WIPF1

Summary

WIPF1 (WAS/WASL interacting protein family member 1, HGNC:12736) is a protein-coding gene on chromosome 2q31.1, encoding WAS/WASL-interacting protein family member 1 (O43516). Plays a role in the reorganization of the actin cytoskeleton.

This gene encodes a protein that plays an important role in the organization of the actin cytoskeleton. The encoded protein binds to a region of Wiskott-Aldrich syndrome protein that is frequently mutated in Wiskott-Aldrich syndrome, an X-linked recessive disorder. Impairment of the interaction between these two proteins may contribute to the disease. Two transcript variants encoding the same protein have been identified for this gene.

Source: NCBI Gene 7456 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Wiskott-Aldrich syndrome 2 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 9
• Clinical variants (ClinVar): 375 total — 6 pathogenic
• Phenotypes (HPO): 7
• MANE Select transcript: NM_001375834

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12736
Approved symbol	WIPF1
Name	WAS/WASL interacting protein family member 1
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	WIP
Ensembl gene	ENSG00000115935
Ensembl biotype	protein_coding
OMIM	602357
Entrez	7456

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 23 protein_coding, 12 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000272746, ENST00000359761, ENST00000392546, ENST00000392547, ENST00000409415, ENST00000409891, ENST00000410117, ENST00000436221, ENST00000455428, ENST00000467149, ENST00000469002, ENST00000470752, ENST00000480400, ENST00000487291, ENST00000488830, ENST00000490887, ENST00000679041, ENST00000698666, ENST00000698667, ENST00000698668, ENST00000698669, ENST00000698670, ENST00000698671, ENST00000698701, ENST00000698702, ENST00000698703, ENST00000856317, ENST00000856318, ENST00000856319, ENST00000856320, ENST00000856321, ENST00000856322, ENST00000856323, ENST00000856324, ENST00000856325, ENST00000923323, ENST00000942416

RefSeq mRNA: 10 — MANE Select: NM_001375834 NM_001077269, NM_001375832, NM_001375833, NM_001375834, NM_001375835, NM_001375836, NM_001375837, NM_001375838, NM_001375839, NM_003387

CCDS: CCDS2260, CCDS92900, CCDS92901

Canonical transcript exons

ENST00000679041 — 8 exons

Exon	Start	End
ENSE00000782466	174575204	174575380
ENSE00000782467	174581310	174581439
ENSE00001073352	174567070	174567183
ENSE00001380779	174571676	174572446
ENSE00001914254	174597601	174597804
ENSE00003477394	174585523	174585611
ENSE00003661476	174567861	174568073
ENSE00003904458	174559574	174562602

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 98.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 82.4819 / max 3111.0207, expressed in 1743 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31888	27.4408	1683
31884	21.8651	645
31883	17.0022	816
31887	12.0507	613
31872	0.5164	239
31886	0.5142	191
31870	0.5115	230
31875	0.4572	211
31873	0.4329	158
31874	0.4003	173

