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ZPBP2

gene
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Also known as ZPBPLMGC41930

Summary

ZPBP2 (zona pellucida binding protein 2, HGNC:20678) is a protein-coding gene on chromosome 17q21.1, encoding Zona pellucida-binding protein 2 (Q6X784). Is implicated in sperm-oocyte interaction during fertilization.

Predicted to be involved in acrosome assembly and binding activity of sperm to zona pellucida. Predicted to act upstream of or within membrane lipid metabolic process and regulation of gene expression. Located in nucleus.

Source: NCBI Gene 124626 — RefSeq curated summary.

At a glance

  • GWAS associations: 32
  • Clinical variants (ClinVar): 36 total
  • MANE Select transcript: NM_199321

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:20678
Approved symbolZPBP2
Namezona pellucida binding protein 2
Location17q21.1
Locus typegene with protein product
StatusApproved
AliasesZPBPL, MGC41930
Ensembl geneENSG00000186075
Ensembl biotypeprotein_coding
OMIM608499
Entrez124626

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000348931, ENST00000377940, ENST00000583811, ENST00000584588

RefSeq mRNA: 2 — MANE Select: NM_199321 NM_198844, NM_199321

CCDS: CCDS11352, CCDS11353

Canonical transcript exons

ENST00000348931 — 8 exons

ExonStartEnd
ENSE000013328503987525439875434
ENSE000013328513987304439873126
ENSE000013328533987227039872488
ENSE000013328543987146439871625
ENSE000013328553987069439870819
ENSE000013328563987668239877896
ENSE000013771633986854939868614
ENSE000027060783986820239868406

Expression profiles

Bgee: expression breadth broad, 42 present calls, max score 98.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3052 / max 293.6563, expressed in 9 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter IDTPM avgSamples expressed
1606380.19906
1606400.09695
1606390.00934

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
spermCL:000001998.99gold quality
right testisUBERON:000453496.30gold quality
left testisUBERON:000453396.26gold quality
adult organismUBERON:000702394.36gold quality
testisUBERON:000047393.75gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047386.99gold quality
secondary oocyteCL:000065573.94gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099168.29gold quality
oocyteCL:000002366.59gold quality
cardiac muscle of right atriumUBERON:000337954.34gold quality
left ventricle myocardiumUBERON:000656654.23gold quality
kidney epitheliumUBERON:000481953.93gold quality
epithelial cell of pancreasCL:000008353.74gold quality
upper arm skinUBERON:000426353.52gold quality
pancreatic ductal cellCL:000207952.54silver quality
lymph nodeUBERON:000002950.71gold quality
myocardiumUBERON:000234950.25gold quality
vermiform appendixUBERON:000115449.49gold quality
cerebellar vermisUBERON:000472048.32gold quality
caecumUBERON:000115347.34gold quality
nasal cavity epitheliumUBERON:000538447.03gold quality
quadriceps femorisUBERON:000137746.79gold quality
tibialis anteriorUBERON:000138546.73silver quality
deltoidUBERON:000147646.37gold quality
ileal mucosaUBERON:000033146.10silver quality
vastus lateralisUBERON:000137945.40gold quality
sural nerveUBERON:001548845.39gold quality
granulocyteCL:000009445.14silver quality
layer of synovial tissueUBERON:000761643.55gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451143.37gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

ExperimentMarker?Max mean expression
E-GEOD-134144yes29.66
E-ANND-3yes3.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting ZPBP2, 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-30A-5P100.0076.313233
HSA-MIR-30B-5P100.0076.293248
HSA-MIR-30C-5P100.0076.293248
HSA-MIR-30D-5P100.0076.323233
HSA-MIR-30E-5P100.0076.323242
HSA-MIR-12118100.0065.881270
HSA-MIR-4795-3P100.0074.624024
HSA-MIR-5692A100.0074.406850
HSA-MIR-6891-5P99.9866.531372
HSA-MIR-3173-3P99.9866.491217
HSA-MIR-3692-3P99.9870.272139
HSA-MIR-520D-5P99.9873.344883
HSA-MIR-524-5P99.9873.434882
HSA-MIR-548AN99.9770.912817
HSA-MIR-4666A-3P99.9671.713434
HSA-MIR-767-5P99.9570.85993
HSA-MIR-144-3P99.9473.982698
HSA-MIR-7-1-3P99.9171.534384
HSA-MIR-7-2-3P99.9171.404394
HSA-MIR-10523-5P99.9169.222038
HSA-MIR-368699.9070.532432
HSA-MIR-95-5P99.8972.173973
HSA-MIR-137-3P99.8774.742401
HSA-MIR-5582-3P99.8672.484221
HSA-MIR-659-3P99.8570.691620
HSA-MIR-548AR-3P99.8571.263889
HSA-MIR-548AZ-3P99.8270.563549
HSA-MIR-442099.8270.081624
HSA-MIR-548BC99.8270.613524
HSA-MIR-548E-3P99.8270.593514

Literature-anchored findings (GeneRIF, showing 9)

  • Data show that loss of zona pellucida binding proteins 1 and 2 in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis. (PMID:17664285)
  • The disease-linked haplotype and putative causal DNA variants of ZPBP2/GSDMB/ORMDL3 locus via a combination of genetic and functional analyses, were identified. (PMID:19732864)
  • allele-specific transcriptional regulation of genes in the asthma-associated chromosomal region 17q12-q21; rs4795397 influences activity of ZPBP2 promoter in an allele-dependent fashion and leads to nucleosome repositioning on the asthma-associated allele; methylation of exon 1 of ZPBP2 masks the genetic effect on ZPBP2 promoter; ORMDL3 promoter is unmethylated (PMID:22271045)
  • Four additional susceptibility loci (IRF8, TMEM39A, IKZF3, and ZPBP2) for systemic lupus erythematosus were robustly established a multiethnic population (European, African American, Asian, Hispanic, Gullah, and Amerindian). (PMID:22464253)
  • The allele T of rs10852936 surrounding the IKZF3-ZPBP2 locus confers risk for early-onset psoriasis. (PMID:25620289)
  • The local genotype influences methylation levels at SLC22A5 and ZPBP2 promoters independently of the asthma status. Further studies are necessary to confirm the relationship between GSDMA-ZPBP2 and SLC22A5 methylation and asthma in females and males separately. (PMID:26671913)
  • modest changes (8-13%) in promoter methylation levels of ZPBP2 and GSDMA may cause substantial changes in RNA levels and allelic expression of ZPBP2 and ORMDL3 is mediated by DNA methylation (PMID:28241063)
  • Study of diurnal expression profiles of ZPBP2/Zpbp2, gasdermin B, and ORMDL3/Ormdl3 in human and mouse tissues revealed that Ormdl3 and Zpbp2 were controlled by the circadian clock in a tissue-specific fashion provided the first evidence that disease-associated genes Zpbp2 and Ormdl3 are regulated by circadian rhythms and the Zpbp2 region influences expression of the core clock gene Nr1d1. (PMID:31560728)
  • The Germ Cell-Specific Markers ZPBP2 and PGK2 in Testicular Biopsies Can Predict the Presence as well as the Quality of Sperm in Non-obstructive Azoospermia Patients. (PMID:33507524)

Cross-species orthologs

2 orthologs

OrganismSymbolGene ID
mus_musculusZpbp2ENSMUSG00000017195
rattus_norvegicusZpbp2ENSRNOG00000007255

Paralogs (1): ZPBP (ENSG00000042813)

Protein

Protein identifiers

Zona pellucida-binding protein 2 — Q6X784 (reviewed: Q6X784)

Alternative names: ZPBP-like protein

All UniProt accessions (3): Q6X784, J3KRM0, J3KSF6

UniProt curated annotations — full annotation on UniProt →

Function. Is implicated in sperm-oocyte interaction during fertilization.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Acrosome. Secreted.

Tissue specificity. Expressed specifically in testis.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the zona pellucida-binding protein Sp38 family.

Isoforms (2)

UniProt IDNamesCanonical?
Q6X784-11yes
Q6X784-22

RefSeq proteins (2): NP_942141, NP_955353* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR007110Ig-like_domDomain
IPR010857Sp38-bdFamily
IPR013783Ig-like_foldHomologous_superfamily
IPR048805ZPBP1/2_CDomain
IPR048806ZPBP1/2_NDomain

Pfam: PF07354, PF20626

UniProt features (12 total): sequence variant 5, glycosylation site 4, signal peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q6X784-F186.810.70

Functional residue map

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

Glycosylation sites (4): 87, 221, 257, 309

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 131 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_SINGLE_FERTILIZATION, AP1_01, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_PRODUCTION_OF_MOLECULAR_MEDIATOR_OF_IMMUNE_RESPONSE, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION, GOBP_MALE_GAMETE_GENERATION, GOBP_MEMBRANE_LIPID_CATABOLIC_PROCESS, COUP_01, GOBP_REGULATION_OF_IMMUNOGLOBULIN_PRODUCTION, AP1_Q4_01, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS

GO Biological Process (6): acrosome assembly (GO:0001675), negative regulation of immunoglobulin production (GO:0002638), sphingolipid metabolic process (GO:0006665), binding of sperm to zona pellucida (GO:0007339), circadian regulation of gene expression (GO:0032922), obsolete membrane lipid catabolic process (GO:0046466)

GO Molecular Function (0):

GO Cellular Component (7): acrosomal vesicle (GO:0001669), zona pellucida receptor complex (GO:0002199), extracellular region (GO:0005576), nucleus (GO:0005634), membrane (GO:0016020), cell body (GO:0044297), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure3
developmental process involved in reproduction1
spermatid development1
cellular component assembly involved in morphogenesis1
cellular process involved in reproduction in multicellular organism1
secretory granule organization1
organelle assembly1
immunoglobulin production1
regulation of immunoglobulin production1
negative regulation of production of molecular mediator of immune response1
lipid metabolic process1
sperm-egg recognition1
circadian rhythm1
regulation of gene expression1
secretory granule1
chaperonin-containing T-complex1
protein-containing complex1
intracellular membrane-bounded organelle1
cytoplasm1
intracellular vesicle1

Protein interactions and networks

STRING

830 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
ZPBP2GSDMBQ8TAX9954
ZPBP2ORMDL3Q8N138932
ZPBP2IKZF3Q9UKT9929
ZPBP2GRB7Q14451726
ZPBP2LRRC3CA6NJW4718
ZPBP2ACRBPQ8NEB7686
ZPBP2GSDMAQ96QA5650
ZPBP2CTCFP49711606
ZPBP2IKZF1Q13422582
ZPBP2PGAP3Q96FM1570
ZPBP2GRB10Q13322561
ZPBP2C10orf120Q5SQS8465
ZPBP2MAN2B2Q9Y2E5459
ZPBP2ADAM32Q8TC27457
ZPBP2DENND1BQ6P3S1452

IntAct

4 interactions, top by confidence:

ABTypeScore
ZPBP2CD80psi-mi:“MI:0915”(physical association)0.400
ZPBP2PPP1R1Apsi-mi:“MI:0914”(association)0.350
ZPBP2PALMpsi-mi:“MI:0914”(association)0.350

BioGRID (32): TUBB8 (Affinity Capture-MS), ZNF146 (Affinity Capture-MS), LRP11 (Affinity Capture-MS), OS9 (Affinity Capture-MS), NPTX1 (Affinity Capture-MS), PROS1 (Affinity Capture-MS), PPP1R1A (Affinity Capture-MS), CRELD2 (Affinity Capture-MS), FRAS1 (Affinity Capture-MS), PDF (Affinity Capture-MS), PPP1R1A (Affinity Capture-MS), ZNF146 (Affinity Capture-MS), NPTX1 (Affinity Capture-MS), OS9 (Affinity Capture-MS), IL17RA (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8Y4Y8, A0A2R8YFL7, A0A2R8YFM6, A0A8J1K1A4, A5D791, E7FKV8, O77726, O88393, P20239, P20783, P26342, P35054, P40200, P47984, Q03167, Q05996, Q08DT3, Q17R60, Q2Q0J1, Q3MHP9, Q3U0X8, Q3V1M1, Q4FZG8, Q4V7E2, Q5BK49, Q5SY80, Q5XI99, Q6DFV8, Q6WRH9, Q6WRI0, Q6X784, Q7TST5, Q80VH0, Q86WS3, Q8JIR8, Q8R1W8, Q925U0, Q95KG7, Q9D9J7, Q9ET62

Diamond homologs: Q29108, Q62522, Q6PVW7, Q6Q2W4, Q6X782, Q6X784, Q6X786, Q9BS86

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance30
Likely benign2
Benign2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1532 predictions. Top by Δscore:

VariantEffectΔscore
17:39868274:G:GTdonor_gain1.0000
17:39868404:G:GTdonor_gain1.0000
17:39870692:A:AGacceptor_gain1.0000
17:39870693:G:GGacceptor_gain1.0000
17:39870693:GAC:Gacceptor_gain1.0000
17:39871460:TTA:Tacceptor_loss1.0000
17:39871462:A:ACacceptor_loss1.0000
17:39871462:A:AGacceptor_gain1.0000
17:39871463:G:GGacceptor_gain1.0000
17:39871463:GGA:Gacceptor_gain1.0000
17:39871463:GGAA:Gacceptor_gain1.0000
17:39871606:A:Gdonor_gain1.0000
17:39871623:TTGG:Tdonor_loss1.0000
17:39871624:TGGTA:Tdonor_loss1.0000
17:39871626:G:GGdonor_gain1.0000
17:39871627:T:TCdonor_loss1.0000
17:39871628:AA:Adonor_loss1.0000
17:39873042:A:AGacceptor_gain1.0000
17:39873043:G:GGacceptor_gain1.0000
17:39875246:A:AGacceptor_gain1.0000
17:39875247:A:Gacceptor_gain1.0000
17:39875249:CTTA:Cacceptor_loss1.0000
17:39875250:TTA:Tacceptor_loss1.0000
17:39875252:A:AGacceptor_gain1.0000
17:39875252:AG:Aacceptor_gain1.0000
17:39875253:G:GCacceptor_gain1.0000
17:39875253:GG:Gacceptor_gain1.0000
17:39875253:GGC:Gacceptor_gain1.0000
17:39875253:GGCA:Gacceptor_gain1.0000
17:39875253:GGCAA:Gacceptor_gain1.0000

AlphaMissense

2244 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
17:39875389:T:CF282L0.989
17:39875391:T:AF282L0.989
17:39875391:T:GF282L0.989
17:39870791:G:CW72C0.982
17:39870791:G:TW72C0.982
17:39870789:T:AW72R0.976
17:39870789:T:CW72R0.976
17:39872482:T:CF207L0.973
17:39872484:T:AF207L0.973
17:39872484:T:GF207L0.973
17:39876702:T:CF304L0.970
17:39876704:T:AF304L0.970
17:39876704:T:GF304L0.970
17:39872311:T:CF150L0.969
17:39872313:T:AF150L0.969
17:39872313:T:GF150L0.969
17:39875390:T:GF282C0.968
17:39870723:A:CS50R0.966
17:39870725:T:AS50R0.966
17:39870725:T:GS50R0.966
17:39871538:T:GY107D0.963
17:39876705:A:CS305R0.962
17:39876707:T:AS305R0.962
17:39876707:T:GS305R0.962
17:39871500:T:CL94P0.961
17:39871514:T:CF99L0.961
17:39871516:T:AF99L0.961
17:39871516:T:GF99L0.961
17:39875350:A:CS269R0.959
17:39875352:T:AS269R0.959

dbSNP variants (sampled 300 via entrez): RS1000080399 (17:39869541 A>G), RS1000182739 (17:39875424 T>C), RS1000342523 (17:39869025 C>A), RS1000843575 (17:39869286 A>G), RS1001246067 (17:39876977 G>A), RS1001295170 (17:39877139 C>T), RS1001594097 (17:39876587 A>C), RS1001894030 (17:39866549 A>G), RS1002086182 (17:39872247 T>A), RS1002198553 (17:39878196 A>C,T), RS1002348451 (17:39872231 A>G), RS1002400919 (17:39872508 T>G), RS1002475815 (17:39866410 A>G), RS1002849896 (17:39867590 G>A), RS1003311572 (17:39867852 T>C)

Disease associations

OMIM: gene MIM:608499 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

32 associations (top):

StudyTraitp-value
GCST000624_15Ulcerative colitis3.000000e-08
GCST000733_2Primary biliary cholangitis2.000000e-09
GCST000879_10Crohn’s disease2.000000e-09
GCST000964_1Ulcerative colitis5.000000e-11
GCST001685_2Primary biliary cholangitis4.000000e-09
GCST001725_54Inflammatory bowel disease4.000000e-38
GCST002304_15Fractional exhaled nitric oxide (childhood)5.000000e-06
GCST002304_21Fractional exhaled nitric oxide (childhood)2.000000e-08
GCST003987_1Asthma1.000000e-63
GCST004131_33Inflammatory bowel disease2.000000e-26
GCST004132_116Crohn’s disease1.000000e-16
GCST004133_16Ulcerative colitis2.000000e-16
GCST004390_1Asthma4.000000e-12
GCST005213_4Asthma (childhood onset)4.000000e-26
GCST005537_31Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)6.000000e-30
GCST005581_15Primary biliary cirrhosis6.000000e-14
GCST006061_203Atrial fibrillation3.000000e-06
GCST006409_40Allergic rhinitis2.000000e-17
GCST006414_35Atrial fibrillation3.000000e-11
GCST006537_1Subcutaneous adipose tissue3.000000e-08
GCST006940_54Neurociticism2.000000e-08
GCST007036_5Primary biliary cholangitis4.000000e-12
GCST007266_5Adult asthma4.000000e-12
GCST007564_21Asthma or allergic disease (pleiotropy)4.000000e-17
GCST007994_23Asthma (age of onset)7.000000e-65
GCST007995_2Asthma (childhood onset)1.000000e-111
GCST008838_5Asthma (time to onset)2.000000e-16
GCST008916_21Asthma2.000000e-62
GCST009798_11Asthma1.000000e-65
GCST009876_9Systemic sclerosis9.000000e-06

EFO canonical traits (4, from GWAS)

EFO IDTrait name
EFO:0004267biliary liver cirrhosis
EFO:0005536nitric oxide exhalation measurement
EFO:0007660neuroticism measurement
EFO:0004847age at onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

ChemicalActions (top 5)PubMed papers
MT19c compounddecreases expression1
Resveratrolaffects cotreatment, decreases expression1
Benzo(a)pyreneaffects methylation1
Folic Aciddecreases expression1
Plant Extractsaffects cotreatment, decreases expression1
Valproic Acidincreases methylation1

Clinical trials (associated diseases)

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

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
v1.1.2
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot