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WBP2NL

gene
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Also known as FLJ26145MGC26816PAWPGRAMD7

Summary

WBP2NL (WBP2 N-terminal like, HGNC:28389) is a protein-coding gene on chromosome 22q13.2, encoding Postacrosomal sheath WW domain-binding protein (Q6ICG8). May play a role in meiotic resumption and pronuclear formation, mediated by a WW domain-signaling pathway during fertilization.

WBP2NL is a sperm-specific WW domain-binding protein that promotes meiotic resumption and pronuclear development during oocyte fertilization (Wu et al., 2007 [PubMed 17289678]).

Source: NCBI Gene 164684 — RefSeq curated summary.

At a glance

  • GWAS associations: 13
  • Clinical variants (ClinVar): 52 total
  • MANE Select transcript: NM_152613

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:28389
Approved symbolWBP2NL
NameWBP2 N-terminal like
Location22q13.2
Locus typegene with protein product
StatusApproved
AliasesFLJ26145, MGC26816, PAWP, GRAMD7
Ensembl geneENSG00000183066
Ensembl biotypeprotein_coding
OMIM610981
Entrez164684

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 2 protein_coding, 1 retained_intron

ENST00000328823, ENST00000329620, ENST00000412113, ENST00000436265, ENST00000445185, ENST00000461730, ENST00000470812, ENST00000475341, ENST00000487176, ENST00000943073

RefSeq mRNA: 1 — MANE Select: NM_152613 NM_152613

CCDS: CCDS14029

Canonical transcript exons

ENST00000328823 — 6 exons

ExonStartEnd
ENSE000013046104202676642028475
ENSE000013046434201966242019803
ENSE000013142334201931142019419
ENSE000034889414199878841998880
ENSE000035984374202000442020096
ENSE000036155614202224942022356

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 95.99.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8513 / max 41.9509, expressed in 386 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter IDTPM avgSamples expressed
1925500.8007377
1925490.03999
2094890.01073

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
left testisUBERON:000453395.99gold quality
right testisUBERON:000453495.45gold quality
testisUBERON:000047391.13gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047385.24gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099169.65gold quality
right uterine tubeUBERON:000130269.39gold quality
body of pancreasUBERON:000115069.07gold quality
cerebellar hemisphereUBERON:000224568.48gold quality
cerebellar cortexUBERON:000212968.41gold quality
right lobe of thyroid glandUBERON:000111968.17gold quality
adenohypophysisUBERON:000219668.16gold quality
right hemisphere of cerebellumUBERON:001489068.15gold quality
left lobe of thyroid glandUBERON:000112067.49gold quality
ventricular zoneUBERON:000305367.49gold quality
pancreasUBERON:000126467.11gold quality
thyroid glandUBERON:000204666.99gold quality
islet of LangerhansUBERON:000000666.76gold quality
left ovaryUBERON:000211966.76gold quality
monocyteCL:000057666.64gold quality
colonic epitheliumUBERON:000039766.49gold quality
leukocyteCL:000073866.44gold quality
cerebellumUBERON:000203766.40gold quality
C1 segment of cervical spinal cordUBERON:000646966.22gold quality
right ovaryUBERON:000211866.18gold quality
tibial nerveUBERON:000132365.99gold quality
ganglionic eminenceUBERON:000402365.83gold quality
pituitary glandUBERON:000000765.81gold quality
mucosa of transverse colonUBERON:000499165.19gold quality
left uterine tubeUBERON:000130364.40gold quality
right frontal lobeUBERON:000281064.39gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-ANND-3no4.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting WBP2NL, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3163100.0077.238605
HSA-LET-7A-3P100.0074.033932
HSA-LET-7B-3P100.0074.083913
HSA-LET-7F-1-3P100.0074.023928
HSA-MIR-98-3P100.0074.083907
HSA-MIR-1277-5P100.0073.955056
HSA-MIR-477599.9875.006394
HSA-MIR-806899.9873.852376
HSA-MIR-314899.9775.066478
HSA-MIR-3605-5P99.9667.12932
HSA-MIR-10523-5P99.9169.222038
HSA-MIR-130599.9171.433443
HSA-MIR-576-5P99.8470.462582
HSA-MIR-544A99.8468.661965
HSA-MIR-3150A-3P99.7664.441640
HSA-MIR-6763-5P99.7664.681767
HSA-MIR-3059-5P99.7069.932491
HSA-MIR-128399.6972.423009
HSA-MIR-3934-5P99.6764.04846
HSA-MIR-317599.6566.302031
HSA-MIR-4743-3P99.6268.122095
HSA-MIR-211399.5871.221521
HSA-MIR-3616-5P99.5567.02989
HSA-MIR-57399.5567.44955
HSA-MIR-7159-5P99.5372.122472
HSA-MIR-6833-5P99.5068.931161
HSA-MIR-203A-3P99.4970.562806
HSA-MIR-1213199.4868.721673
HSA-MIR-391199.3866.951087
HSA-MIR-6882-5P99.3571.131206

Literature-anchored findings (GeneRIF, showing 10)

  • Demonstrate significant correlations between sperm PAWP levels and both fertilization rates and normal embryonic development after intracytoplasmic sperm injection. (PMID:24907910)
  • WBP2NL might play roles as an anti-apoptotic factor or co-activator to promote breast cancer cell survival and proliferation. (PMID:25417742)
  • Data suggest that PAWP (WW domain-binding protein 2-like) from sperm (rather than PLCZ [phospholipase C zeta] from sperm) acts as the ‘sperm factor’ within the egg at fertilization and is involved in ’egg activation’ and embryogenesis. [REVIEW] (PMID:25722320)
  • Conclude that human PAWP is neither sufficient nor necessary for the Ca(2+) oscillations that initiate mammalian oocyte activation at fertilization. (PMID:26116451)
  • In male infertility, the absence of PLCZ1 alone is sufficient to prevent oocyte activation irrespective of the presence of PAWP. (PMID:26721930)
  • High fertilization (56.06%) and pregnancy (41.7%) rates accomplished in this study following ICSI-AOA indicated that expression profiles of PLCzeta, PAWP, and TR-KIT were low in globozoospermic individuals (PMID:27089467)
  • The value of PAWP and PLCzeta as indicators of sperm quality was studied. (PMID:28076980)
  • Taken into account that WBP2NL/PAWP gene and protein levels and distribution did not correlate with fertilization rates, this study questions the interest of WBP2NL/PAWP protein and gene expression analysis in sperm cells as a prognostic factor for the outcome of ICSI cycles (PMID:28444612)
  • PLCzeta and PAWP impairments may be one of the possible etiologies of decreased fertility in Oligoasthenoteratozoospermia (PMID:28954204)
  • PAWP/WBP2NL was present in all samples, and no significant differences were detected between patients with fertilization failure and donors in sequence variants or mean protein expression, or in the proportion of PAWP/WBP2NL-positive sperm. In conclusion, no clear association between PAWP/WBP2NL protein expression in sperm and fertilization outcome in ICSI were observed from this cohort. (PMID:29271520)

Cross-species orthologs

6 orthologs

OrganismSymbolGene ID
danio_reriowbp2nlENSDARG00000044852
mus_musculusWbp2nlENSMUSG00000022455
rattus_norvegicusWbp2nlENSRNOG00000008038
drosophila_melanogasterWbp2FBGN0036318
caenorhabditis_elegansWBGENE00008404
caenorhabditis_elegansWBGENE00015955

Paralogs (1): WBP2 (ENSG00000132471)

Protein

Protein identifiers

Postacrosomal sheath WW domain-binding protein — Q6ICG8 (reviewed: Q6ICG8)

Alternative names: WW domain-binding protein 2-like

All UniProt accessions (3): Q6ICG8, F8WCF8, F8WDR4

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in meiotic resumption and pronuclear formation, mediated by a WW domain-signaling pathway during fertilization.

Tissue specificity. Expressed in testis.

RefSeq proteins (1): NP_689826* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR004182GRAMDomain
IPR044852WBP2-likeFamily

Pfam: PF02893

UniProt features (22 total): repeat 10, sequence variant 4, region of interest 2, compositionally biased region 2, chain 1, domain 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q6ICG8-F163.880.29

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 93 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_SINGLE_FERTILIZATION, FXR_IR1_Q6, GCANCTGNY_MYOD_Q6, FOXO4_01, CAGCTG_AP4_Q5, E2F1DP1_01, E2F1DP2_01, GOBP_NUCLEUS_ORGANIZATION, HP1SITEFACTOR_Q6, GOBP_ORGANELLE_ASSEMBLY, PPAR_DR1_Q2, HFH1_01, GOBP_REGULATION_OF_CYTOSOLIC_CALCIUM_ION_CONCENTRATION, GOBP_MONOATOMIC_ION_HOMEOSTASIS

GO Biological Process (4): egg activation (GO:0007343), male pronucleus assembly (GO:0035039), positive regulation of DNA-templated transcription (GO:0045893), meiotic cell cycle (GO:0051321)

GO Molecular Function (4): transcription coactivator activity (GO:0003713), chromatin DNA binding (GO:0031490), WW domain binding (GO:0050699), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), perinuclear theca (GO:0033011), sperm flagellum (GO:0036126), sperm head (GO:0061827)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
single fertilization2
cell activation1
nucleus organization1
organelle assembly1
DNA-templated transcription1
regulation of DNA-templated transcription1
positive regulation of RNA biosynthetic process1
cell cycle1
sexual reproduction1
reproductive process1
meiotic nuclear division1
transcription coregulator activity1
positive regulation of DNA-templated transcription1
DNA binding1
chromatin binding1
protein domain specific binding1
binding1
intracellular membrane-bounded organelle1
cytoskeleton1
perinuclear region of cytoplasm1
9+2 motile cilium1
cellular anatomical structure1

Protein interactions and networks

STRING

824 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
WBP2NLPLCZ1Q86YW0808
WBP2NLGARIN2Q8N9W8575
WBP2NLSPATA16Q9BXB7537
WBP2NLACSBG2Q5FVE4525
WBP2NLDNAI3Q8IWG1495
WBP2NLTULP2O00295490
WBP2NLTMEM250H0YL14480
WBP2NLLVRNQ6Q4G3477
WBP2NLROPN1LQ96C74474
WBP2NLGALNTL5Q7Z4T8468
WBP2NLREDIC1Q86WS4464
WBP2NLRNF17Q9BXT8461
WBP2NLSLC9B1Q4ZJI4461
WBP2NLDMRT1Q9Y5R6460
WBP2NLC9orf43Q8TAL5451

IntAct

10 interactions, top by confidence:

ABTypeScore
WBP2NLFMR1psi-mi:“MI:0915”(physical association)0.560
WBP2NLLAMP2psi-mi:“MI:0915”(physical association)0.560
WBP2NLOTUD4psi-mi:“MI:0914”(association)0.530
WBP2NLACTBpsi-mi:“MI:0914”(association)0.350
WBP2NLFMR1psi-mi:“MI:0915”(physical association)0.000

BioGRID (24): FMR1 (Affinity Capture-MS), MGA (Affinity Capture-MS), ACTR5 (Affinity Capture-MS), PCGF6 (Affinity Capture-MS), INO80C (Affinity Capture-MS), OTUD4 (Affinity Capture-MS), ACTR5 (Affinity Capture-MS), INO80C (Affinity Capture-MS), OTUD4 (Affinity Capture-MS), PCGF6 (Affinity Capture-MS), MGA (Affinity Capture-MS), FMR1 (Affinity Capture-MS), WBP2NL (Two-hybrid), OTUD4 (Affinity Capture-MS), FMR1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M1NHK4, A3KFF6, A6H8J1, O49429, O80678, O80910, P12348, P55265, P94017, P97765, Q08B53, Q13434, Q32SG5, Q3T1I4, Q3TJZ6, Q3UMQ8, Q3UPH1, Q4R3M1, Q5F3N9, Q5FWT1, Q5R679, Q5XJA3, Q5Z8L1, Q66H68, Q6ICG8, Q6P870, Q7G6K7, Q7ZYB4, Q8AVN9, Q8LA32, Q8R478, Q8R4X3, Q93YP4, Q94JZ8, Q969T9, Q96M27, Q9C5P0, Q9C6S1, Q9D529, Q9FF15

Diamond homologs: A3KFF6, P97765, Q4R3M1, Q6ICG8, Q8R478, Q969T9, Q9D529, O14032

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance39
Likely benign7
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1377 predictions. Top by Δscore:

VariantEffectΔscore
22:41998968:G:Tdonor_gain1.0000
22:42001931:G:GTdonor_gain1.0000
22:42001977:G:GTdonor_gain1.0000
22:42019710:A:AGacceptor_gain1.0000
22:42019710:AT:Aacceptor_gain1.0000
22:42019711:T:Gacceptor_gain1.0000
22:42019711:T:TAacceptor_gain1.0000
22:42019718:ATTT:Aacceptor_gain1.0000
22:42019721:T:Aacceptor_gain1.0000
22:42019998:CCCCA:Cacceptor_loss1.0000
22:42019999:CCCA:Cacceptor_loss1.0000
22:42020000:CCAGG:Cacceptor_loss1.0000
22:42020001:CAGGT:Cacceptor_loss1.0000
22:42020003:G:Aacceptor_loss1.0000
22:42020003:GGT:Gacceptor_gain1.0000
22:42020093:GCTG:Gdonor_gain1.0000
22:42020094:CTGG:Cdonor_loss1.0000
22:42020095:TGGTA:Tdonor_loss1.0000
22:42020096:GGTA:Gdonor_loss1.0000
22:42020097:G:GGdonor_gain1.0000
22:42020097:G:Tdonor_loss1.0000
22:42020098:TAAG:Tdonor_loss1.0000
22:42026756:T:Gacceptor_gain1.0000
22:42026757:A:AGacceptor_gain1.0000
22:42026758:A:Gacceptor_gain1.0000
22:41998892:G:GTdonor_gain0.9900
22:41998892:G:Tdonor_gain0.9900
22:41998958:GCGA:Gdonor_gain0.9900
22:41998967:GGAC:Gdonor_gain0.9900
22:42001965:A:AGdonor_gain0.9900

AlphaMissense

1930 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
22:42019668:T:CF60L0.973
22:42019670:C:AF60L0.973
22:42019670:C:GF60L0.973
22:42020039:T:CF117L0.957
22:42020041:C:AF117L0.957
22:42020041:C:GF117L0.957
22:42020027:T:CF113L0.955
22:42020029:T:AF113L0.955
22:42020029:T:GF113L0.955
22:42019418:G:CR57P0.953
22:42020063:T:CF125L0.953
22:42020065:T:AF125L0.953
22:42020065:T:GF125L0.953
22:42019345:T:CF33L0.938
22:42019347:C:AF33L0.938
22:42019347:C:GF33L0.938
22:42019714:T:CM75T0.935
22:42019719:T:CF77L0.928
22:42019721:T:AF77L0.928
22:42019721:T:GF77L0.928
22:42020009:T:AW107R0.924
22:42020009:T:CW107R0.924
22:42019669:T:CF60S0.914
22:42019707:T:CF73L0.911
22:42019709:T:AF73L0.911
22:42019709:T:GF73L0.911
22:42019316:T:CL23S0.910
22:42020011:G:CW107C0.910
22:42020011:G:TW107C0.910
22:42019714:T:GM75R0.908

dbSNP variants (sampled 300 via entrez): RS1000035354 (22:42007827 C>T), RS1000038281 (22:42044177 A>G), RS1000147357 (22:42002420 C>T), RS1000227933 (22:42048279 G>A), RS1000258986 (22:42048557 C>A), RS1000324667 (22:42030593 A>G), RS1000326343 (22:42024423 G>A,T), RS1000368297 (22:42002660 G>A,T), RS1000379171 (22:42036936 G>A), RS1000380365 (22:42037204 T>G), RS1000483183 (22:42030985 G>T), RS1000503978 (22:42000020 C>T), RS1000545099 (22:42011303 C>T), RS1000577917 (22:42037083 A>G), RS1000592105 (22:42024130 G>A)

Disease associations

OMIM: gene MIM:610981 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

StudyTraitp-value
GCST001585_27Breast size5.000000e-07
GCST002539_95Schizophrenia2.000000e-09
GCST004364_23Intelligence3.000000e-10
GCST004364_5Intelligence3.000000e-10
GCST004521_160Autism spectrum disorder or schizophrenia3.000000e-08
GCST004521_244Autism spectrum disorder or schizophrenia4.000000e-09
GCST004616_176Platelet distribution width3.000000e-12
GCST006803_13Schizophrenia2.000000e-14
GCST006952_1Feeling tense3.000000e-08
GCST008030_4Estimated glomerular filtration rate4.000000e-08
GCST008030_6Estimated glomerular filtration rate9.000000e-06
GCST009212_16Isthmus-cingulate cortex volume5.000000e-08
GCST010002_83Refractive error2.000000e-27

EFO canonical traits (3, from GWAS)

EFO IDTrait name
EFO:0004337intelligence
EFO:0007984platelet component distribution width
EFO:0009596feeling tense measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

5 annotations.

VariantTypeLevelDrugsPhenotypes
rs739296Toxicity3codeineadverse events
rs739296Toxicity3oxycodoneadverse events
rs739296Toxicity3hydrocodoneadverse events
rs739296Toxicity3tramadoladverse events
rs9620007Toxicity3codeineadverse events

PharmGKB variants

4 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs5758550WBP2NL0.000
rs9620007WBP2NL30.001codeine
rs739296SEPTIN3, WBP2NL30.004hydrocodone;codeine;oxycodone;tramadol
rs1062753SEPTIN3, WBP2NL0.000

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

ChemicalActions (top 5)PubMed papers
Aflatoxin B1increases methylation2
triphenyl phosphateaffects expression1
CGP 52608affects binding, increases reaction1
Acetaminophendecreases expression1
Hydralazineaffects cotreatment, increases expression1
Malathiondecreases expression1
Valproic Acidaffects cotreatment, increases expression1
Permethrindecreases expression1

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

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