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	98.59	gold quality
monocyte	CL:0000576	98.33	gold quality
leukocyte	CL:0000738	98.31	gold quality
mononuclear cell	CL:0000842	98.31	gold quality
vermiform appendix	UBERON:0001154	97.91	gold quality
lymph node	UBERON:0000029	97.65	gold quality
bone marrow cell	CL:0002092	97.57	gold quality
trabecular bone tissue	UBERON:0002483	97.46	gold quality
granulocyte	CL:0000094	97.23	gold quality
periodontal ligament	UBERON:0008266	96.33	gold quality
bone marrow	UBERON:0002371	96.20	gold quality
caecum	UBERON:0001153	96.17	gold quality
tibia	UBERON:0000979	96.06	gold quality
inferior vagus X ganglion	UBERON:0005363	96.05	gold quality
superficial temporal artery	UBERON:0001614	95.91	gold quality
inferior olivary complex	UBERON:0002127	95.80	gold quality
spleen	UBERON:0002106	95.77	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.66	gold quality
layer of synovial tissue	UBERON:0007616	95.55	gold quality
epithelium of nasopharynx	UBERON:0001951	95.44	gold quality
nasopharynx	UBERON:0001728	95.43	gold quality
calcaneal tendon	UBERON:0003701	95.31	gold quality
colonic epithelium	UBERON:0000397	95.17	gold quality
spinal cord	UBERON:0002240	95.08	gold quality
gall bladder	UBERON:0002110	95.00	gold quality
parietal pleura	UBERON:0002400	94.87	gold quality
pleura	UBERON:0000977	94.83	gold quality
visceral pleura	UBERON:0002401	94.74	gold quality
tonsil	UBERON:0002372	94.70	gold quality
decidua	UBERON:0002450	94.68	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	285.34
E-GEOD-75367	yes	195.58
E-CURD-122	yes	47.29
E-MTAB-10287	yes	30.69
E-GEOD-135922	yes	25.75
E-CURD-46	yes	15.68
E-ANND-3	yes	14.66
E-MTAB-9543	yes	14.66
E-CURD-112	yes	4.26
E-MTAB-7606	no	649.99
E-HCAD-8	no	24.09
E-MTAB-10553	no	11.38
E-CURD-120	no	7.08
E-MTAB-5061	no	3.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP63

miRNA regulators (miRDB)

147 targeting WIPF1, 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-3163	100.00	77.23	8605
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-4283	100.00	66.42	2097
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478

Literature-anchored findings (GeneRIF, showing 31)

