytoplasmic cytoskeleton, also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA (PubMed:20574068). Promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs) (PubMed:29925947).
• PDB: 1CEE, 1EJ5, 1T84, 2A3Z, 2K42, 2OT0
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00568	WH1	36 → 145	WH1 domain	Domain
  PF00786	PBD	237 → 296	P21-Rho-binding domain	Domain
  PF02205	WH2	427 → 454	WH2 motif	Family

• Sequence:

  MSGGPMGGRPGGRGAPAVQQNIPSTLLQDHENQRLFEMLGRKCLTLATAVVQLYLALPPG
  AEHWTKEHCGAVCFVKDNPQKSYFIRLYGLQAGRLLWEQELYSQLVYSTPTPFFHTFAGD
  DCQAGLNFADEDEAQAFRALVQEKIQKRNQRQSGDRRQLPPPPTPANEERRGGLPPLPLH
  PGGDQGGPPVGPLSLGLATVDIQNPDITSSRYRGLPAPGPSPADKKRSGKKKISKADIGA
  PSGFKHVSHVGWDPQNGFDVNNLDPDLRSLFSRAGISEAQLTDAETSKLIYDFIEDQGGL
  EAVRQEMRRQEPLPPPPPPSRGGNQLPRPPIVGGNKGRSGPLPPVPLGIAPPPPTPRGPP
  PPGRGGPPPPPPPATGRSGPLPPPPPGAGGPPMPPPPPPPPPPPSSGNGPAPPPLPPALV
  PAGGLAPGGGRGALLDQIRQGIQLNKTPGAPESSALQPPPQSSEGLVGALMHVMQKRSRA
  IHSSDEGEDQAGDEDEDDEWDD

• Sequence length: 502