ZP3

Summary

ZP3 (zona pellucida glycoprotein 3, HGNC:13189) is a protein-coding gene on chromosome 7q11.23, encoding Zona pellucida sperm-binding protein 3 (P21754). Component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy.

The zona pellucida is an extracellular matrix that surrounds the oocyte and early embryo. It is composed primarily of three or four glycoproteins with various functions during fertilization and preimplantation development. The protein encoded by this gene is a structural component of the zona pellucida and functions in primary binding and induction of the sperm acrosome reaction. The nascent protein contains a N-terminal signal peptide sequence, a conserved ZP domain, a C-terminal consensus furin cleavage site, and a transmembrane domain. It is hypothesized that furin cleavage results in release of the mature protein from the plasma membrane for subsequent incorporation into the zona pellucida matrix. However, the requirement for furin cleavage in this process remains controversial based on mouse studies. A variation in the last exon of this gene has previously served as the basis for an additional ZP3 locus; however, sequence and literature review reveals that there is only one full-length ZP3 locus in the human genome. Another locus encoding a bipartite transcript designated POMZP3 contains a duplication of the last four exons of ZP3, including the above described variation, and maps closely to this gene.

Source: NCBI Gene 7784 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oocyte maturation defect 3 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 122 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 3
• MANE Select transcript: NM_001110354

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13189
Approved symbol	ZP3
Name	zona pellucida glycoprotein 3
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Aliases	ZP3-424, ZP3-372, ZPC
Ensembl gene	ENSG00000188372
Ensembl biotype	protein_coding
OMIM	182889
Entrez	7784

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000336517, ENST00000394857, ENST00000394860, ENST00000416245, ENST00000466960, ENST00000467555, ENST00000479793

RefSeq mRNA: 2 — MANE Select: NM_001110354 NM_001110354, NM_007155

CCDS: CCDS47618, CCDS5586

Canonical transcript exons

ENST00000394857 — 8 exons

Exon	Start	End
ENSE00000918820	76429515	76429633
ENSE00000918822	76433470	76433647
ENSE00001519824	76424950	76425276
ENSE00002523186	76434038	76434155
ENSE00003642301	76440250	76440341
ENSE00003668067	76432927	76433030
ENSE00003668475	76440475	76440611
ENSE00003850385	76441842	76442069

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 89.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.8765 / max 74.8760, expressed in 971 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79168	2.2400	765
79171	0.5660	294
79167	0.3984	222
79169	0.2246	125
79170	0.1794	100
79173	0.1328	65
79172	0.1137	50
79175	0.0214	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	89.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.49	gold quality
apex of heart	UBERON:0002098	83.07	gold quality
mucosa of transverse colon	UBERON:0004991	82.35	gold quality
bone marrow cell	CL:0002092	80.09	gold quality
ventricular zone	UBERON:0003053	79.03	gold quality
muscle tissue	UBERON:0002385	78.67	gold quality
body of pancreas	UBERON:0001150	78.62	gold quality
right adrenal gland cortex	UBERON:0035827	78.46	gold quality
esophagus mucosa	UBERON:0002469	78.30	gold quality
nucleus accumbens	UBERON:0001882	78.11	gold quality
fundus of stomach	UBERON:0001160	78.10	gold quality
skeletal muscle tissue	UBERON:0001134	77.98	gold quality
mucosa of stomach	UBERON:0001199	77.98	gold quality
putamen	UBERON:0001874	77.69	gold quality
right uterine tube	UBERON:0001302	77.67	gold quality
skin of leg	UBERON:0001511	77.36	gold quality
zone of skin	UBERON:0000014	77.15	gold quality
right adrenal gland	UBERON:0001233	76.88	gold quality
left adrenal gland cortex	UBERON:0035825	76.88	gold quality
blood	UBERON:0000178	76.74	gold quality
skin of abdomen	UBERON:0001416	76.68	gold quality
vagina	UBERON:0000996	76.67	gold quality
corpus callosum	UBERON:0002336	76.40	gold quality
left adrenal gland	UBERON:0001234	76.36	gold quality
thoracic mammary gland	UBERON:0005200	76.26	gold quality
pancreas	UBERON:0001264	76.21	gold quality
left ovary	UBERON:0002119	76.19	gold quality
ectocervix	UBERON:0012249	76.09	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8381	yes	2069.79
E-GEOD-36552	yes	411.72
E-ANND-3	no	2.35

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FIGLA, SOHLH1

Literature-anchored findings (GeneRIF, showing 26)

• Eggs expressing glycoprotein huZP3, derived from transgenic mice, bind murine but not human sperm, implying that huZP3 acquires the same O-glycans as native mZP3. (PMID:14673092)
• human and mouse ZP3 proteins are quite similar, and alternative explanations of taxon-specific sperm binding warrant exploration (PMID:15379548)
• Binding sites for recombinant zona pellucida C (ZPC) glycoprotein are located both at the N- and C-terminus of proacrosin (PMID:15950651)
• Exposure of sperm to ZP proteins promoted acrosomal exocytosis and changed motility patterns. (PMID:16407501)
• Peptides rhuZP3a22 approximately 176 and rhuZP3b177 approximately 348 have a role similar to human ZP3. The mechanism of the response to the peptides involves influx of calcium, the G protein pathway, and a T-type calcium channel. (PMID:17192598)
• ZP proteins were detected in both the oocyte and the granulosa cells as early as the primordial follicle stage in the human. The detection of ZP proteins in the quiescent primordial follicle suggests that these proteins have been present since oogenesis. (PMID:18033806)
• may have a role in the development of primordial follicle before zona pellucida formation (PMID:18502569)
• induces acrosome reactions which are protein kinase-C, protein tyrosine kinase, T-type Ca2+ channels, and extracellular Ca2+ dependent (PMID:18667750)
• a significant decrease in acrosomal exocytosis mediated by both recombinant human ZP3 (p<0.005) and ZP4 (p<0.005) was observed in presence of the immune sera (PMID:19004505)
• The functional activity of human ZP3 resides in its C-terminal domain. (PMID:19246320)
• observed sequence variations in exons of ZP3 gene in women with infertility of unknown origin who exhibit abnormal zona pellucida; sperm-ovum interactions appear relatively normal in these patients [CASE REPORTS] (PMID:22889493)
• Epididymal CRISP1 mediates sperm-zona pellucida binding through its interaction with ZP3. (PMID:24334245)
• The oocyte ZP3 expression was the main predictor of the fertilization capacity. (PMID:28204536)
• Mutations in ZP2 and ZP3 have dosage effects which can cause female infertility in humans. (PMID:28646452)
• Missense Mutation in ZP3 gene is associated with Empty Follicle Syndrome and Female Infertility. (PMID:28886344)
• The zona pellucida-3 (ZP3) protein plays a pivotal role in oocyte and gamete development. (PMID:30341457)
• Mutations in ZP1, ZP2, and ZP3 might affect the corresponding protein expression, secretion, and interaction, thus providing a mechanistic explanation for the phenotypes for female infertility. (PMID:30810869)
• Zona Pellucida Proteins, Fibrils, and Matrix. (PMID:32569527)
• Heterozygous mutations in ZP1 and ZP3 cause formation disorder of ZP and female infertility in human. (PMID:32573113)
• A novel mutation in ZP3 causes empty follicle syndrome and abnormal zona pellucida formation. (PMID:33140178)
• A novel homozygous variant in ZP2 causes abnormal zona pellucida formation and female infertility. (PMID:33604805)
• Novel expression of zona pellucida 3 protein in normal testis; potential functional implications. (PMID:34736966)
• A novel gene mutation in ZP3 loop region identified in patients with empty follicle syndrome. (PMID:34816529)
• Novel mutations in ZP2 and ZP3 cause female infertility in three patients. (PMID:35366744)
• Novel mutations in TUBB8 and ZP3 cause human oocyte maturation arrest and female infertility. (PMID:36335766)
• Novel variants in ZP1, ZP2 and ZP3 associated with empty follicle syndrome and abnormal zona pellucida. (PMID:36931917)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	zp3e	ENSDARG00000016908
danio_rerio	zp3b	ENSDARG00000039828
danio_rerio	zp3a.1	ENSDARG00000042129
danio_rerio	zp3a.2	ENSDARG00000042130
danio_rerio	zp3.2	ENSDARG00000090768
danio_rerio	zp3	ENSDARG00000114958
danio_rerio	zp3.2	ENSDARG00000115457
mus_musculus	Zp3	ENSMUSG00000004948
rattus_norvegicus	Zp3	ENSRNOG00000001434

Paralogs (1): POMZP3 (ENSG00000146707)

Protein

Protein identifiers

Zona pellucida sperm-binding protein 3 — P21754 (reviewed: P21754)

Alternative names: Sperm receptor, ZP3A/ZP3B, Zona pellucida glycoprotein 3, Zona pellucida protein C

All UniProt accessions (3): P21754, E9PFI9, H0Y3M4

UniProt curated annotations — full annotation on UniProt →

Function. Component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy. The zona pellucida is composed of 3 to 4 glycoproteins, ZP1, ZP2, ZP3, and ZP4. ZP3 is essential for sperm binding and zona matrix formation.

Subunit / interactions. Polymers of ZP2 and ZP3 organized into long filaments cross-linked by ZP1 homodimers. Interacts with ZP1 and ZP2.

Subcellular location. Zona pellucida Cell membrane.

Tissue specificity. Expressed in oocytes (at protein level).

Post-translational modifications. Proteolytically cleaved before the transmembrane segment to yield the secreted ectodomain incorporated in the zona pellucida. N-glycosylated. O-glycosylated; removal of O-linked glycans may play an important role in the post-fertilization block to polyspermy.

Disease relevance. Oocyte/zygote/embryo maturation arrest 3 (OZEMA3) [MIM:617712] An autosomal dominant infertility disorder characterized by abnormal oocytes that lack the zona pellucida, and oocytes degeneration. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The ZP domain is involved in the polymerization of the ZP proteins to form the zona pellucida.

Miscellaneous. Found in a second polymorphic locus which, due to an extra G residue in exon 8, has the potential to encode a truncated protein of 372 amino acids.

Similarity. Belongs to the ZP domain family. ZPC subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P21754-1	ZP3A	yes
P21754-2	ZP3B
P21754-3	3

RefSeq proteins (2): NP_001103824, NP_009086 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001507	ZP_dom	Domain
IPR017977	ZP_dom_CS	Conserved_site
IPR042235	ZP-C_dom	Homologous_superfamily
IPR048290	ZP_chr	Domain
IPR055355	ZP-C	Domain
IPR055356	ZP-N	Domain

Pfam: PF00100, PF23344

UniProt features (28 total): glycosylation site 6, disulfide bond 4, sequence variant 4, splice variant 3, chain 2, topological domain 2, signal peptide 1, sequence conflict 1, propeptide 1, transmembrane region 1, domain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21754-F1	77.32	0.52

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): 23

Disulfide bonds (4): 46–140, 78–99, 217–282, 239–300

Glycosylation sites (6): 125, 147, 156, 162, 163, 272

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2534343	Interaction With Cumulus Cells And The Zona Pellucida

MSigDB gene sets: 234 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_SINGLE_FERTILIZATION, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_DEPENDENT_EXOCYTOSIS, GOBP_INFLAMMATORY_RESPONSE, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_GROWTH, GOBP_OOGENESIS

GO Biological Process (21): positive regulation of type IV hypersensitivity (GO:0001809), blastocyst formation (GO:0001825), humoral immune response mediated by circulating immunoglobulin (GO:0002455), positive regulation of leukocyte migration (GO:0002687), positive regulation of humoral immune response (GO:0002922), binding of sperm to zona pellucida (GO:0007339), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-4 production (GO:0032753), egg coat formation (GO:0035803), positive regulation of T cell proliferation (GO:0042102), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), oocyte development (GO:0048599), positive regulation of inflammatory response (GO:0050729), positive regulation of acrosome reaction (GO:2000344), negative regulation of binding of sperm to zona pellucida (GO:2000360), positive regulation of acrosomal vesicle exocytosis (GO:2000368), positive regulation of ovarian follicle development (GO:2000386), positive regulation of antral ovarian follicle growth (GO:2000388), signal transduction (GO:0007165), single fertilization (GO:0007338)

GO Molecular Function (7): extracellular matrix structural constituent (GO:0005201), carbohydrate binding (GO:0030246), acrosin binding (GO:0032190), structural constituent of egg coat (GO:0035804), identical protein binding (GO:0042802), receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), extracellular matrix (GO:0031012), egg coat (GO:0035805), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Fertilization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of reproductive process	3
humoral immune response	2
positive regulation of cytokine production	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
binding	2
cellular anatomical structure	2
type IV hypersensitivity	1
regulation of type IV hypersensitivity	1
positive regulation of T cell mediated immunity	1
positive regulation of hypersensitivity	1
blastocyst development	1
anatomical structure formation involved in morphogenesis	1
immunoglobulin mediated immune response	1
positive regulation of immune system process	1
regulation of leukocyte migration	1
positive regulation of cell migration	1
leukocyte migration	1
regulation of humoral immune response	1
positive regulation of immune response	1
sperm-egg recognition	1
type II interferon production	1
regulation of type II interferon production	1
interleukin-4 production	1
regulation of interleukin-4 production	1
cellular process involved in reproduction in multicellular organism	1
oogenesis	1
T cell proliferation	1
regulation of T cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of T cell activation	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
germ cell development	1
oocyte differentiation	1
inflammatory response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
acrosome reaction	1

Protein interactions and networks

STRING

758 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZP3	ZP1	P60852	999
ZP3	ZP4	Q12836	999
ZP3	ZP2	Q05996	990
ZP3	PKDREJ	Q9NTG1	939
ZP3	PLAC1	Q9HBJ0	885
ZP3	GDF9	O60383	789
ZP3	SNU13	P55769	763
ZP3	ZAN	Q9Y493	759
ZP3	IZUMO1	Q8IYV9	754
ZP3	NOBOX	O60393	743
ZP3	FIGLA	Q6QHK4	734
ZP3	DAZL	Q92904	660
ZP3	BMP15	O95972	657
ZP3	CACNA1G	O43497	642
ZP3	ASTL	Q6HA08	632

IntAct

31 interactions, top by confidence:

A	B	Type	Score
ZP3	ZP3	psi-mi:“MI:0407”(direct interaction)	0.600
ZP3	VDAC2	psi-mi:“MI:0915”(physical association)	0.520
ZP3	UBAP2L	psi-mi:“MI:0915”(physical association)	0.490
ZP3	SPACA3	psi-mi:“MI:0915”(physical association)	0.490
ZP3	PCDH17	psi-mi:“MI:0915”(physical association)	0.490
ZP3	MICALL1	psi-mi:“MI:0915”(physical association)	0.490
ZP3	ACR	psi-mi:“MI:0407”(direct interaction)	0.440
ZP3	ODF2	psi-mi:“MI:0915”(physical association)	0.400
ZP3	TPI1	psi-mi:“MI:0915”(physical association)	0.400
ZP3	GSTM3	psi-mi:“MI:0915”(physical association)	0.400
ZP3	GAPDHS	psi-mi:“MI:0915”(physical association)	0.400
ZP3	GPX4	psi-mi:“MI:0915”(physical association)	0.400
ZP3	PKM	psi-mi:“MI:0915”(physical association)	0.400
ZP3	ENO1	psi-mi:“MI:0915”(physical association)	0.400
ZP1	ZP3	psi-mi:“MI:0914”(association)	0.350
ZP2	ZP3	psi-mi:“MI:0914”(association)	0.350
ZP3	ZP1	psi-mi:“MI:0914”(association)	0.350
ZP3	SERPINB8	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): ZP3 (Affinity Capture-RNA), ZP3 (Affinity Capture-RNA), ZP3 (Two-hybrid), ZP3 (Two-hybrid), FAM63A (Affinity Capture-MS), GET4 (Affinity Capture-MS), SERPINB8 (Affinity Capture-MS), ZP3 (Positive Genetic), ZP3 (Affinity Capture-RNA), UBAP2L (Two-hybrid), MRPS16 (Two-hybrid), SPACA3 (Two-hybrid), OR2L13 (Two-hybrid), PCDH17 (Two-hybrid), MICALL1 (Two-hybrid)

ESM2 similar proteins: G7PWZ3, I6M4H4, O08852, O54766, O77726, O95428, P08751, P10761, P17813, P20239, P21754, P23491, P35054, P37176, P42098, P42099, P43021, P47983, P47984, P48829, P48830, P48831, P48832, P48833, P48834, P53785, P53786, P60852, P79762, P97708, Q00193, Q05996, Q07104, Q07287, Q12836, Q3HRV3, Q3S2X5, Q5DID0, Q5DID3, Q62005

Diamond homologs: G5E8D7, P21754, P53785, Q925U0, P10761, P23491, P42098, P48830, P48831, P48832, P48833, P53786, P79762, P97708, Q6PJE2, Q60997, Q8CIZ5, Q95218, A8CG34, P52591, Q8K3Z9, Q96HA1, Q96KW2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SOHLH1	“up-regulates quantity by expression”	ZP3	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 16 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.

GO biological processes:

GO term	Partners	Fold	FDR
binding of sperm to zona pellucida	5	131.7×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	78
Likely benign	13
Benign	10

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1285239	NM_001110354.2(ZP3):c.499GAG[1] (p.Glu168del)	Pathogenic
1711657	NM_001110354.2(ZP3):c.831+1G>C	Pathogenic
437933	NM_001110354.2(ZP3):c.400G>A (p.Ala134Thr)	Pathogenic
689403	NM_001110354.2(ZP3):c.763C>G (p.Arg255Gly)	Pathogenic
1333775	NM_001110354.2(ZP3):c.157dup (p.Val53fs)	Likely pathogenic

SpliceAI

1836 predictions. Top by Δscore:

Variant	Effect	Δscore
7:76397833:C:CA	acceptor_loss	1.0000
7:76397834:T:A	acceptor_loss	1.0000
7:76398714:A:AC	donor_gain	1.0000
7:76398715:C:CC	donor_gain	1.0000
7:76398715:CGT:C	donor_gain	1.0000
7:76398715:CGTA:C	donor_gain	1.0000
7:76398716:GTA:G	donor_loss	1.0000
7:76398717:TA:T	donor_loss	1.0000
7:76398718:A:AC	donor_gain	1.0000
7:76398719:C:CT	donor_gain	1.0000
7:76398719:CT:C	donor_gain	1.0000
7:76398719:CTT:C	donor_gain	1.0000
7:76398719:CTTT:C	donor_gain	1.0000
7:76398795:ATTC:A	acceptor_loss	1.0000
7:76398796:TT:T	acceptor_gain	1.0000
7:76398797:TCT:T	acceptor_loss	1.0000
7:76398798:C:CC	acceptor_gain	1.0000
7:76398799:T:C	acceptor_loss	1.0000
7:76409409:CATA:C	donor_loss	1.0000
7:76409410:ATAC:A	donor_loss	1.0000
7:76409411:TA:T	donor_loss	1.0000
7:76409413:C:CG	donor_loss	1.0000
7:76425273:GCAG:G	donor_gain	1.0000
7:76425274:CAGGT:C	donor_loss	1.0000
7:76425276:GGT:G	donor_loss	1.0000
7:76425277:G:GG	donor_gain	1.0000
7:76425277:GT:G	donor_loss	1.0000
7:76425278:T:A	donor_loss	1.0000
7:76429510:TCCA:T	acceptor_loss	1.0000
7:76429512:CAGG:C	acceptor_loss	1.0000