• show that the N-WASP EVH1 domain specifically binds a 25 residue motif from the WASP Interacting Protein (WIP) (PMID:12437929)
• X-linked thrombocytopenia caused by a mutation in the WAS gene that disrupts interaction with the (WASP)-interacting protein (WIP). (PMID:12591280)
• interactions of WASP and WIP are affected by two novel mutations that change the conformation of WASP and disrupt hydrogen bonding (PMID:15469902)
• Only in the presence of WASP-interacting protein (WIP) can human WASP suppress the growth defect of Saccharomyces cerevisiae las17Delta strain. (PMID:16488394)
• A 1.3 mD multiprotein complex consisting of WASp-interacting protein (WIP), Wiskott-Aldrich syndrome protein (WASp), actin, and myosin IIA formigg during NK cell activation was identified with a role in complex formation and NK cell activity regulation. (PMID:16606694)
• WASP-interacting protein stabilizes Wiskott-Aldrich syndrome protein(WASP) and suggest that it may also be important for its function (PMID:17213309)
• the WIP-WASP complex plays an important role in WASP stabilization and NFAT activation (PMID:17711847)
• that WASP and WASP-interacting protein (WIP) form a complex at the phagocytic cup and that the WASP.WIP complex plays a critical role in the phagocytic cup formation. (PMID:17890224)
• In this review, in addition to its WASP-independent functions, the role of WIP is to regulate the activity and stability of WASP and shuttle WASP to areas of actin assembly. (PMID:17949983)
• WIP is involved in lytic granule transport and is essential for regulation of Natural killer cell cytotoxic function (PMID:18258743)
• formin-binding protein 17 (FBP17) recruits WASP, WASP-interacting protein (WIP), and dynamin-2 to the plasma membrane and that this recruitment is necessary for the formation of podosomes and phagocytic cups. (PMID:19155218)
• Groups of colorectal cancer, breast cancer, and glioma patients with low expression of the WIPF1 co-expression module generally had a favorable prognosis. (PMID:19399471)
• The results suggest that some of the mutations in the WH1 domain cause the Wiskott-Aldrich syndrome syndrome in humans by perturbing the WASP-WIP complex formation. (PMID:19817875)
• These findings reveal WIP as a previously unreported regulator of neuronal maturation and synaptic activity (PMID:21810783)
• These findings indicate that WIP deficiency should be suspected in patients with features of WAS in whom WAS sequence and mRNA levels are normal. (PMID:22231303)
• WIP was shown to interact with various binding partners, including the signaling proteins Nck, CrkL and cortactin. (PMID:22837718)
• Data indicate the WASp-interacting protein (WIP)-Wiskott-Aldrich syndrome protein (WASp) interaction in the regulation of actin-dependent processes. (PMID:24962707)
• conclude that tyrosine phosphorylation of WIP is a crucial regulator of WASP stability and function as an actin-nucleation-promoting factor (PMID:25413351)
• Results suggest that local invasiveness of ameloblastoma is dependent upon the migratory potential of its tumour cells as defined by their distribution of cortactin, N-WASP and WIP in correlation with F-actin cytoskeletal dynamics. (PMID:26752341)
• Study provides evidence that WIP and WIRE contribute to breast cancer cell invasiveness through coordinated roles. WIP seems necessary for the assembly of invasive protrusions, whereas WIRE regulates their maturation, which leads to matrix degradation. (PMID:27009365)
• WIP deficiency should be considered as a cause for autosomal-recessive immunodeficiency (PMID:27742395)
• WIP controls tumor growth by boosting signals that stabilize the YAP/TAZ complex via a mechanism mediated by the endocytic/endosomal system. (PMID:27851961)
• the present study identifies the WIPF1 gene as having novel oncogenic functions and playing an important role in the invasiveness and aggressiveness of thyroid cancer when aberrantly up-regulated by the BRAF V600E/MAPK pathway through its promoter demethylation. (PMID:27863429)
• Knocking down WIP expression in A549 cells significantly reduced RhoA levels and WIP was found to interact with RhoA suggesting that WIP might be executing its function by regulating RhoA. (PMID:27939884)
• establish a new cancer stem cell signalling pathway downstream of mtp53 in which AKT2 regulates WIP and controls YAP/TAZ stability. (PMID:28166194)
• Crosstalk between WIP and Rho family GTPases. (PMID:29172947)
• WIP residues 454-456 are the major contributor to WASp affinity, and residues 449-451 were found to have the largest effect upon WASp ubiquitylation and, presumably, degradation. (PMID:29215267)
• Authors identified WIPF1 as an oncoprotein in PDAC and a direct target of miR-141/miR-200c. They also defined the miR-141/200c-WIPF1-YAP/TAZ as a novel signaling pathway that is involved in the regulation of the invasion and metastasis of human PDAC cells. (PMID:30041660)
• DNA Methylation-Mediated Modulation of Endocytosis as Potential Mechanism for Synaptic Function Regulation in Murine Inhibitory Cortical Interneurons. (PMID:32147726)
• PD-L1 promotes tumor growth and progression by activating WIP and beta-catenin signaling pathways and predicts poor prognosis in lung cancer. (PMID:32632098)
• The Disordered Cellular Multi-Tasker WIP and Its Protein-Protein Interactions: A Structural View. (PMID:32708183)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	wipf1a	ENSDARG00000104300
mus_musculus	Wipf1	ENSMUSG00000075284
rattus_norvegicus	Wipf1	ENSRNOG00000018406
drosophila_melanogaster	Vrp1	FBGN0243516
caenorhabditis_elegans		WBGENE00020094

Paralogs (2): WIPF3 (ENSG00000122574), WIPF2 (ENSG00000171475)

Protein

Protein identifiers

WAS/WASL-interacting protein family member 1 — O43516 (reviewed: O43516)

Alternative names: Protein PRPL-2, Wiskott-Aldrich syndrome protein-interacting protein

All UniProt accessions (6): O43516, A0A140VJZ9, A0A8V8TNJ8, C9JB04, C9JTB9, E9PB87

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the reorganization of the actin cytoskeleton. Contributes with NCK1 and GRB2 in the recruitment and activation of WASL. May participate in regulating the subcellular localization of WASL, resulting in the disassembly of stress fibers in favor of filopodia formation. Plays a role in the formation of cell ruffles. Plays an important role in the intracellular motility of vaccinia virus by functioning as an adapter for recruiting WASL to vaccinia virus.

Subunit / interactions. Binds to WAS, profilin and actin. Binds to WASL. Interacts with DBNL. Interacts with FNBP1L (via the SH3 domain).

Subcellular location. Cytoplasmic vesicle. Cytoplasm. Cytoskeleton. Cell projection. Ruffle.

Tissue specificity. Highly expressed in peripheral blood mononuclear cells, spleen, placenta, small intestine, colon and thymus. Lower expression in ovary, heart, brain, lung, liver, skeletal muscle, kidney, pancreas, prostate and testis.

Disease relevance. Wiskott-Aldrich syndrome 2 (WAS2) [MIM:614493] An immunodeficiency disorder characterized by eczema, thrombocytopenia, recurrent infections, defective T-cell proliferation, and impaired natural killer cell function. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Binds to WAS within the N-terminal region 170, at a site distinct from the CDC42-binding site.

Miscellaneous. Recruited to PIP5K-induced vesicle surfaces in the absence of functional WASL.

Similarity. Belongs to the verprolin family.

Isoforms (4)

UniProt ID	Names	Canonical?
O43516-1	1	yes
O43516-2	2
O43516-3	3
O43516-4	4

RefSeq proteins (10): NP_001070737, NP_001362761, NP_001362762, NP_001362763, NP_001362764, NP_001362765, NP_001362766, NP_001362767, NP_001362768, NP_003378 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003124	WH2_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR053099	WAS/WASL-interacting_domain	Family

Pfam: PF02205

UniProt features (38 total): compositionally biased region 14, modified residue 8, repeat 3, splice variant 3, sequence conflict 3, sequence variant 2, region of interest 2, chain 1, domain 1, helix 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2A41	X-RAY DIFFRACTION	2.6
9EZN	SOLUTION NMR
9EZO	SOLUTION NMR
9EZP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43516-F1	59.19	0.03

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 (8): 33, 125, 134, 142, 234, 340, 345, 350

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-5663213	RHO GTPases Activate WASPs and WAVEs
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9664422	FCGR3A-mediated phagocytosis

MSigDB gene sets: 304 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOCC_RUFFLE, CTATGCA_MIR153, GTGCCTT_MIR506, GOBP_PROTEIN_MATURATION, MORF_ZNF10, ONKEN_UVEAL_MELANOMA_UP, GOBP_ACTIN_FILAMENT_ORGANIZATION, ENGELMANN_CANCER_PROGENITORS_UP, WTGAAAT_UNKNOWN

GO Biological Process (6): actin polymerization or depolymerization (GO:0008154), actin filament-based movement (GO:0030048), response to other organism (GO:0051707), protein-containing complex assembly (GO:0065003), protein folding (GO:0006457), actin filament-based process (GO:0030029)

GO Molecular Function (6): actin binding (GO:0003779), profilin binding (GO:0005522), cytoskeletal adaptor activity (GO:0008093), SH3 domain binding (GO:0017124), protein folding chaperone (GO:0044183), protein binding (GO:0005515)

GO Cellular Component (8): ruffle (GO:0001726), cytosol (GO:0005829), actin filament (GO:0005884), actin cytoskeleton (GO:0015629), cytoplasmic vesicle (GO:0031410), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	2
Fcgamma receptor (FCGR) dependent phagocytosis	1
RHO GTPase Effectors	1
Leishmania phagocytosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cellular process	2
cytoskeletal protein binding	2
cytoplasm	2
actin filament organization	1
actin filament-based process	1
response to external biotic stimulus	1
biological process involved in interspecies interaction between organisms	1
cellular component assembly	1
protein-containing complex organization	1
protein maturation	1
protein binding	1
protein-macromolecule adaptor activity	1
protein domain specific binding	1
molecular_function	1
protein folding	1
binding	1
cell leading edge	1
plasma membrane bounded cell projection	1
actin cytoskeleton	1
polymeric cytoskeletal fiber	1
cytoskeleton	1
intracellular vesicle	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1424 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WIPF1	WASL	O00401	999
WIPF1	WAS	P42768	999
WIPF1	NCK1	P16333	997
WIPF1	CDC42	P21181	974
WIPF1	CTTN	Q14247	970
WIPF1	FNBP1L	Q5T0N5	954
WIPF1	HCLS1	P14317	954
WIPF1	GRB2	P29354	954
WIPF1	PFN1	P07737	896
WIPF1	DOCK8	Q8NF50	881
WIPF1	CRKL	P46109	860
WIPF1	VASP	P50552	842
WIPF1	CFL2	Q9Y281	842
WIPF1	CFL1	P23528	842
WIPF1	ACTR2	P61160	800

