OVOL2

Summary

OVOL2 (ovo like zinc finger 2, HGNC:15804) is a protein-coding gene on chromosome 20p11.23, encoding Transcription factor Ovo-like 2 (Q9BRP0). Zinc-finger transcription repressor factor.

This gene encodes a member of the evolutionarily conserved ovo-like protein family. Mammalian members of this family contain a single zinc finger domain composed of a tetrad of C2H2 zinc fingers with variable N- and C-terminal extensions that contain intrinsically disordered domains. Members of this family are involved in epithelial development and differentiation. Knockout of this gene in mouse results in early embryonic lethality with phenotypes that include neurectoderm expansion, impaired vascularization, and heart anomalies. In humans, allelic variants of this gene have been associated with posterior polymorphous corneal dystrophy.

Source: NCBI Gene 58495 — RefSeq curated summary.

At a glance

• Gene–disease (curated): posterior polymorphous corneal dystrophy 1 (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 66 total — 4 pathogenic
• Phenotypes (HPO): 27
• Transcription factor: yes — 10 downstream targets (CollecTRI)
• MANE Select transcript: NM_021220

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15804
Approved symbol	OVOL2
Name	ovo like zinc finger 2
Location	20p11.23
Locus type	gene with protein product
Status	Approved
Aliases	bA504H3.3, HOVO2, CHED
Ensembl gene	ENSG00000125850
Ensembl biotype	protein_coding
OMIM	616441
Entrez	58495

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000278780, ENST00000462208, ENST00000483661, ENST00000486776, ENST00000494030

RefSeq mRNA: 3 — MANE Select: NM_021220 NM_001303461, NM_001303462, NM_021220

CCDS: CCDS13132

Canonical transcript exons

ENST00000278780 — 4 exons

Exon	Start	End
ENSE00001474882	18057535	18057916
ENSE00001905769	18024163	18024952
ENSE00003511115	18041534	18041723
ENSE00003615362	18056657	18056877

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 93.77.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3287 / max 32.0182, expressed in 405 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186535	0.6997	329
186534	0.2521	181
186533	0.1950	111
186536	0.1521	94
186537	0.0297	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	93.77	gold quality
mucosa of transverse colon	UBERON:0004991	88.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.86	gold quality
nasal cavity epithelium	UBERON:0005384	82.87	gold quality
epithelium of bronchus	UBERON:0002031	82.30	gold quality
bronchial epithelial cell	CL:0002328	82.24	gold quality
minor salivary gland	UBERON:0001830	82.07	gold quality
mucosa of sigmoid colon	UBERON:0004993	81.89	gold quality
colonic mucosa	UBERON:0000317	81.62	gold quality
bronchus	UBERON:0002185	81.54	gold quality
saliva-secreting gland	UBERON:0001044	81.00	gold quality
ileal mucosa	UBERON:0000331	80.75	gold quality
lower esophagus mucosa	UBERON:0035834	80.66	gold quality
skin of leg	UBERON:0001511	80.60	gold quality
skin of abdomen	UBERON:0001416	80.48	gold quality
mouth mucosa	UBERON:0003729	79.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.77	gold quality
nasal cavity mucosa	UBERON:0001826	79.77	gold quality
cervix squamous epithelium	UBERON:0006922	79.55	gold quality
palpebral conjunctiva	UBERON:0001812	79.36	gold quality
esophagus mucosa	UBERON:0002469	79.30	gold quality
rectum	UBERON:0001052	78.96	gold quality
zone of skin	UBERON:0000014	78.78	gold quality
right uterine tube	UBERON:0001302	78.55	gold quality
parotid gland	UBERON:0001831	78.46	gold quality
body of pancreas	UBERON:0001150	78.13	gold quality
jejunal mucosa	UBERON:0000399	77.32	gold quality
left lobe of thyroid gland	UBERON:0001120	77.31	gold quality
duodenum	UBERON:0002114	76.63	gold quality
right lobe of thyroid gland	UBERON:0001119	76.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.43

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

10 targets.

