WIPF3

Summary

WIPF3 (WAS/WASL interacting protein family member 3, HGNC:22004) is a protein-coding gene on chromosome 7p14.3, encoding WAS/WASL-interacting protein family member 3 (A6NGB9). May be a regulator of cytoskeletal organization.

Predicted to enable alpha-tubulin binding activity and gamma-tubulin binding activity. Predicted to be involved in Arp2/3 complex-mediated actin nucleation; endosomal transport; and exocytosis. Predicted to be located in cytosol. Predicted to be part of WASH complex. Predicted to be active in early endosome; recycling endosome; and synapse.

Source: NCBI Gene 644150 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 101 total
• MANE Select transcript: NM_001080529

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22004
Approved symbol	WIPF3
Name	WAS/WASL interacting protein family member 3
Location	7p14.3
Locus type	gene with protein product
Status	Approved
Aliases	CR16, FLJ36931
Ensembl gene	ENSG00000122574
Ensembl biotype	protein_coding
OMIM	612432
Entrez	644150

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000242140, ENST00000409123, ENST00000869766

RefSeq mRNA: 2 — MANE Select: NM_001080529 NM_001080529, NM_001391973

CCDS: CCDS56472, CCDS94074

Canonical transcript exons

ENST00000242140 — 9 exons

Exon	Start	End
ENSE00000832167	29879009	29879140
ENSE00000832169	29888068	29888217
ENSE00000832170	29889306	29889407
ENSE00001189300	29875830	29875962
ENSE00001298746	29883850	29884593
ENSE00001580678	29914493	29917061
ENSE00001586812	29904286	29904362
ENSE00001587547	29834668	29834814
ENSE00003743159	29806508	29806678

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 96.99.

FANTOM5 (CAGE): breadth broad, TPM avg 6.1897 / max 283.2254, expressed in 561 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
77927	4.4168	501
77924	0.4379	187
204402	0.2050	104
77925	0.1664	75
77928	0.1649	71
77923	0.1614	90
77922	0.1563	71
77934	0.1320	70
77933	0.1207	62
77935	0.0688	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	96.99	gold quality
middle temporal gyrus	UBERON:0002771	96.70	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.43	gold quality
deltoid	UBERON:0001476	93.76	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.36	gold quality
vastus lateralis	UBERON:0001379	93.17	gold quality
left ovary	UBERON:0002119	92.98	gold quality
quadriceps femoris	UBERON:0001377	92.71	gold quality
entorhinal cortex	UBERON:0002728	92.45	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.41	gold quality
endothelial cell	CL:0000115	92.21	gold quality
saphenous vein	UBERON:0007318	92.15	gold quality
ovary	UBERON:0000992	91.97	gold quality
corpus epididymis	UBERON:0004359	91.91	gold quality
biceps brachii	UBERON:0001507	91.76	gold quality
skeletal muscle tissue	UBERON:0001134	91.75	gold quality
cortical plate	UBERON:0005343	91.71	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.33	gold quality
postcentral gyrus	UBERON:0002581	91.21	gold quality
ganglionic eminence	UBERON:0004023	90.98	gold quality
superior frontal gyrus	UBERON:0002661	90.95	gold quality
right ovary	UBERON:0002118	90.25	gold quality
Ammon’s horn	UBERON:0001954	90.23	gold quality
muscle tissue	UBERON:0002385	89.92	gold quality
parietal lobe	UBERON:0001872	89.88	gold quality
lateral globus pallidus	UBERON:0002476	89.81	gold quality
primary visual cortex	UBERON:0002436	89.24	gold quality
putamen	UBERON:0001874	89.20	gold quality
cardiac muscle of right atrium	UBERON:0003379	89.15	gold quality
ventricular zone	UBERON:0003053	89.14	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	31.40
E-GEOD-81608	yes	17.74
E-GEOD-93593	yes	7.02
E-ANND-3	yes	5.67
E-MTAB-7008	no	119.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

140 targeting WIPF3, 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-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-4682	100.00	68.89	1258
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4697-3P	99.89	67.09	1123

Literature-anchored findings (GeneRIF, showing 4)

• CR16 and N-WASP are suggested to play important roles in spermatogenesis (PMID:17573773)
• The expressions of the CR16 protein and mRNA decrease markedly in the testis of patients with idiopathic azoospermia. (PMID:21348202)
• These findings provide the basis for further functional investigations of the ITSN/CR16 complex that may play an important role in actin remodeling and cellular invasion. (PMID:28161632)
• Identification of ARMH4 and WIPF3 as human podocyte proteins with potential roles in immunomodulation and cytoskeletal dynamics. (PMID:36649229)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	wipf3	ENSDARG00000036245
mus_musculus	Wipf3	ENSMUSG00000086040
rattus_norvegicus	Wipf3	ENSRNOG00000009571

Paralogs (2): WIPF1 (ENSG00000115935), WIPF2 (ENSG00000171475)

Protein

Protein identifiers

WAS/WASL-interacting protein family member 3 — A6NGB9 (reviewed: A6NGB9)

Alternative names: Corticosteroids and regional expression protein 16 homolog

All UniProt accessions (2): A0A0A0MSG0, A6NGB9

UniProt curated annotations — full annotation on UniProt →

Function. May be a regulator of cytoskeletal organization. May have a role in spermatogenesis.