IntAct

98 interactions, top by confidence:

A	B	Type	Score
WAS	WIPF1	psi-mi:“MI:0915”(physical association)	0.970
WIPF1	WAS	psi-mi:“MI:0915”(physical association)	0.970
WIPF1	WAS	psi-mi:“MI:0403”(colocalization)	0.970
WIPF1	WASL	psi-mi:“MI:0915”(physical association)	0.920
WASL	WIPF1	psi-mi:“MI:0915”(physical association)	0.920

BioGRID (78): WIPF1 (Two-hybrid), WIPF1 (Two-hybrid), WASL (Two-hybrid), HOMER3 (Two-hybrid), SEC24C (Two-hybrid), ABI2 (Two-hybrid), FASTK (Two-hybrid), WWP2 (Two-hybrid), WIPF1 (Two-hybrid), WIPF1 (Affinity Capture-MS), WIPF1 (Two-hybrid), HOMER3 (Two-hybrid), WIPF1 (Affinity Capture-MS), WIPF1 (Affinity Capture-MS), WIPF1 (Affinity Capture-MS)

ESM2 similar proteins: A3LN86, A5DP36, A5DVD6, A6ZKU1, A7E8B6, A7TKW4, A7TRW3, C5DUF5, O13736, O36027, O43125, O43516, O60641, O76337, O94274, P0DJJ3, P15891, P32790, P37370, P38479, P42768, Q05140, Q0U4Z8, Q12446, Q2GS33, Q4P3H6, Q4P5N0, Q54NF8, Q55FT9, Q5ALV2, Q5BBL3, Q5R896, Q5RDL3, Q5TJ65, Q6BMF7, Q6BSP4, Q6CHN0, Q6IN36, Q6IZA3, Q6PEV3

Diamond homologs: O43516, Q6IN36, Q6PEV3, Q8K1I7, Q8TF74, Q9Z0G8, A6NGB9, P0C7L0, Q9P6R1

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
FKBP15	“up-regulates activity”	WIPF1	binding
WIPF1	up-regulates	Endocytosis
WIPF1	up-regulates	“Early Endosome”
WIPF1	“up-regulates activity”	WASL	binding
BTK	“up-regulates activity”	WIPF1	phosphorylation
PRKCQ	“up-regulates activity”	WIPF1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 32 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	6	82.8×	1e-08
FCGR3A-mediated phagocytosis	8	65.1×	6e-11
Regulation of actin dynamics for phagocytic cup formation	6	48.0×	2e-07
Signaling by Receptor Tyrosine Kinases	5	11.2×	2e-03
Viral Infection Pathways	5	6.7×	9e-03
Infectious disease	6	6.5×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of actin filament polymerization	5	61.2×	7e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	0
Uncertain significance	176
Likely benign	152
Benign	17

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
2821077	NM_001375834.1(WIPF1):c.587C>G (p.Ser196Ter)	Pathogenic
30266	NM_001375834.1(WIPF1):c.1301C>G (p.Ser434Ter)	Pathogenic
3691481	NM_001375834.1(WIPF1):c.373C>T (p.Arg125Ter)	Pathogenic
3728324	NM_001375834.1(WIPF1):c.284del (p.Gly95fs)	Pathogenic
4732404	NM_001375834.1(WIPF1):c.420del (p.Ser142fs)	Pathogenic
976496	NM_001375834.1(WIPF1):c.709C>T (p.Gln237Ter)	Pathogenic

SpliceAI

2215 predictions. Top by Δscore:

