WBP1

Summary

WBP1 (WW domain binding protein 1, HGNC:12737) is a protein-coding gene on chromosome 2p13.1, encoding WW domain-binding protein 1 (Q96G27).

The globular WW domain, named for the conserved tryptophan residues in the protein motif present in various structural and regulatory proteins, is known to play a role in the mediation of protein-protein interactions. This gene encodes a ligand of the WW domain of the Yes kinase-associated protein. Readthrough transcription of the neighboring upstream gene, which encodes INO80 complex subunit B, into this gene generates a non-coding transcript.

Source: NCBI Gene 23559 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_012477

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12737
Approved symbol	WBP1
Name	WW domain binding protein 1
Location	2p13.1
Locus type	gene with protein product
Status	Approved
Aliases	WBP-1
Ensembl gene	ENSG00000239779
Ensembl biotype	protein_coding
OMIM	606961
Entrez	23559

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 11 protein_coding, 5 protein_coding_CDS_not_defined, 5 retained_intron

ENST00000233615, ENST00000393972, ENST00000409737, ENST00000428943, ENST00000464774, ENST00000466303, ENST00000466835, ENST00000470536, ENST00000473467, ENST00000474185, ENST00000484744, ENST00000490120, ENST00000492047, ENST00000494741, ENST00000891907, ENST00000891908, ENST00000926553, ENST00000926554, ENST00000926555, ENST00000926556, ENST00000926557

RefSeq mRNA: 1 — MANE Select: NM_012477 NM_012477

CCDS: CCDS1943

Canonical transcript exons

ENST00000233615 — 4 exons

Exon	Start	End
ENSE00001824575	74458438	74458671
ENSE00003482934	74459873	74460049
ENSE00003536264	74459643	74459745
ENSE00003843384	74460221	74460881

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 98.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.3890 / max 113.8635, expressed in 1802 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21028	20.3890	1802

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.94	gold quality
pituitary gland	UBERON:0000007	98.39	gold quality
amygdala	UBERON:0001876	98.31	gold quality
temporal lobe	UBERON:0001871	98.30	gold quality
nucleus accumbens	UBERON:0001882	98.18	gold quality
adenohypophysis	UBERON:0002196	98.17	gold quality
putamen	UBERON:0001874	98.15	gold quality
caudate nucleus	UBERON:0001873	98.09	gold quality
right adrenal gland cortex	UBERON:0035827	98.06	gold quality
Ammon’s horn	UBERON:0001954	98.04	gold quality
left lobe of thyroid gland	UBERON:0001120	98.03	gold quality
fundus of stomach	UBERON:0001160	98.00	gold quality
thyroid gland	UBERON:0002046	97.98	gold quality
prostate gland	UBERON:0002367	97.93	gold quality
right lobe of thyroid gland	UBERON:0001119	97.89	gold quality
substantia nigra	UBERON:0002038	97.88	gold quality
right adrenal gland	UBERON:0001233	97.85	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.80	gold quality
left ovary	UBERON:0002119	97.77	gold quality
left adrenal gland cortex	UBERON:0035825	97.68	gold quality
hypothalamus	UBERON:0001898	97.62	gold quality
anterior cingulate cortex	UBERON:0009835	97.49	gold quality
fallopian tube	UBERON:0003889	97.47	gold quality
left adrenal gland	UBERON:0001234	97.43	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.42	gold quality
brain	UBERON:0000955	97.40	gold quality
right frontal lobe	UBERON:0002810	97.39	gold quality
endocervix	UBERON:0000458	97.34	gold quality
ovary	UBERON:0000992	97.27	gold quality
body of stomach	UBERON:0001161	97.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF6

miRNA regulators (miRDB)

15 targeting WBP1, 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-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-1914-5P	97.83	66.21	807
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-6762-5P	96.55	64.62	972
HSA-MIR-6845-5P	96.55	64.65	969
HSA-MIR-4749-3P	96.40	66.24	798
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280

Literature-anchored findings (GeneRIF, showing 3)

• Mcl-1 is a determinant of cell fate, and ATF6 mediates apoptosis via specific suppression of Mcl-1 through up-regulation of WBP1 (PMID:21841196)
• The WW1 and WW2 domains of YAP2 recognize various PPXY motifs within WBP1 and WBP2 in a highly promiscuous and subtle manner. (PMID:21981024)
• miR-21 inhibits cardiac fibroblasts proliferation by inactivating the TGF-beta1/Smad2 signaling pathway via up-regulation of WWP-1. (PMID:28495464)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch73-290k24.6	ENSDARG00000092260
mus_musculus	Wbp1	ENSMUSG00000030035
rattus_norvegicus	Wbp1	ENSRNOG00000008720

Paralogs (2): PRR7 (ENSG00000131188), WBP1L (ENSG00000166272)

Protein

Protein identifiers

WW domain-binding protein 1 — Q96G27 (reviewed: Q96G27)

All UniProt accessions (5): Q96G27, A0A384P602, A8MX15, B8ZZ95, C9JLM6

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with NEDD4. Binds to the WW domain of YAP1, WWP1 and WWP2. Interacts with WWOX.