Subunit / interactions. Interacts with WASL, and monomeric and filamentous actin.

Subcellular location. Cytoplasm.

Domain organisation. The WH2 domain is found in a number of putative actin-binding proteins. The profilin-binding motif has been implicated in the interaction with profilin and SH3 domains. The KLKR motif is essential for G-actin binding and for actin polymerization.

Similarity. Belongs to the verprolin family.

RefSeq proteins (2): NP_001073998, NP_001378902 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003124	WH2_dom	Domain
IPR028290	WASH1	Family

Pfam: PF02205

UniProt features (26 total): compositionally biased region 12, short sequence motif 5, modified residue 4, region of interest 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NGB9-F1	60.57	0.05

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 (4): 46, 149, 202, 383

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: 111 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MALE_GAMETE_GENERATION, GOBP_EXOCYTOSIS, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_SECRETION, GOBP_ENDOCYTIC_RECYCLING, GOMF_ACTIN_BINDING, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_ARP2_3_COMPLEX_MEDIATED_ACTIN_NUCLEATION, GOBP_RETROGRADE_TRANSPORT_ENDOSOME_TO_GOLGI, CUI_TCF21_TARGETS_2_DN, VECCHI_GASTRIC_CANCER_EARLY_DN, GOBP_LOCALIZATION_WITHIN_MEMBRANE

GO Biological Process (6): exocytosis (GO:0006887), spermatogenesis (GO:0007283), cell differentiation (GO:0030154), endocytic recycling (GO:0032456), Arp2/3 complex-mediated actin nucleation (GO:0034314), retrograde transport, endosome to Golgi (GO:0042147)

GO Molecular Function (4): actin binding (GO:0003779), alpha-tubulin binding (GO:0043014), gamma-tubulin binding (GO:0043015), protein binding (GO:0005515)

GO Cellular Component (5): early endosome (GO:0005769), cytosol (GO:0005829), recycling endosome (GO:0055037), WASH complex (GO:0071203), cytoplasm (GO:0005737)

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
endosomal transport	2
tubulin binding	2
endosome	2
cytoplasm	2
cellular anatomical structure	2
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
vesicle-mediated transport to the plasma membrane	1
actin nucleation	1
intercellular transport	1
cytosolic transport	1
cytoskeletal protein binding	1
binding	1
protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

774 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WIPF3	WASL	O00401	934
WIPF3	WAS	P42768	796
WIPF3	NCK1	P16333	596
WIPF3	ACTR2	P61160	564
WIPF3	FAM170B	A6NMN3	563
WIPF3	ITSN1	Q15811	553
WIPF3	VASP	P50552	492
WIPF3	NEB	P20929	491
WIPF3	CFL2	Q9Y281	466
WIPF3	CFL1	P23528	463
WIPF3	ARMH3	Q5T2E6	444
WIPF3	CDC42	P21181	435
WIPF3	HFM1	A2PYH4	413
WIPF3	BLOC1S2	Q6QNY1	410
WIPF3	MITD1	Q8WV92	402

IntAct

15 interactions, top by confidence:

A	B	Type	Score
WASL	WIPF3	psi-mi:“MI:0914”(association)	0.740
GRB2	WIPF3	psi-mi:“MI:0914”(association)	0.730
NCK2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.640
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
ACTB	ENAH	psi-mi:“MI:0914”(association)	0.350
ACTG1	ENAH	psi-mi:“MI:0914”(association)	0.350
WIPF3	WASL	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (32): WIPF3 (Affinity Capture-MS), WIPF3 (Affinity Capture-MS), WIPF3 (Affinity Capture-MS), WIPF3 (Affinity Capture-MS), WIPF3 (Affinity Capture-MS), WIPF3 (Affinity Capture-MS), WIPF3 (Reconstituted Complex), WIPF3 (Affinity Capture-Western), ITSN1 (Affinity Capture-Western), ITSN2 (Affinity Capture-Western), WIPF3 (Affinity Capture-MS), WIPF3 (Two-hybrid), WIPF3 (Proximity Label-MS), WIPF3 (Proximity Label-MS), WIPF3 (Affinity Capture-MS)

ESM2 similar proteins: A1X283, A2AAY5, A2AI08, A2VDK6, A6NGB9, D3ZUI5, O62674, O62676, O70305, O75128, P0C7L0, Q03173, Q04584, Q0IIJ3, Q15942, Q3SZL6, Q3TC93, Q3UZA1, Q3ZBT0, Q4KM52, Q5BJU7, Q5NBX1, Q5NVG8, Q5R413, Q5SV85, Q5XHX2, Q62415, Q62523, Q6ZU35, Q80XA6, Q8BH43, Q8BM65, Q8CG79, Q8IZD4, Q8N3V7, Q8NFH8, Q8R5H6, Q8TD55, Q8VHI6, Q8WV28

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	90
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2076 predictions. Top by Δscore:

Variant	Effect	Δscore
7:29875959:GAGA:G	donor_gain	1.0000
7:29875961:GA:G	donor_gain	1.0000
7:29875963:G:GG	donor_gain	1.0000
7:29875967:G:GG	donor_gain	1.0000
7:29879005:A:AG	acceptor_gain	1.0000
7:29879005:AAAG:A	acceptor_gain	1.0000
7:29879007:A:AG	acceptor_gain	1.0000
7:29879007:A:C	acceptor_loss	1.0000
7:29879008:G:GG	acceptor_gain	1.0000
7:29879137:GCAG:G	donor_gain	1.0000
7:29879141:G:C	donor_loss	1.0000
7:29879141:G:GG	donor_gain	1.0000
7:29879142:T:A	donor_loss	1.0000
7:29888065:AAGG:A	acceptor_gain	1.0000
7:29888066:A:G	acceptor_gain	1.0000
7:29889293:C:CA	acceptor_gain	1.0000
7:29889297:T:TA	acceptor_gain	1.0000
7:29889299:T:TA	acceptor_gain	1.0000
7:29889300:GTGCA:G	acceptor_loss	1.0000
7:29889302:GCA:G	acceptor_loss	1.0000
7:29889303:CA:C	acceptor_loss	1.0000
7:29889304:A:AC	acceptor_loss	1.0000
7:29889304:A:AG	acceptor_gain	1.0000
7:29889304:AGAT:A	acceptor_gain	1.0000
7:29889305:G:A	acceptor_loss	1.0000
7:29889305:G:GA	acceptor_gain	1.0000
7:29889305:GA:G	acceptor_gain	1.0000
7:29889305:GAT:G	acceptor_gain	1.0000
7:29889305:GATG:G	acceptor_gain	1.0000
7:29889403:CAGAA:C	donor_gain	1.0000

AlphaMissense

3039 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:29875888:T:C	L50S	0.999
7:29875897:T:A	I53N	0.999
7:29875897:T:C	I53T	0.999
7:29875897:T:G	I53S	0.999
7:29875915:T:A	L59Q	0.999
7:29875915:T:C	L59P	0.999
7:29879111:T:C	L109S	0.999
7:29875885:T:C	L49P	0.998
7:29875939:A:C	D67A	0.998
7:29875944:A:C	S69R	0.998
7:29875946:T:A	S69R	0.998
7:29875946:T:G	S69R	0.998
7:29879089:T:C	F102L	0.998
7:29879090:T:C	F102S	0.998
7:29879090:T:G	F102C	0.998
7:29879091:T:A	F102L	0.998
7:29879091:T:G	F102L	0.998
7:29889323:T:C	F423L	0.998
7:29889324:T:C	F423S	0.998
7:29889325:C:A	F423L	0.998
7:29889325:C:G	F423L	0.998
7:29875885:T:A	L49Q	0.997
7:29875938:G:C	D67H	0.997
7:29875939:A:T	D67V	0.997
7:29879102:T:C	F106S	0.997
7:29889329:T:C	F425L	0.997
7:29889331:C:A	F425L	0.997
7:29889331:C:G	F425L	0.997
7:29875915:T:G	L59R	0.996
7:29875939:A:G	D67G	0.996

dbSNP variants (sampled 300 via entrez): RS1000006871 (7:29914508 C>A,T), RS1000017636 (7:29841676 G>A,T), RS1000017766 (7:29812938 A>G), RS1000046178 (7:29892970 C>T), RS1000077373 (7:29893305 T>A), RS1000148396 (7:29847063 T>C), RS1000167227 (7:29845310 A>G), RS1000202566 (7:29863279 A>C,G), RS1000212843 (7:29906618 C>G,T), RS1000219762 (7:29882107 C>G,T), RS1000253000 (7:29899688 C>A,T), RS1000281634 (7:29853188 C>A,T), RS1000298422 (7:29866882 T>C), RS1000303512 (7:29889658 C>G), RS1000313609 (7:29810101 C>G)

Disease associations

OMIM: gene MIM:612432 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001680_3	Corneal curvature	5.000000e-06
GCST004727_2	Facial emotion recognition	3.000000e-06
GCST004728_1	Facial emotion recognition (angry faces)	4.000000e-06
GCST004730_3	Facial emotion recognition (sad faces)	4.000000e-06
GCST006586_19	Urinary albumin excretion	4.000000e-12
GCST006979_343	Heel bone mineral density	3.000000e-13
GCST008790_29	Urinary albumin-to-creatinine ratio	5.000000e-18
GCST008791_15	Microalbuminuria	6.000000e-12
GCST008794_17	Urinary albumin-to-creatinine ratio	2.000000e-17
GCST009640_32	Urinary albumin-to-creatinine ratio	2.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004345	corneal topography
EFO:0008329	facial emotion recognition measurement
EFO:0004285	albuminuria
EFO:0009270	heel bone mineral density
EFO:0007778	urinary albumin to creatinine ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	3
Resveratrol	affects cotreatment, decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
2-palmitoylglycerol	increases expression	1
entinostat	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
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Copper	affects cotreatment, decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression, affects response to substance, increases expression	1
Malathion	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Thimerosal	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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