Variant	Effect	Δscore
2:174566278:T:TA	donor_gain	1.0000
2:174566290:A:AC	donor_gain	1.0000
2:174566291:C:CC	donor_gain	1.0000
2:174567068:A:AC	donor_gain	1.0000
2:174567068:ACT:A	donor_gain	1.0000
2:174567068:ACTC:A	donor_gain	1.0000
2:174567069:C:CA	donor_gain	1.0000
2:174567069:CT:C	donor_gain	1.0000
2:174567069:CTC:C	donor_gain	1.0000
2:174567069:CTCC:C	donor_gain	1.0000
2:174567069:CTCCG:C	donor_gain	1.0000
2:174567179:CTCAT:C	acceptor_gain	1.0000
2:174567181:CAT:C	acceptor_gain	1.0000
2:174567184:C:CC	acceptor_gain	1.0000
2:174572446:TC:T	acceptor_loss	1.0000
2:174572447:C:CC	acceptor_gain	1.0000
2:174572448:T:G	acceptor_loss	1.0000
2:174575198:CCTTA:C	donor_loss	1.0000
2:174575199:CTTA:C	donor_loss	1.0000
2:174575200:TTA:T	donor_loss	1.0000
2:174575201:TACCA:T	donor_loss	1.0000
2:174575381:C:CC	acceptor_gain	1.0000
2:174581308:A:AC	donor_gain	1.0000
2:174581308:ACTGT:A	donor_gain	1.0000
2:174581309:C:CT	donor_gain	1.0000
2:174581309:CTGTC:C	donor_gain	1.0000
2:174585518:CTCA:C	donor_loss	1.0000
2:174585519:TCACC:T	donor_loss	1.0000
2:174585520:CA:C	donor_loss	1.0000
2:174585521:A:AC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000012601 (2:174570814 T>C), RS1000032380 (2:174580107 C>T), RS1000044520 (2:174613821 A>C), RS1000064211 (2:174637268 A>C), RS1000070616 (2:174681728 G>GAC), RS1000099229 (2:174588705 AT>A), RS1000110813 (2:174672245 G>A), RS1000171102 (2:174655619 T>C), RS1000196890 (2:174643760 A>C,T), RS1000202399 (2:174624131 C>A), RS1000217652 (2:174600394 A>G), RS1000219576 (2:174662745 AC>A), RS1000243328 (2:174578051 A>G), RS1000311885 (2:174592050 A>G), RS1000363536 (2:174566354 A>G)

Disease associations

OMIM: gene MIM:602357 | disease phenotypes: MIM:277970, MIM:614493

GenCC curated gene-disease

Disease	Classification	Inheritance
Wiskott-Aldrich syndrome 2	Strong	Autosomal recessive
Wiskott-Aldrich syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Wiskott-Aldrich syndrome 2	Definitive	AR

Mondo (2): Wiskott-Aldrich syndrome 2 (MONDO:0013779), Wiskott-Aldrich syndrome (MONDO:0010518)

Orphanet (1): Wiskott-Aldrich syndrome (Orphanet:906)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000964	Eczematoid dermatitis
HP:0001873	Thrombocytopenia
HP:0002719	Recurrent infections
HP:0005415	Decreased CD8+ T cell proportion
HP:0012177	Abnormal natural killer cell physiology
HP:0031379	Abnormal T cell proliferation

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002827_3	Urate levels (BMI interaction)	1.000000e-07
GCST003818_71	Resting heart rate	5.000000e-10
GCST006061_94	Atrial fibrillation	2.000000e-19
GCST006061_95	Atrial fibrillation	6.000000e-20
GCST006414_70	Atrial fibrillation	6.000000e-18
GCST007096_184	Pulse pressure	2.000000e-09
GCST007099_239	Systolic blood pressure	4.000000e-08
GCST90002395_345	Mean platelet volume	1.000000e-13
GCST90002401_390	Platelet distribution width	6.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0007984	platelet component distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D014923	Wiskott-Aldrich Syndrome	C15.378.100.100.970; C15.378.243.750.605.900; C15.378.463.960; C15.378.553.546.605.900; C16.320.099.970; C16.320.322.937; C16.320.798.875; C20.673.627.900; C20.673.795.875