Tissue specificity. Expressed in most tissues but at significantly lower levels in placenta, lung, liver, and kidney.

Domain organisation. The PPxY motif 2 mediates interaction with WWOX. Both PPxY motifs mediate interaction with NEDD4.

RefSeq proteins (1): NP_036609* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021684	WBP1-like	Family
IPR051994	WW_domain-binding	Family

Pfam: PF11669

UniProt features (7 total): region of interest 2, short sequence motif 2, chain 1, compositionally biased region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1JMQ	SOLUTION NMR
1K5R	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96G27-F1	59.75	0.09

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (1):

Position	Phenotype
141	abolishes interaction with wwox.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 118 (showing top): RACCACAR_AML_Q6, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, GROSS_HYPOXIA_VIA_ELK3_UP, PIT1_Q6, TGGAAA_NFAT_Q4_01, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOMF_WW_DOMAIN_BINDING, chr2p13, BAKKER_FOXO3_TARGETS_DN, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_QTL_TRANS, CAMP_UP.V1_UP, ASH1L_TARGET_GENES, ATF6_TARGET_GENES, CEBPZ_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (2): WW domain binding (GO:0050699), protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein domain specific binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

428 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WBP1	WBP2	Q969T9	952
WBP1	VOPP1	Q96AW1	564
WBP1	TMEM218	A2RU14	560
WBP1	OGFOD2	Q6N063	553
WBP1	KIAA1191	Q96A73	517
WBP1	WWOX	Q9NZC7	489
WBP1	SHISAL1	Q3SXP7	452
WBP1	TMEM207	Q6UWW9	444
WBP1	CYYR1	Q96J86	434
WBP1	TMEM178A	Q8NBL3	359
WBP1	SHISA8	B8ZZ34	353
WBP1	FEZ2	Q9UHY8	349
WBP1	SHISA3	A0PJX4	345
WBP1	ACTR5	Q9H9F9	336
WBP1	SHISAL2A	Q6UWV7	310

IntAct

20 interactions, top by confidence:

A	B	Type	Score
WWOX	WBP1	psi-mi:“MI:0915”(physical association)	0.690
WBP1	WWOX	psi-mi:“MI:0915”(physical association)	0.690
YAP1	WBP1	psi-mi:“MI:0407”(direct interaction)	0.620
WBP1	YAP1	psi-mi:“MI:0407”(direct interaction)	0.620
EPN2	WBP1	psi-mi:“MI:0915”(physical association)	0.560
WBP1	SMCO4	psi-mi:“MI:0915”(physical association)	0.560
ZMYND10	WBP1	psi-mi:“MI:0915”(physical association)	0.560
WBP1	EXTL3	psi-mi:“MI:0914”(association)	0.530
WBP1	CACNA1A	psi-mi:“MI:0915”(physical association)	0.370
WBP1	HSPA12A	psi-mi:“MI:0914”(association)	0.350
WBP1	EPN2	psi-mi:“MI:0915”(physical association)	0.000
SMCO4	WBP1	psi-mi:“MI:0915”(physical association)	0.000
ZMYND10	WBP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (88): CIAO1 (Affinity Capture-MS), SLC39A11 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), ATP2B4 (Affinity Capture-MS), METTL9 (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS), LEMD3 (Affinity Capture-MS), HSPA12A (Affinity Capture-MS), ZDHHC13 (Affinity Capture-MS), NEDD4 (Affinity Capture-MS), ITCH (Affinity Capture-MS), NEDD4L (Affinity Capture-MS), WWP1 (Affinity Capture-MS), SYVN1 (Affinity Capture-MS), MMS19 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RQ45, A0A1B0GWB2, A2A9T0, A6QPA0, A7MCY6, D3ZFB6, E9PUL5, E9Q0B3, F5GYI3, F5H4A9, J3QNX5, O70142, P0C1G7, P81408, P97764, P98077, Q148V8, Q15654, Q2KI80, Q3SX26, Q3SZL6, Q4V9L6, Q5FVJ4, Q5FW56, Q5RAC1, Q5T7N3, Q6DG50, Q6PAJ3, Q6PJ61, Q6ZMQ8, Q6ZNR0, Q6ZRV2, Q75VX8, Q7Z6L0, Q86UK7, Q86VE0, Q8BGW2, Q8BRJ3, Q8BX43, Q8C0R7

