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OOEP (Oocyte expressed protein)

Written2019-03Luigi Cristiano
Aesthetic and medical biotechnologies research unit, Prestige, Terranuova Bracciolini, Italy;;

Abstract Oocyte expressed protein, alias OOEP, is a component of the subcortical maternal complex (SCMC) that play its roles in oocytes and in early stages of embryogenesis. In this review it is done an insight on its DNA, its RNA, its protein encoded and on the diseases where OOEP is involved.

Keywords OOEP; Oocyte expressed protein; subcortical maternal complex, SCMC, embryogenesis, zygote

(Note : for Links provided by Atlas : click)


Alias (NCBI)C6orf156
chromosome 6 open reading frame 156
Factor Located in Oocytes Permitting Embryonic Development
KH homology domain containing 2
KH homology domain-containing protein 2
KH Homology Domain Containing 2
oocyte and embryo protein 19
oocyte expressed protein homolog (dog)
oocyte- and embryo-specific protein 19
oocyte-expressed protein homolog
HGNC Alias symbEm:AC019205.2
HGNC Alias nameKH homology domain containing 2
HGNC Previous nameC6orf156
HGNC Previous namechromosome 6 open reading frame 156
 oocyte expressed protein homolog (dog)
LocusID (NCBI) 441161
Atlas_Id 71121
Location 6q13  [Link to chromosome band 6q13]
Location_base_pair Starts at 73368557 and ends at 73369792 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping OOEP.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)


  Figure. 1. OOEP gene, transcript and splicing variants/isoforms. The figure shows the locus on chromosome 6 of the OOEP gene, its transcript and its alternative splicing/isoforms (blue). The primary transcript is OOEP-201 mRNA (orange), but also EEF1G-202/203 variants seem be able to codify a protein (reworked from;;
Description OOEP, alias oocyte expressed protein, is a protein coding gene that starts at 73,368,555 nt and ends at 73,369,792nnt from qter and with a length of 1238 bp. The current reference sequence is NC_000006.12 and contain 3 exons. It is proximal to KHDC3L (KH domain containing 3 like, subcortical maternal complex member) gene and to RPL39P3 (ribosomal protein L39 pseudogene 3) gene. Around the genomic locus of OOEP take place different promoter or enhancer transcriptional elements. Two strong elements are closer to the sequence of OOEP gene and are located at +0.3 kb and at -27.3 kb respectively.
Transcription OOEP transcript is 689 bp long with a reference sequence reported in GeneBank as NM_001080507. It lacks the 5' UTR, the CDS is extended from 1 to 450 nt and the 3' UTR is extended in the remaining part of the sequence, i.e. from 451 to 689 nt.
Splice variants for OOEP was observed: the main reference variant is OOEP (OOEP-201) and the others are OOEP-202 and OOEP-203 (Figure.1). OOEP-202, 1007 nt long, is formed by a fragment of exon 3, by the entire exon 2, it lacks the first exon and gains a forth distant element. OOEP-203, 964 nt long, lacks exons 3 and 1, maintains the entire exon2 and gains another distant element. All three transcript variants encode a protein.
Pseudogene For OOEP are known some pseudogenes that are classified as processed pseudogenes and are listed in Table 1.
GeneGene  nameRefSeqLocusLocationStartEndLenght (nt)
AL499605.1-201  OOEP pseudogene  ENST00000604628.1  1p21.1  Chrom. 1106544342  106544744  403
AL355333.1OOEP pseudogeneENSG00000270234  10p14Chrom. 10  87240108724288279