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	4
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Tretinoin	increases expression, decreases expression	3
methylmercuric chloride	decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	affects methylation, increases methylation	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
testosterone enanthate	affects expression	1
salinomycin	decreases expression	1
beta-lapachone	increases expression	1
cobaltous chloride	decreases expression	1
nickel chloride	decreases expression	1
ochratoxin A	decreases expression	1
aflatoxin B2	increases methylation	1
nickel sulfate	increases expression	1
4-aminophenylarsenoxide	decreases reaction, affects binding	1
di-n-butylphosphoric acid	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
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Troglitazone	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2P5	HAP1 WIPF1 (-) 1	Cancer cell line	Male
CVCL_E2P6	HAP1 WIPF1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01289847	PHASE4	COMPLETED	A Study to Find Out How Safe and Effective Gammaplex® is in Young People With Primary Immunodeficiency
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT00278954	PHASE3	COMPLETED	Efficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases.
NCT03837483	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study to Evaluate the Use of a Cryopreserved Formulation of OTL-103 in Subjects With Wiskott-Aldrich Syndrome
NCT00909363	PHASE2	TERMINATED	Thrombocytopenia and Bleeding in Wiskott-Aldrich Syndrome (WAS) Patients
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02512679	PHASE2	TERMINATED	Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells
NCT03019809	PHASE2	UNKNOWN	A Trial of Plerixafor/G-CSF as Additional Agents for Conditioning Before TCR Alpha/Beta Depleted HSCT in WAS Patients
NCT03333486	PHASE2	TERMINATED	Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer
NCT04371939	PHASE2	UNKNOWN	Efficacy and Safety of Romiplostim Versus Eltrombopag in the Treatment of Thrombocytopenia in Patients With Wiskott-Aldrich Syndrome
NCT00160355	PHASE1	COMPLETED	Haploidentical Hematopoietic Stem Cell Transplantation Patients With Wiskott-Aldrich Syndrome
NCT00774358	PHASE1	COMPLETED	Interleukin-2 Treatment for Wiskott-Aldrich Syndrome
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT00730314	PHASE1/PHASE2	COMPLETED	Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells
NCT00885833	PHASE1/PHASE2	COMPLETED	Study of Reduced Toxicity Myeloablative Conditioning Regimen for Wiskott-Aldrich Syndrome (WAS)
NCT01347242	PHASE1/PHASE2	COMPLETED	Gene Therapy for Wiskott-Aldrich Syndrome (WAS)
NCT01347346	PHASE1/PHASE2	COMPLETED	Gene Therapy for WAS
NCT01410825	PHASE1/PHASE2	COMPLETED	Pilot and Feasibility Study of Hematopoietic Stem Cell Gene Transfer for the Wiskott-Aldrich Syndrome
NCT01515462	PHASE1/PHASE2	COMPLETED	Gene Therapy for Wiskott-Aldrich Syndrome
NCT01852370	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT02333760	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Long Term Safety Follow up of Haematopoietic Stem Cell Gene Therapy for the Wiskott Aldrich Syndrome
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT00004341	Not specified	UNKNOWN	Study of Genetic and Molecular Defects in Primary Immunodeficiency Disorders
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT00006319	Not specified	UNKNOWN	Molecular and Clinical Studies of Primary Immunodeficiency Diseases
NCT01319851	Not specified	TERMINATED	Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
NCT01953016	Not specified	COMPLETED	Participation in a Research Registry for Immune Disorders
NCT02064933	Not specified	COMPLETED	Patients Treated for Wiskott-Aldrich Syndrome (WAS) Since 1990
NCT03198195	Not specified	UNKNOWN	Post-transplant Cyclophosphamide in Wiskott-Aldrich Syndrome
NCT03399461	Not specified	COMPLETED	Targeted Literature Review and Subject Interviews in Wiskott-Aldrich Syndrome (WAS)
NCT04350164	Not specified	COMPLETED	Romiplostim Treatment for Thrombocytopenia in Patients With Wiskott-Aldrich Syndrome.
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening