OOEP

Summary

OOEP (oocyte expressed protein, HGNC:21382) is a protein-coding gene on chromosome 6q13, encoding Oocyte-expressed protein homolog (A6NGQ2). Component of the subcortical maternal complex (SCMC), a multiprotein complex that plays a key role in early embryonic development.

Predicted to enable RNA binding activity. Predicted to be involved in several processes, including cytoskeleton organization; positive regulation of double-strand break repair via homologous recombination; and positive regulation of meiotic nuclear division. Predicted to act upstream of or within several processes, including embryo implantation; in utero embryonic development; and protein phosphorylation. Located in cytoplasm and nucleus. Part of subcortical maternal complex.

Source: NCBI Gene 441161 — RefSeq curated summary.

At a glance

• Gene–disease (curated): female infertility due to oocyte meiotic arrest (Moderate, GenCC)
• Clinical variants (ClinVar): 30 total
• MANE Select transcript: NM_001080507

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21382
Approved symbol	OOEP
Name	oocyte expressed protein
Location	6q13
Locus type	gene with protein product
Status	Approved
Aliases	Em:AC019205.2, KHDC2
Ensembl gene	ENSG00000203907
Ensembl biotype	protein_coding
OMIM	611689
Entrez	441161

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000370359, ENST00000370363, ENST00000441145

RefSeq mRNA: 2 — MANE Select: NM_001080507 NM_001080507, NM_001428256

CCDS: CCDS47451

Canonical transcript exons

ENST00000370359 — 3 exons

Exon	Start	End
ENSE00001452467	73369603	73369897
ENSE00001452472	73368555	73368863
ENSE00001547343	73369206	73369385

Expression profiles

Bgee: expression breadth ubiquitous, 127 present calls, max score 99.92.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8384 / max 42.9928, expressed in 277 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74364	0.5821	247
74363	0.1737	84
74362	0.0761	30
204059	0.0065	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.92	gold quality
secondary oocyte	CL:0000655	99.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.06	gold quality
sperm	CL:0000019	82.91	gold quality
left testis	UBERON:0004533	80.25	gold quality
right testis	UBERON:0004534	80.19	gold quality
testis	UBERON:0000473	79.78	gold quality
tibialis anterior	UBERON:0001385	71.20	silver quality
pancreatic ductal cell	CL:0002079	68.58	silver quality
epithelial cell of pancreas	CL:0000083	68.33	gold quality
mucosa of transverse colon	UBERON:0004991	66.11	gold quality
adult organism	UBERON:0007023	65.10	gold quality
placenta	UBERON:0001987	62.78	gold quality
cartilage tissue	UBERON:0002418	62.73	gold quality
esophagus squamous epithelium	UBERON:0006920	62.56	gold quality
ileal mucosa	UBERON:0000331	62.41	silver quality
amniotic fluid	UBERON:0000173	60.56	gold quality
deltoid	UBERON:0001476	58.07	gold quality
granulocyte	CL:0000094	57.46	gold quality
mucosa of paranasal sinus	UBERON:0005030	56.73	gold quality
myocardium	UBERON:0002349	56.11	gold quality
parotid gland	UBERON:0001831	55.80	gold quality
nasal cavity epithelium	UBERON:0005384	55.43	gold quality
endothelial cell	CL:0000115	55.39	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	53.72	gold quality
germinal epithelium of ovary	UBERON:0001304	53.65	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	1043.15
E-ANND-3	no	1.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting OOEP, 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-6867-5P	100.00	82.21	3464
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-374B-3P	98.63	68.24	1360
HSA-MIR-676-5P	98.49	68.87	1492
HSA-MIR-4450	98.26	68.35	725
HSA-MIR-595	98.25	67.44	699
HSA-MIR-503-5P	97.87	66.83	575

Literature-anchored findings (GeneRIF, showing 1)

• Mutations in OOEP and NLRP5 identified in infertile patients with early embryonic arrest. (PMID:35946397)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ooep	ENSMUSG00000032346
rattus_norvegicus	Ooep	ENSRNOG00000025957

Paralogs (1): KHDC3L (ENSG00000203908)

Protein

Protein identifiers

Oocyte-expressed protein homolog — A6NGQ2 (reviewed: A6NGQ2)

Alternative names: KH homology domain-containing protein 2, Oocyte- and embryo-specific protein 19

