WIPF2

Summary

WIPF2 (WAS/WASL interacting protein family member 2, HGNC:30923) is a protein-coding gene on chromosome 17q21.2, encoding WAS/WASL-interacting protein family member 2 (Q8TF74). Plays an active role in the formation of cell surface protrusions downstream of activated PDGFB receptors.

This gene encodes a WASP interacting protein (WIP)-related protein. It has been shown that this protein has a role in the WASP-mediated organization of the actin cytoskeleton and that this protein is a potential link between the activated platelet-derived growth factor receptor and the actin polymerization machinery.

Source: NCBI Gene 147179 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_133264

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30923
Approved symbol	WIPF2
Name	WAS/WASL interacting protein family member 2
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	WICH, WIRE
Ensembl gene	ENSG00000171475
Ensembl biotype	protein_coding
OMIM	609692
Entrez	147179

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 30 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000323571, ENST00000394103, ENST00000494757, ENST00000578304, ENST00000578623, ENST00000582781, ENST00000583130, ENST00000583268, ENST00000584296, ENST00000585043, ENST00000863500, ENST00000863501, ENST00000863502, ENST00000863503, ENST00000863504, ENST00000863505, ENST00000863506, ENST00000863507, ENST00000863508, ENST00000863509, ENST00000863510, ENST00000863511, ENST00000922625, ENST00000922626, ENST00000922627, ENST00000922628, ENST00000951231, ENST00000951232, ENST00000951233, ENST00000951234, ENST00000951235, ENST00000951236, ENST00000951237, ENST00000951238

RefSeq mRNA: 1 — MANE Select: NM_133264 NM_133264

CCDS: CCDS11364

Canonical transcript exons

ENST00000323571 — 8 exons

Exon	Start	End
ENSE00001245296	40278185	40284136
ENSE00002724054	40219304	40219492
ENSE00003469944	40277083	40277184
ENSE00003480380	40262525	40262641
ENSE00003496979	40260535	40260667
ENSE00003570866	40273790	40273999
ENSE00003596032	40256391	40256522
ENSE00003678832	40264490	40265146

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.1242 / max 157.9592, expressed in 1801 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160697	7.0143	1748
160698	4.3895	1643
160699	1.0876	654
160700	0.6950	403
160701	0.4942	221
160704	0.2844	94
208172	0.0811	37
160702	0.0781	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.40	gold quality
oocyte	CL:0000023	98.97	gold quality
buccal mucosa cell	CL:0002336	96.84	gold quality
frontal pole	UBERON:0002795	96.04	gold quality
lower lobe of lung	UBERON:0008949	94.69	gold quality
nipple	UBERON:0002030	94.37	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.03	gold quality
medial globus pallidus	UBERON:0002477	93.55	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.44	gold quality
olfactory bulb	UBERON:0002264	93.38	gold quality
cranial nerve II	UBERON:0000941	93.32	gold quality
paraflocculus	UBERON:0005351	93.31	gold quality
middle temporal gyrus	UBERON:0002771	93.08	gold quality
orbitofrontal cortex	UBERON:0004167	92.93	gold quality
globus pallidus	UBERON:0001875	92.84	gold quality
upper leg skin	UBERON:0004262	92.75	gold quality
ventral tegmental area	UBERON:0002691	92.67	gold quality
middle frontal gyrus	UBERON:0002702	92.23	gold quality
inferior vagus X ganglion	UBERON:0005363	92.22	gold quality
superior vestibular nucleus	UBERON:0007227	92.03	gold quality
parietal lobe	UBERON:0001872	92.00	gold quality
pylorus	UBERON:0001166	91.82	gold quality
mucosa of urinary bladder	UBERON:0001259	91.47	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.42	gold quality
postcentral gyrus	UBERON:0002581	91.36	gold quality
entorhinal cortex	UBERON:0002728	91.35	gold quality
type B pancreatic cell	CL:0000169	91.30	gold quality
medulla oblongata	UBERON:0001896	91.27	gold quality
CA1 field of hippocampus	UBERON:0003881	91.16	gold quality
subthalamic nucleus	UBERON:0001906	91.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

190 targeting WIPF2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-1236-3P	99.94	68.04	1695

Literature-anchored findings (GeneRIF, showing 7)

• The WASP-binding protein WIRE has a role in the regulation of the actin filament system downstream of the platelet-derived growth factor receptor (PMID:12213210)
• Data indicate that the reduced vimentin expression in response to EPHB4, WIPF2 and MTHFD2 silencing was observed at mRNA and protein levels. (PMID:23295955)
• results support a role for MAP1 proteins in promoting efficient retrograde trafficking of HIV-1 by stimulating the formation of stable microtubules and mediating the association of HIV-1 cores with microtubules. (PMID:25505242)
• 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)
• Overall, the authors demonstrate the active role of the Arp2/3 complex and WIPF2 in mediating the internalization of Aspergillus fumigatus conidia into human airway epithelial cells. (PMID:30792969)
• RP5-1120P11.3 promotes hepatocellular carcinoma development via the miR-196b-5p-WIPF2 axis. (PMID:31299165)
• WIPF2 promotes Shigella flexneri actin-based motility and cell-to-cell spread. (PMID:31414511)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	wipf2b	ENSDARG00000006712
danio_rerio	wipf2a	ENSDARG00000045298
mus_musculus	Wipf2	ENSMUSG00000038013
rattus_norvegicus	Wipf2	ENSRNOG00000027849