Diamond homologs: P0C1G7, P97764, Q8BGW2, Q96G27, Q9NX94

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

939 predictions. Top by Δscore:

Variant	Effect	Δscore
2:74459741:CTGGT:C	donor_gain	1.0000
2:74459742:TGGT:T	donor_gain	1.0000
2:74459743:GGTG:G	donor_gain	1.0000
2:74459744:GT:G	donor_gain	1.0000
2:74459746:G:GG	donor_gain	1.0000
2:74459871:AGGGT:A	acceptor_loss	1.0000
2:74460045:CCTTC:C	donor_gain	1.0000
2:74460050:G:GG	donor_gain	1.0000
2:74458528:G:GA	donor_gain	0.9900
2:74459146:G:GT	donor_gain	0.9900
2:74459638:CGCA:C	acceptor_loss	0.9900
2:74459640:CAGCT:C	acceptor_loss	0.9900
2:74459641:A:AG	acceptor_gain	0.9900
2:74459641:A:T	acceptor_loss	0.9900
2:74459642:G:GG	acceptor_gain	0.9900
2:74459642:G:GT	acceptor_loss	0.9900
2:74459642:GCTTC:G	acceptor_gain	0.9900
2:74459746:G:C	donor_loss	0.9900
2:74459747:T:A	donor_loss	0.9900
2:74459870:CAG:C	acceptor_loss	0.9900
2:74459871:A:AG	acceptor_gain	0.9900
2:74459871:AG:A	acceptor_gain	0.9900
2:74459872:G:GA	acceptor_loss	0.9900
2:74459872:G:GG	acceptor_gain	0.9900
2:74459872:GG:G	acceptor_gain	0.9900
2:74460002:C:T	donor_gain	0.9900
2:74460046:CTTC:C	donor_gain	0.9900
2:74460047:TTC:T	donor_gain	0.9900
2:74460216:TGCA:T	acceptor_loss	0.9900
2:74460218:CA:C	acceptor_loss	0.9900

AlphaMissense

1728 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:74459875:T:C	F59L	0.999
2:74459877:C:A	F59L	0.999
2:74459877:C:G	F59L	0.999
2:74459878:T:A	W60R	0.999
2:74459878:T:C	W60R	0.999
2:74459887:T:A	W63R	0.999
2:74459887:T:C	W63R	0.999
2:74459908:A:C	S70R	0.999
2:74459910:C:A	S70R	0.999
2:74459910:C:G	S70R	0.999
2:74459742:T:A	W57R	0.998
2:74459742:T:C	W57R	0.998
2:74459745:T:A	W58R	0.997
2:74459745:T:C	W58R	0.997
2:74459876:T:C	F59S	0.997
2:74459685:T:A	C38S	0.996
2:74459686:G:C	C38S	0.996
2:74459911:T:C	C71R	0.996
2:74459686:G:A	C38Y	0.995
2:74459700:T:A	C43S	0.995
2:74459701:G:C	C43S	0.995
2:74459702:C:G	C43W	0.995
2:74459722:G:A	C50Y	0.995
2:74459723:C:G	C50W	0.995
2:74459655:T:A	C28S	0.994
2:74459656:G:C	C28S	0.994
2:74459694:G:T	G41C	0.994
2:74459703:T:A	C44S	0.994
2:74459704:G:A	C44Y	0.994
2:74459704:G:C	C44S	0.994

dbSNP variants (sampled 300 via entrez): RS1000448439 (2:74461214 G>C), RS1001347317 (2:74457113 C>T), RS1001842485 (2:74456842 T>C), RS1002341452 (2:74461041 A>C,T), RS1002445576 (2:74458181 C>T), RS1002997350 (2:74457021 C>T), RS1003855820 (2:74459451 A>T), RS1004309306 (2:74458131 G>A), RS1004525536 (2:74457652 C>G), RS1005337855 (2:74459383 A>G), RS1005349510 (2:74459002 G>A), RS1005783065 (2:74458443 T>G), RS1006534376 (2:74459738 G>A), RS1006910040 (2:74459056 C>G), RS1006964155 (2:74458786 T>A,G)

Disease associations

OMIM: gene MIM:606961 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression, affects cotreatment	4
afuresertib	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression, decreases reaction	1
beta-lapachone	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
ICG 001	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Coumestrol	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Nickel	decreases reaction, affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1
Vitamin K 3	affects expression	1

Clinical trials (associated diseases)

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