All UniProt accessions (3): A6NGQ2, C9J915, F2Z364

UniProt curated annotations — full annotation on UniProt →

Function. Component of the subcortical maternal complex (SCMC), a multiprotein complex that plays a key role in early embryonic development. The SCMC complex is a structural constituent of cytoplasmic lattices, which consist in fibrous structures found in the cytoplasm of oocytes and preimplantation embryos. They are required to store maternal proteins critical for embryonic development, such as proteins that control epigenetic reprogramming of the preimplantation embryo, and prevent their degradation or activation. As part of the OOEP-KHDC3 scaffold, recruits BLM and TRIM25 to DNA replication forks, thereby promoting the ubiquitination of BLM by TRIM25, enhancing BLM retainment at replication forks and therefore promoting stalled replication fork restart. Positively regulates the homologous recombination-mediated DNA double-strand break (DSB) repair pathway by regulating ATM activation and RAD51 recruitment to DSBs in oocytes. Thereby contributes to oocyte survival and the resumption and completion of meiosis.

Subunit / interactions. Component of the subcortical maternal complex (SCMC), at least composed of NLRP5, KHDC3L, OOEP, and TLE6 isoform 1. Within the complex, interacts with NLRP5, KHDC3L and TLE6 isoform 1. As part of the SCMC interacts with the SCMC-associated protein NLRP4F. The SCMC may facilitate translocation of its components between the nuclear and cytoplasmic compartments. Forms a scaffold complex with KHDC3L/FILIA, and interacts with BLM and TRIM25 at DNA replication forks.

Subcellular location. Cytoplasm. Nucleus.

Domain organisation. Contains an atypical KH domain with amino acid changes at critical sites, suggesting that it may not bind RNA.

Similarity. Belongs to the KHDC1 family.

RefSeq proteins (2): NP_001073976, NP_001415185 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031952	MOEP19_KH-like	Domain
IPR036612	KH_dom_type_1_sf	Homologous_superfamily
IPR051778	KHDC1	Family

Pfam: PF16005

UniProt features (18 total): strand 5, helix 4, sequence variant 4, chain 1, domain 1, turn 1, region of interest 1, mutagenesis site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8X7V	ELECTRON MICROSCOPY	3.01
8X7W	ELECTRON MICROSCOPY	3.36
9L4L	ELECTRON MICROSCOPY	3.4
9L4K	ELECTRON MICROSCOPY	3.41

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NGQ2-F1	83.08	0.62

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
109–116	impaired formation of the subcortical maternal complex (scmc).

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 106 (showing top): GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION, GOBP_SPINDLE_LOCALIZATION, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_MEIOTIC_CELL_CYCLE, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_POSITIVE_REGULATION_OF_MEIOTIC_CELL_CYCLE, GOBP_ORGANELLE_FISSION, GOBP_EMBRYONIC_PATTERN_SPECIFICATION

GO Biological Process (12): actin filament organization (GO:0007015), embryonic pattern specification (GO:0009880), replication fork processing (GO:0031297), regulation of protein localization (GO:0032880), establishment or maintenance of apical/basal cell polarity (GO:0035088), positive regulation of meiotic nuclear division (GO:0045836), establishment of spindle localization (GO:0051293), regulation of cell division (GO:0051302), regulation of establishment of protein localization (GO:0070201), protein storage (GO:0140089), positive regulation of double-strand break repair via homologous recombination (GO:1905168), positive regulation of double-strand break repair (GO:2000781)

GO Molecular Function (3): RNA binding (GO:0003723), structural constituent of cytoplasmic lattice (GO:0140094), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), cell cortex (GO:0005938), protein-containing complex (GO:0032991), subcortical maternal complex (GO:0106333), cytoplasmic lattice (GO:0140095)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
actin cytoskeleton organization	1
supramolecular fiber organization	1
pattern specification process	1
embryo development	1
DNA-templated DNA replication maintenance of fidelity	1
intracellular protein localization	1
regulation of localization	1
establishment or maintenance of bipolar cell polarity	1
regulation of meiotic nuclear division	1
positive regulation of meiotic cell cycle	1
positive regulation of nuclear division	1
positive regulation of cell cycle process	1
meiotic nuclear division	1
microtubule cytoskeleton organization	1
establishment of localization in cell	1
spindle localization	1
establishment of organelle localization	1
regulation of cellular process	1
cell division	1
regulation of protein localization	1
establishment of protein localization	1
nutrient storage	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
positive regulation of DNA recombination	1
positive regulation of double-strand break repair	1
double-strand break repair	1
positive regulation of DNA repair	1
regulation of double-strand break repair	1
nucleic acid binding	1
structural molecule activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
cell periphery	1
cellular_component	1
protein-containing complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

344 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OOEP	TLE6	Q9H808	999
OOEP	KHDC1	Q4VXA5	974
OOEP	PADI6	Q6TGC4	965
OOEP	NLRP5	P59047	949
OOEP	KHDC3L	Q587J8	830
OOEP	NLRP2	Q9NX02	779
OOEP	ZBED3	Q96IU2	735
OOEP	NLRP7	Q8WX94	629
OOEP	ZAR1	Q86SH2	609
OOEP	PRR23E	Q8N813	477
OOEP	DDX1	Q92499	473
OOEP	SEBOX	Q9HB31	459
OOEP	SMCO3	A2RU48	450
OOEP	DPPA3	Q6W0C5	447
OOEP	PATL2	C9JE40	430

IntAct

36 interactions, top by confidence:

A	B	Type	Score
ABI2	OOEP	psi-mi:“MI:0915”(physical association)	0.560
OOEP	SNRPB	psi-mi:“MI:0915”(physical association)	0.560
OOEP	LONRF1	psi-mi:“MI:0915”(physical association)	0.560
OOEP	KIF9	psi-mi:“MI:0915”(physical association)	0.560
OOEP	AIRIM	psi-mi:“MI:0915”(physical association)	0.560
OOEP	TCEANC	psi-mi:“MI:0915”(physical association)	0.560
OOEP	ALOX5	psi-mi:“MI:0915”(physical association)	0.560
OOEP	ABI2	psi-mi:“MI:0915”(physical association)	0.560
OOEP	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
OOEP	ENKD1	psi-mi:“MI:0915”(physical association)	0.560
OOEP	KHDC3L	psi-mi:“MI:0915”(physical association)	0.460
KHDC3L	OOEP	psi-mi:“MI:0915”(physical association)	0.460
KHDC3L	OOEP	psi-mi:“MI:0403”(colocalization)	0.460
NLRP5	OOEP	psi-mi:“MI:0915”(physical association)	0.400
OOEP	TLE6	psi-mi:“MI:0915”(physical association)	0.400
TLE6	OOEP	psi-mi:“MI:0915”(physical association)	0.400
OOEP	NLRP7	psi-mi:“MI:0915”(physical association)	0.400
SNRPB	OOEP	psi-mi:“MI:0915”(physical association)	0.000
LONRF1	OOEP	psi-mi:“MI:0915”(physical association)	0.000
TCEANC	OOEP	psi-mi:“MI:0915”(physical association)	0.000
ALOX5	OOEP	psi-mi:“MI:0915”(physical association)	0.000
NTAQ1	OOEP	psi-mi:“MI:0915”(physical association)	0.000
KIF9	OOEP	psi-mi:“MI:0915”(physical association)	0.000
AIRIM	OOEP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): OOEP (Two-hybrid), OOEP (Two-hybrid), OOEP (Two-hybrid), OOEP (Two-hybrid), OOEP (Two-hybrid), OOEP (Two-hybrid), OOEP (Two-hybrid), OOEP (Two-hybrid), OOEP (Two-hybrid), OOEP (Affinity Capture-MS), OOEP (Positive Genetic)

ESM2 similar proteins: A0JNQ6, A6NC42, A6NGQ2, A6NGR9, A6QP75, A7E3N7, A9X185, E1BDF2, E9PGG2, F6SZT2, P0C7A0, P85965, Q06VW1, Q0ZFW8, Q14DK4, Q3UK37, Q3UV16, Q3ZBN4, Q400G9, Q4VXA5, Q587J8, Q5JSQ8, Q60953, Q60I26, Q60I27, Q6NUI2, Q6ZUX3, Q810I0, Q8BH06, Q8C0R7, Q8IWB1, Q8IWY9, Q8IYX4, Q8K4C2, Q8N6L0, Q8N7F7, Q8NCV1, Q8TE82, Q91WA6, Q95JV3

Diamond homologs: A0JNQ6, A6NC42, A6NGQ2, A9X185, Q06VW1, Q0ZFW8, Q9CWE6, F6SZT2, P85965, Q587J8, Q9CQS7, D3ZVV1, Q9CWU5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

347 predictions. Top by Δscore:

Variant	Effect	Δscore
6:73369656:AGTT:A	donor_gain	0.9900
6:73369659:T:TA	donor_gain	0.9900
6:73369719:CGCAG:C	donor_gain	0.9900
6:73369257:TC:T	donor_gain	0.9800
6:73369382:GGGCC:G	acceptor_gain	0.9800
6:73369383:GGCCT:G	acceptor_gain	0.9800
6:73369384:GCCT:G	acceptor_gain	0.9800
6:73395104:G:GT	donor_gain	0.9800
6:73368864:C:CC	acceptor_gain	0.9700
6:73369174:T:TA	donor_gain	0.9700
6:73369382:GGGC:G	acceptor_loss	0.9700
6:73369383:GGCC:G	acceptor_loss	0.9700
6:73369596:CGCT:C	donor_loss	0.9700
6:73369597:GCTC:G	donor_loss	0.9700
6:73369598:CTCAC:C	donor_loss	0.9700
6:73369599:T:TA	donor_loss	0.9700
6:73369602:C:CG	donor_loss	0.9700
6:73369386:C:CC	acceptor_gain	0.9600
6:73369601:A:AC	donor_gain	0.9600
6:73369602:C:CC	donor_gain	0.9600
6:73369626:G:A	donor_gain	0.9600
6:73369673:C:CT	donor_gain	0.9600
6:73394992:G:GT	donor_gain	0.9600
6:73395050:G:GA	donor_gain	0.9600
6:73368859:CTCAG:C	acceptor_gain	0.9500
6:73368861:CAG:C	acceptor_gain	0.9500
6:73369595:TCGC:T	donor_loss	0.9500
6:73368940:T:TC	acceptor_gain	0.9300
6:73369385:CCT:C	acceptor_gain	0.9300
6:73369674:C:CT	donor_gain	0.9300

AlphaMissense

960 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:73369675:A:G	W40R	0.982
6:73369675:A:T	W40R	0.982
6:73369670:A:C	F41L	0.980
6:73369670:A:T	F41L	0.980
6:73369672:A:G	F41L	0.980
6:73369354:C:A	E74D	0.973
6:73369354:C:G	E74D	0.973
6:73369285:G:C	F97L	0.972
6:73369285:G:T	F97L	0.972
6:73369287:A:G	F97L	0.972
6:73369289:A:T	V96D	0.970
6:73369283:C:T	G98E	0.967
6:73369671:A:G	F41S	0.965
6:73369255:C:A	K107N	0.963
6:73369255:C:G	K107N	0.963
6:73369673:C:A	W40C	0.957
6:73369673:C:G	W40C	0.957
6:73369295:A:G	I94T	0.951
6:73369295:A:C	I94S	0.950
6:73369284:C:A	G98W	0.945
6:73369671:A:C	F41C	0.939
6:73369267:C:A	Q103H	0.931
6:73369267:C:G	Q103H	0.931
6:73369283:C:A	G98V	0.924
6:73369301:A:T	V92D	0.924
6:73369356:C:T	E74K	0.924
6:73369295:A:T	I94N	0.921
6:73369284:C:G	G98R	0.909
6:73369284:C:T	G98R	0.909
6:73369674:C:A	W40L	0.908

dbSNP variants (sampled 300 via entrez): RS1000338324 (6:73369520 GAA>G), RS1000853553 (6:73370582 C>G), RS1000941999 (6:73370608 G>A), RS1001305732 (6:73370271 C>T), RS1001310409 (6:73370906 T>G), RS1001345995 (6:73371129 G>A), RS1001967508 (6:73371616 G>A,C), RS1002299478 (6:73371421 G>A), RS1003818984 (6:73368683 A>C), RS1003849804 (6:73371557 T>C), RS1004191157 (6:73369049 C>A,G), RS1005497008 (6:73369939 G>A,T), RS1006089036 (6:73371472 G>C), RS1008098116 (6:73368610 T>C), RS1008463394 (6:73368953 A>C)

Disease associations

OMIM: gene MIM:611689 | disease phenotypes: MIM:615774

GenCC curated gene-disease

Disease	Classification	Inheritance
female infertility due to oocyte meiotic arrest	Moderate	Autosomal recessive

Mondo (2): inherited oocyte maturation defect (MONDO:0014769), female infertility due to oocyte meiotic arrest (MONDO:0044626)

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

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol S	increases methylation	1
Benzo(a)pyrene	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Testosterone	decreases expression	1
Permethrin	increases expression	1

Clinical trials (associated diseases)

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