Paralogs (2): WIPF1 (ENSG00000115935), WIPF3 (ENSG00000122574)

Protein

Protein identifiers

WAS/WASL-interacting protein family member 2 — Q8TF74 (reviewed: Q8TF74)

Alternative names: WASP-interacting protein-related protein, WIP- and CR16-homologous protein, WIP-related protein

All UniProt accessions (5): A8MWR2, Q8TF74, J3KSA3, J3QKM5, J3QQS0

UniProt curated annotations — full annotation on UniProt →

Function. Plays an active role in the formation of cell surface protrusions downstream of activated PDGFB receptors. Plays an important role in actin-microspike formation through cooperation with WASL. May cooperate with WASP and WASL to induce mobilization and reorganization of the actin filament system.

Subunit / interactions. Interacts with WASL and WASP, and this interaction results in cytoplasmic relocation of these two proteins along actin filaments. Interacts with NCK2 resulting in the localization to sites of focal adhesions. No interaction was seen with WASF2 and WASF3.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Expressed mainly in brain, colon, lung and stomach (at protein level). Ubiquitously expressed, with high expression in brain, kidney, lung, and placenta.

Miscellaneous. Access to the profilin-binding site is masked in the full-length protein.

Similarity. Belongs to the verprolin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TF74-1	1	yes
Q8TF74-2	2

RefSeq proteins (1): NP_573571* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003124	WH2_dom	Domain

Pfam: PF02205

UniProt features (16 total): compositionally biased region 7, region of interest 4, chain 1, domain 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TF74-F1	60.28	0.04

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): 37

Function

Pathways and Gene Ontology

Reactome pathways

6 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-9013409	RHOJ GTPase cycle
R-HSA-9664422	FCGR3A-mediated phagocytosis

MSigDB gene sets: 168 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, MORF_MSH3, MORF_ATRX, CTATGCA_MIR153, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GTGCCTT_MIR506, BLALOCK_ALZHEIMERS_DISEASE_UP, ACATTCC_MIR1_MIR206, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, GOMF_ACTIN_BINDING, BASAKI_YBX1_TARGETS_DN, MORF_MT4, TGCCTTA_MIR124A, AGCTCCT_MIR28, SCHLOSSER_SERUM_RESPONSE_UP

GO Biological Process (0):

GO Molecular Function (2): actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (3): cytosol (GO:0005829), cytoskeleton (GO:0005856), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	3
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	2
cytoskeletal protein binding	1
binding	1
cytoplasm	1
intracellular membraneless organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1066 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WIPF2	WASL	O00401	811
WIPF2	ENAH	Q8N8S7	654
WIPF2	WASF1	Q92558	641
WIPF2	DNM1	Q05193	571
WIPF2	DNMBP	Q6XZF7	550
WIPF2	WAS	P42768	549
WIPF2	PFN4	Q8NHR9	547
WIPF2	AMPH	P49418	546
WIPF2	CCDC32	Q9BV29	506
WIPF2	C3orf18	Q9UK00	475
WIPF2	CTTNBP2NL	Q9P2B4	469
WIPF2	CDC42	P21181	466
WIPF2	BIN1	O00499	464
WIPF2	MRPL45	Q9BRJ2	459
WIPF2	FNBP1L	Q5T0N5	458

IntAct

48 interactions, top by confidence:

A	B	Type	Score
WIPF2	GRB2	psi-mi:“MI:0915”(physical association)	0.890
WASL	WIPF2	psi-mi:“MI:0915”(physical association)	0.850
WIPF2	WASL	psi-mi:“MI:0914”(association)	0.850
WASL	WIPF3	psi-mi:“MI:0914”(association)	0.740
PACSIN2	COBL	psi-mi:“MI:0914”(association)	0.740
NCK1	WASL	psi-mi:“MI:0914”(association)	0.740
GRB2	WIPF3	psi-mi:“MI:0914”(association)	0.730
SORBS3	WIPF2	psi-mi:“MI:0915”(physical association)	0.670
NCK2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.640
SNX9	WASL	psi-mi:“MI:0914”(association)	0.640
TVP23A	WIPF2	psi-mi:“MI:0915”(physical association)	0.560
GRB2	ARHGEF35	psi-mi:“MI:0914”(association)	0.530
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
NCK1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
WIPF2	WWOX	psi-mi:“MI:0915”(physical association)	0.400
WAS	WIPF2	psi-mi:“MI:0915”(physical association)	0.370
NCK1	APBB2	psi-mi:“MI:0914”(association)	0.350
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
PACSIN2	COBL	psi-mi:“MI:0914”(association)	0.350
ARHGAP27	MCRIP1	psi-mi:“MI:0914”(association)	0.350
CEP192	WASL	psi-mi:“MI:0914”(association)	0.350

BioGRID (71): WIPF2 (Affinity Capture-MS), WIPF2 (Affinity Capture-MS), WIPF2 (Affinity Capture-MS), WIPF2 (Proximity Label-MS), WIPF2 (Affinity Capture-MS), WIPF2 (Affinity Capture-MS), WIPF2 (Affinity Capture-MS), WIPF2 (Affinity Capture-MS), WIPF2 (Affinity Capture-RNA), WIPF2 (Affinity Capture-MS), WIPF2 (Affinity Capture-MS), WIPF2 (Proximity Label-MS), WIPF2 (Two-hybrid), WIPF2 (Two-hybrid), WIPF2 (Two-hybrid)

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: A6NGB9, P0C7L0, Q6IN36, Q6PEV3, Q8K1I7, Q8TF74, Q9Z0G8, O43516, P37370, Q9P6R1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 27 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×	2e-08
FCGR3A-mediated phagocytosis	6	48.8×	2e-07
Regulation of actin dynamics for phagocytic cup formation	6	48.0×	2e-07
Clathrin-mediated endocytosis	6	22.2×	2e-05
Signaling by Rho GTPases	5	7.4×	7e-03
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	5	7.3×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
cell migration	5	11.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1966 predictions. Top by Δscore:

Variant	Effect	Δscore
17:40219556:G:T	donor_gain	1.0000
17:40256385:TTGCA:T	acceptor_loss	1.0000
17:40256390:G:GA	acceptor_loss	1.0000
17:40256390:GGT:G	acceptor_gain	1.0000
17:40256390:GGTAT:G	acceptor_gain	1.0000
17:40260664:GAGA:G	donor_gain	1.0000
17:40260666:GA:G	donor_gain	1.0000
17:40260668:G:GG	donor_gain	1.0000
17:40262649:A:G	donor_gain	1.0000
17:40273788:A:AG	acceptor_gain	1.0000
17:40273789:G:GG	acceptor_gain	1.0000
17:40277078:C:CA	acceptor_gain	1.0000
17:40277079:GCAGA:G	acceptor_loss	1.0000
17:40277080:CAGA:C	acceptor_loss	1.0000
17:40277081:A:AG	acceptor_gain	1.0000
17:40277081:AGAT:A	acceptor_gain	1.0000
17:40277081:AGATG:A	acceptor_loss	1.0000
17:40277082:G:GT	acceptor_gain	1.0000
17:40277082:G:T	acceptor_loss	1.0000
17:40277082:GA:G	acceptor_gain	1.0000
17:40277082:GAT:G	acceptor_gain	1.0000
17:40277082:GATG:G	acceptor_gain	1.0000
17:40277082:GATGA:G	acceptor_gain	1.0000
17:40277182:GAG:G	donor_gain	1.0000
17:40277183:AGG:A	donor_loss	1.0000
17:40277185:G:GG	donor_gain	1.0000
17:40277185:GT:G	donor_loss	1.0000
17:40277186:T:G	donor_loss	1.0000
17:40219438:G:GT	donor_gain	0.9900
17:40219450:GT:G	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000021599 (17:40223875 G>C), RS1000072420 (17:40238006 C>T), RS1000080665 (17:40230199 C>T), RS1000100781 (17:40272062 C>T), RS1000111218 (17:40223520 T>C), RS1000181236 (17:40242962 G>C), RS1000188167 (17:40226934 G>A,C), RS1000198952 (17:40266451 G>A), RS1000253333 (17:40278291 C>G,T), RS1000328016 (17:40233015 T>C), RS1000354007 (17:40253198 G>A), RS1000379437 (17:40259247 T>G), RS1000384295 (17:40232696 A>G), RS1000468496 (17:40259047 G>A,T), RS1000471730 (17:40226681 C>T)

Disease associations

OMIM: gene MIM:609692 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002279_42	PR interval in Tripanosoma cruzi seropositivity	9.000000e-07
GCST006988_118	Blond vs. brown/black hair color	3.000000e-08
GCST008916_85	Asthma	2.000000e-12
GCST009524_184	Household income (MTAG)	1.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval
EFO:0003924	hair color
EFO:0009695	household income

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	4
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	3
Tobacco Smoke Pollution	increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
trichostatin A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
eprenetapopt	affects reaction, affects expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	increases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Thiram	increases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1
Zinc Sulfate	increases expression	1

Clinical trials (associated diseases)

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