AlphaMissense

2790 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:76440312:G:C	K298N	0.997
7:76440312:G:T	K298N	0.997
7:76434076:T:G	F251C	0.996
7:76434039:T:A	C239S	0.995
7:76434040:G:C	C239S	0.995
7:76429620:T:A	C140S	0.994
7:76429621:G:C	C140S	0.994
7:76434112:T:C	F263S	0.994
7:76440263:G:A	C282Y	0.994
7:76440264:C:G	C282W	0.994
7:76440316:T:A	C300S	0.994
7:76440317:G:C	C300S	0.994
7:76433583:T:A	C217S	0.993
7:76433584:G:C	C217S	0.993
7:76440262:T:A	C282S	0.993
7:76440262:T:C	C282R	0.993
7:76440263:G:C	C282S	0.993
7:76440478:G:C	W309C	0.993
7:76440478:G:T	W309C	0.993
7:76434075:T:C	F251L	0.992
7:76434077:C:A	F251L	0.992
7:76434077:C:G	F251L	0.992
7:76434133:T:G	F270C	0.992
7:76440269:T:C	L284P	0.992
7:76433584:G:A	C217Y	0.991
7:76434039:T:C	C239R	0.991
7:76433585:C:G	C217W	0.990
7:76434076:T:C	F251S	0.989
7:76434126:T:C	F268L	0.989
7:76434128:C:A	F268L	0.989

dbSNP variants (sampled 300 via entrez): RS1000029426 (7:76414463 C>G), RS1000104374 (7:76427838 G>A), RS1000116853 (7:76414070 C>G,T), RS1000193036 (7:76420027 C>G), RS1000303488 (7:76425748 T>C), RS1000484199 (7:76414057 C>G,T), RS1000490195 (7:76430454 G>A), RS1000614217 (7:76433577 G>A), RS1000614248 (7:76397660 G>A), RS1000643648 (7:76433797 T>C,G), RS1000716146 (7:76429025 C>T), RS1000827265 (7:76409872 T>A), RS1000895507 (7:76414414 G>A,T), RS1001020356 (7:76436577 A>G,T), RS1001060809 (7:76401868 T>C)

Disease associations

OMIM: gene MIM:182889 | disease phenotypes: MIM:617712

GenCC curated gene-disease

Disease	Classification	Inheritance
oocyte maturation defect 3	Strong	Autosomal dominant
female infertility due to zona pellucida defect	Supportive	Autosomal dominant
inherited oocyte maturation defect	Limited	Autosomal recessive

Mondo (3): oocyte maturation defect 3 (MONDO:0021574), inherited oocyte maturation defect (MONDO:0014769), female infertility due to zona pellucida defect (MONDO:0014342)

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0008222	Female infertility
HP:0011462	Young adult onset

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002778_4	Parkinson disease and lewy body pathology	7.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation, increases expression	3
Smoke	increases abundance, decreases expression	2
Tretinoin	decreases expression	2
aristolochic acid I	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
ICG 001	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, increases expression	1
jinfukang	increases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Azacitidine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Hydrogen Peroxide	affects expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Mustard Gas	increases expression	1
Ozone	increases expression	1
Rotenone	increases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_K172	HuZP3-CHOLec3.2.8.1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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