Table.1 OOEP pseudogenes (reworked from


  Figure.2 OOEP protein structure. (1) Primary structure of OOEP with emphasis on its main domain; (2) protein-protein interactions in the SCMC complex (reworked from Babbere et al., 2016).
Description The canonical sequence for OOEP protein (RefSeq NP_001073976) counts 149 amino acids and has a molecular weight of 17.17 kDa and a theoretical pI of 6.59. Contains a KH-domain, a typical domain of the type I superfamily of RNA binding proteins (Herr et al., 2008), that could mediate RNA transcript regulation during the oogenesis and early embryogenesis stages.
There are known other two isoforms produced by alternative splicing: the isoform OOEP-202 (UniRef, F2Z364) is formed by 94 residues and has a molecular weight of 10.72 kDa, while the isoform OOEP-203 (UniRef, C9J915) counts 67 amino acids and has 7.70 kDa of molecular weight.
Expression OOEP, as the others factors of the subcortical maternal complex (SCMC), is uniquely expressed in mammalian oocytes and in early embryo (Bebbere et al., 2016). However, some authors found mouse OOEP transcripts also in ovary and thymus, although the protein could not be detected. This may suggest that the transcript remains untranslated (Herr et al., 2008) and perhaps plays a regulatory function. The human OOEP mRNA was found in pituitary gland (Herr et al., 2008; Carninci and Hayashizaki, 1999), placenta ( and testis, where it was overexpressed (; tissues/HS/UniProt/A6NGQ2). It was also found in traces in ovary, endometrium, prostate, salivary gland, adrenal, appendix, brain, digestive system and related organs (esophagus, stomach, duodenum, small intestine, colon, gall bladder, liver, pancreas), lung, fat cells, heart, spleen, thyroid and urinary bladder (from https://www.ncbi.
Localisation OOEP is located in the cytoplasm.
Function OOEP is a component of the subcortical maternal complex (SCMC) that includes at least other three proteins, i.e. KHDC3L (also known as KH domain containing protein 3, FILIA), NLRP5 (also called Maternal Antigen That Embryo Requires, MATER) and TLE6 (also known as Transducin-Like Enhancer of Split 6). These proteins are expressed by maternal effect genes (MEGs) exclusively in oocytes and early embryos and are physically bound together in the SCMC complex. Also only a mutation on one of them, such as TLE6, induces instability of the complex and may be a cause of human female infertility and earliest human embryonic lethality (Bebbere et al., 2016; Alazami et al., 2015; Zhu et al., 2015; Bebbere et al., 2014).
OOEP plays an essential role for zygote progression beyond the first embryonic cell divisions (Bebbere et al., 2014) and it is hypotized that it could play a role in the formation/stabilization of the oocyte cytoskeleton, called oocyte cytoplasmic lattices (CPLs) and also it could be involved in the organization and regulation of the translational machinery through the interaction between SCMC complex with other protein and/or protein complexes (Bebbere et al., 2016; Tashiro et al., 2010). In addition, OOEP could be involved in RNA degradation during oocyte maturation and in the early stages of embryogenesis (Wang et al., 2012) and it could be directly or indirectly involved in the binding of the mRNAs and in their correct subcellular localization (Bebbere et al., 2016). In mouse oocytes was found that OOEP may participate in the regulation of genome stability (He et al., 2018), but it is not confirmed in humans yet.
Homology OOEP is highly and abundant conserved in many species and its homology between the species is reported in Table.2
OrganismSpeciesSymbol DNA Similarity (%)  PROT Similarity (%)
Chimpanzee  P.troglodytes  OOEP 99.3 99.3
Mouse M.musculusOOEP68.254.6

Table.2 OOEP homology (reworked from


Note The genomic alterations observed include the formation of novel fusion genes as EEF1G/OOEP (acute lymphoblastic leukemia/lymphoblastic lymphoma), EXOC2/OOEP (bladder transitional cell carcinoma), FAM19A2/OOEP (breast adenocarcinoma), KHDC1/OOEP, OOEP/ EIF3A, RERE/OOEP (prostate adenocarcinoma) and SENP6/OOEP (prostate adenocarcinoma) ( Bands/6q13.html), however there are no experimental data yet to understand the impact on cellular behaviour and so the implications in cancer of these fusion genes.

Implicated in

Note OOEP is a maternal-effect gene that is expressed in zygote and in early stages of embryo development. It is linked with female infertility, however there is some evidence of its involvement in cancers. We review the diseases in which OOEP gene showed overexpression, upregulation or aberrant fusion with other genes. Anyhow some authors found a downregulation of OOEP in ovarian cancer patient samples (Veskimäe et al., 2018), in colon cancer (Penrose et al., 2019) and in prostate cancer cells (Lu et al., 2015).
Disease Acute lymphoblastic leukemia/lymphoblastic lymphoma (Atak et al, 2013)
Hybrid/Mutated Gene T-cell acute lymphoblastic leukemia (T-ALL) affects about 15% of pediatric patients and 25% of adult patients of total ALL cases. It is an agressive tumor characterized by the accumulation of multiple genomic mutations and chromosomal aberrations, such as frequently chromosomal translocations, that bring to the formation of many in-frame fusion genes encoding the respective chimeric and oncogenic proteins (Atak et al., 2013). Among all these chromosomal aberrations it was found also the fusion gene 5' EEF1G / 3' OOEP deriving by the genomic translocation and fusion of a part of OOEP gene, situated on chromosome 6, with a portion of EEF1G gene, located on chromosome 11. This leads to the know but not still well-characterized translocation t(6;11)(q13;q12) EEF1G/OOEP.
Entity Human female infertility/ early embryo lethality
Disease Aberrant expression of SCMC members, such as OOEP, could compromise the fertility in women but also could be linked to abnormalities in preimplantation embryo development and in early lethality of the human embryos and so cover a significant role both in female inability to get pregnant and in failure of the development of implanted embryo after in vitro reproductive assistance procedures (Bebbere et al., 2016; Alazami et al., 2015; Zhu et al., 2015; Zhang et al., 2008).
To effort these considerations, an experiment in mouse demonstrated that a lack of OOEP gene (OOEP -/- knockout mice) causes complete infertility and disorganization/abnormalities in oocyte cytoplasmic lattices (CPLs). However, Ooep-null mice females grew to adulthood and showed no apparent abnormalities except the infertility (Tashiro et al., 2010).
Entity Osteosarcoma
Note Some authors found OOEP gene upregulated in osteosarcoma cells (Li et al., 2017).
Entity Small cell lung carcinoma
Note The expression of OOEP is increased in small cell lung carcinoma (Jiang et al., 2016).
Entity Testis cancer
Note Some databases reported that the expression of OOEP is increased in testis cancer (; HS/UniProt/A6NGQ2) but is not clear if also protein can be displayed.
Entity Thyroid cancer
Note One database reported high levels for the presence of OOEP protein in thyroid cancer although its expression level in this cancer type was reported to be lower ( ENSG00000203907-OOEP/pathology).


TLE6 mutation causes the earliest known human embryonic lethality
Alazami AM, Awad SM, Coskun S, Al-Hassan S, Hijazi H, Abdulwahab FM, Poizat C, Alkuraya FS
Genome Biol 2015 Nov 5;16:240
PMID 26537248
Comprehensive analysis of transcriptome variation uncovers known and novel driver events in T-cell acute lymphoblastic leukemia
Atak ZK, Gianfelici V, Hulselmans G, De Keersmaecker K, Devasia AG, Geerdens E, Mentens N, Chiaretti S, Durinck K, Uyttebroeck A, Vandenberghe P, Wlodarska I, Cloos J, Foà R, Speleman F, Cools J, Aerts S
PLoS Genet 2013;9(12):e1003997
PMID 24367274
Expression of maternally derived KHDC3, NLRP5, OOEP and TLE6 is associated with oocyte developmental competence in the ovine species
Bebbere D, Ariu F, Bogliolo L, Masala L, Murrone O, Fattorini M, Falchi L, Ledda S
BMC Dev Biol 2014 Nov 25;14:40
PMID 25420964
The subcortical maternal complex: multiple functions for one biological structure? J Assist Reprod Genet
Bebbere D, Masala L, Albertini DF, Ledda S
2016 Nov;33(11):1431-1438 Epub 2016 Aug 15
PMID 27525657
High-efficiency full-length cDNA cloning
Carninci P, Hayashizaki Y
Methods Enzymol 1999;303:19-44
PMID 10349636
Maternal gene Ooep may participate in homologous recombination-mediated DNA double-strand break repair in mouse oocytes
He DJ, Wang L, Zhang ZB, Guo K, Li JZ, He XC, Cui QH, Zheng P
Zool Res 2018 Nov 18;39(6):387-395
PMID 29955025
Distribution of RNA binding protein MOEP19 in the oocyte cortex and early embryo indicates pre-patterning related to blastomere polarity and trophectoderm specification
Herr JC, Chertihin O, Digilio L, Jha KN, Vemuganti S, Flickinger CJ
Dev Biol 2008 Feb 15;314(2):300-16
PMID 18191828
Genomic Landscape Survey Identifies SRSF1 as a Key Oncodriver in Small Cell Lung Cancer
Jiang L, Huang J, Higgs BW, Hu Z, Xiao Z, Yao X, Conley S, Zhong H, Liu Z, Brohawn P, Shen D, Wu S, Ge X, Jiang Y, Zhao Y, Lou Y, Morehouse C, Zhu W, Sebastian Y, Czapiga M, Oganesyan V, Fu H, Niu Y, Zhang W, Streicher K, Tice D, Zhao H, Zhu M, Xu L, Herbst R, Su X, Gu Y, Li S, Huang L, Gu J, Han B, Jallal B, Shen H, Yao Y
PLoS Genet 2016 Apr 19;12(4):e1005895
PMID 27093186
Transcriptomic analyses reveal the underlying pro-malignant functions of PTHR1 for osteosarcoma via activation of Wnt and angiogenesis pathways
Li S, Dong Y, Wang K, Wang Z, Zhang X
J Orthop Surg Res 2017 Nov 9;12(1):168
PMID 29121993
Messenger RNA profile analysis deciphers new Esrrb responsive genes in prostate cancer cells
Lu Y, Li J, Cheng J, Lubahn DB
BMC Mol Biol 2015 Dec 1;16:21
PMID 26627478
Loss of Forkhead Box O3 Facilitates Inflammatory Colon Cancer: Transcriptome Profiling of the Immune Landscape and Novel Targets
Penrose HM, Cable C, Heller S, Ungerleider N, Nakhoul H, Baddoo M, Hartono AB, Lee SB, Burow ME, Flemington EF, Crawford SE, Savkovic SD
Cell Mol Gastroenterol Hepatol 2019;7(2):391-408
PMID 30718226
Maternal-effect gene Ces5/Ooep/Moep19/Floped is essential for oocyte cytoplasmic lattice formation and embryonic development at the maternal-zygotic stage transition
Tashiro F, Kanai-Azuma M, Miyazaki S, Kato M, Tanaka T, Toyoda S, Yamato E, Kawakami H, Miyazaki T, Miyazaki J
Genes Cells 2010 Aug;15(8):813-28
PMID 20590823
Expression Analysis of Platinum Sensitive and Resistant Epithelial Ovarian Cancer Patient Samples Reveals New Candidates for Targeted Therapies
Veskimäe K, Scaravilli M, Niininen W, Karvonen H, Jaatinen S, Nykter M, Visakorpi T, Mäenpæ J, Ungureanu D, Staff S
Transl Oncol 2018 Oct;11(5):1160-1170
PMID 30056367
The N-terminus of FILIA forms an atypical KH domain with a unique extension involved in interaction with RNA
Wang J, Xu M, Zhu K, Li L, Liu X
PLoS One 2012;7(1):e30209
PMID 22276159
Expression analysis of the NLRP gene family suggests a role in human preimplantation development
Zhang P, Dixon M, Zucchelli M, Hambiliki F, Levkov L, Hovatta O, Kere J
PLoS One 2008 Jul 23;3(7):e2755
PMID 18648497
Identification of a human subcortical maternal complex
Zhu K, Yan L, Zhang X, Lu X, Wang T, Yan J, Liu X, Qiao J, Li L
Mol Hum Reprod 2015 Apr;21(4):320-9
PMID 25542835


This paper should be referenced as such :
Luigi Cristiano
OOEP (Oocyte expressed protein)
Atlas Genet Cytogenet Oncol Haematol. 2020;24(3):112-116.
Free journal version : [ pdf ]   [ DOI ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(6;11)(q13;q12) EEF1G::OOEP

External links


HGNC (Hugo)OOEP   21382
Entrez_Gene (NCBI)OOEP    oocyte expressed protein
AliasesC6orf156; FLOPED; HOEP19; KHDC2
GeneCards (Weizmann)OOEP
Ensembl hg19 (Hinxton)ENSG00000203907 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000203907 [Gene_View]  ENSG00000203907 [Sequence]  chr6:73368557-73369792 [Contig_View]  OOEP [Vega]
ICGC DataPortalENSG00000203907
Genatlas (Paris)OOEP
SOURCE (Princeton)OOEP
Genetics Home Reference (NIH)OOEP
Genomic and cartography
GoldenPath hg38 (UCSC)OOEP  -     chr6:73368557-73369792 -  6q13   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)OOEP  -     6q13   [Description]    (hg19-Feb_2009)
GoldenPathOOEP - 6q13 [CytoView hg19]  OOEP - 6q13 [CytoView hg38]
Genome Data Viewer NCBIOOEP [Mapview hg19]  
Gene and transcription
Genbank (Entrez)BC024931 BX093821 EU290647
RefSeq transcript (Entrez)NM_001080507
Consensus coding sequences : CCDS (NCBI)OOEP
Gene ExpressionOOEP [ NCBI-GEO ]   OOEP [ EBI - ARRAY_EXPRESS ]   OOEP [ SEEK ]   OOEP [ MEM ]
Gene Expression Viewer (FireBrowse)OOEP [ Firebrowse - Broad ]
GenevisibleExpression of OOEP in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)441161
GTEX Portal (Tissue expression)OOEP
Human Protein AtlasENSG00000203907-OOEP [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtA6NGQ2   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtA6NGQ2  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProA6NGQ2
Domains : Interpro (EBI)KH_dom_type_1_sf    MOEP19_KH-like    OOEP   
Domain families : Pfam (Sanger)MOEP19 (PF16005)   
Domain families : Pfam (NCBI)pfam16005   
Conserved Domain (NCBI)OOEP
AlphaFold pdb e-kbA6NGQ2   
Human Protein Atlas [tissue]ENSG00000203907-OOEP [tissue]
Protein Interaction databases
IntAct (EBI)A6NGQ2
Ontologies - Pathways
Ontology : AmiGORNA binding  protein binding  nucleus  nucleus  cytoplasm  cell cortex  actin filament organization  biological_process  embryonic pattern specification  replication fork processing  regulation of protein localization  protein-containing complex  protein-containing complex  establishment or maintenance of apical/basal cell polarity  apical cortex  positive regulation of meiotic nuclear division  establishment of spindle localization  regulation of cell division  regulation of establishment of protein localization  subcortical maternal complex  positive regulation of double-strand break repair via homologous recombination  positive regulation of double-strand break repair  
Ontology : EGO-EBIRNA binding  protein binding  nucleus  nucleus  cytoplasm  cell cortex  actin filament organization  biological_process  embryonic pattern specification  replication fork processing  regulation of protein localization  protein-containing complex  protein-containing complex  establishment or maintenance of apical/basal cell polarity  apical cortex  positive regulation of meiotic nuclear division  establishment of spindle localization  regulation of cell division  regulation of establishment of protein localization  subcortical maternal complex  positive regulation of double-strand break repair via homologous recombination  positive regulation of double-strand break repair  
NDEx NetworkOOEP
Atlas of Cancer Signalling NetworkOOEP
Wikipedia pathwaysOOEP
Orthology - Evolution
GeneTree (enSembl)ENSG00000203907
Phylogenetic Trees/Animal Genes : TreeFamOOEP
Homologs : HomoloGeneOOEP
Homology/Alignments : Family Browser (UCSC)OOEP
Gene fusions - Rearrangements
Fusion : QuiverOOEP
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerOOEP [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)OOEP
Exome Variant ServerOOEP
GNOMAD BrowserENSG00000203907
Varsome BrowserOOEP
ACMGOOEP variants
Genomic Variants (DGV)OOEP [DGVbeta]
DECIPHEROOEP [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisOOEP 
ICGC Data PortalOOEP 
TCGA Data PortalOOEP 
Broad Tumor PortalOOEP
OASIS PortalOOEP [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICOOEP  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DOOEP
Mutations and Diseases : HGMDOOEP
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)OOEP
DoCM (Curated mutations)OOEP
CIViC (Clinical Interpretations of Variants in Cancer)OOEP
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry OOEP
NextProtA6NGQ2 [Medical]
Target ValidationOOEP
Huge Navigator OOEP [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDOOEP
Pharm GKB GenePA162398414
Clinical trialOOEP
DataMed IndexOOEP
PubMed8 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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