Target	Regulation
CDH2	Repression
H1-6
SMAD4	Repression
SMAD7	Activation
SNAI2	Repression
TWIST1	Repression
TWIST2	Repression
VIM	Repression
ZEB1	Repression
ZEB2	Repression

JASPAR motifs

Motif	Name	Family
MA1545.1	OVOL2	More than 3 adjacent zinc fingers
MA1545.2	OVOL2	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:24735879

Upstream regulators (CollecTRI, top): OVOL1

miRNA regulators (miRDB)

46 targeting OVOL2, 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-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7157-5P	99.66	69.33	1829

Literature-anchored findings (GeneRIF, showing 27)

• congenital hereditary endothelial dystrophy 1 (CHED1) and CHED2 loci on chromosome 20 and the collagen, type VIII, alpha-2 (COL8A2) gene were excluded by linkage and haplotype analyses. (PMID:12654361)
• We report the absence of a presumed pathogenic coding region mutation in the common PPCD1 support interval. (PMID:19574904)
• Ovol2 directly represses two critical downstream targets, c-Myc and Notch1, thereby suppressing keratinocyte transient proliferation and terminal differentiation, respectively (PMID:19700410)
• Molecular phylogeny of OVOL1, OVOL2 and OVOL3 genes illustrates a conserved C2H2 zinc finger domain coupled by hypervariable unstructured regions in humans and other species (PMID:22737237)
• OVOL2 is a colorectal tumor suppressor that blocks WNT signaling by facilitating the recruitment of histone deacetylase 1 to the TCF4-beta-catenin complex. (PMID:26619963)
• data demonstrate that all four mutated OVOL2 promoters exhibited more transcriptional activity than the corresponding wild-type promoter (PMID:26749309)
• that the OVOL1-OVOL2 axis may actively contribute to cell differentiation and proliferation in the hair bulb (PMID:26873447)
• OVOL2 maintains the transcriptional program of human corneal epithelium cells. (PMID:27134177)
• hOvol2 expression was restricted to the XY body of spermatocytes at the pachytene stage. This study demonstrates that hOvol2 is expressed in germ cells and may be involved in spermatogenesis. (PMID:27136193)
• Ovol2 can suppress migration and invasion ability of A549 cells, and prevent EMT by inhibition of Twist1 transcription directly. (PMID:27884772)
• the OVOL2 promoter variant c.-307T>C was herein identified in the original family that established the posterior polymorphous corneal dystrophy 1 locus. (PMID:28046031)
• Taken together, this study suggests that the OVOL1-OVOL2 axis is a key modulator of c-Myc expression in the shift from in situ epidermal malignancy (Bowen’s disease) to invasive squamous cell carcinoma. (PMID:28339425)
• OVOL2 antagonizes TGF-beta signaling to regulate epithelial to mesenchymal transition during mammary tumor metastasis. (PMID:28455959)
• OVOL2 only exhibits modest effect on epithelial-mesenchymal transition but has a strong impact on both metastasis and tumorigenesis. (PMID:29721073)
• The function of OVOL2 as a tumor suppressor in vivo is highly regulated by PARylation. (PMID:30542118)
• OVOL2 induces mesenchymal-to-epithelial transition in fibroblasts and enhances cell-state reprogramming towards epithelial lineages. (PMID:31019211)
• These findings suggest that alterations in the ZEB1-OVOL2-GRHL2 axis (caused by posterior polymorphous corneal dystrophy-associated mutations) lead to changes in corneal endothelial cell state and molecular pathways, including the aberrant activation of the Wnt signaling pathway. (PMID:31233731)
• TRPV1 is a potential therapeutic target in hepatocellular carcinoma and exerts effects on cellular plasticity with modulation of Ovol2, Zeb1 and Sox10. (PMID:31401394)
• Dysregulation of the Pdx1/Ovol2/Zeb2 axis in dedifferentiated beta-cells triggers the induction of genes associated with epithelial-mesenchymal transition in diabetes. (PMID:33989778)
• OVOL2 inhibits macrophage M2 polarization by regulating IL-10 transcription, and thus inhibits the tumor metastasis by modulating the tumor microenvironment. (PMID:34033850)
• OVOL2 attenuates the expression of MAP3K8 to suppress epithelial mesenchymal transition in colorectal cancer. (PMID:34098198)
• c.-61G>A in OVOL2 is a Pathogenic 5’ Untranslated Region Variant Causing Posterior Polymorphous Corneal Dystrophy 1. (PMID:34469340)
• Altered Epithelial-mesenchymal Plasticity as a Result of Ovol2 Deletion Minimally Impacts the Self-renewal of Adult Mammary Basal Epithelial Cells. (PMID:34984648)
• OVOL2 impairs RHO GTPase signaling to restrain mitosis and aggressiveness of Anaplastic Thyroid Cancer. (PMID:35337349)
• An NF-kappaB/OVOL2 circuit regulates glucose import and cell survival in non-small cell lung cancer. (PMID:35346238)
• Transcriptional Repression of Aerobic Glycolysis by OVOL2 in Breast Cancer. (PMID:35896951)
• Ovol2 promoter mutations in mice and human illuminate species-specific phenotypic divergence. (PMID:37971355)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:171929	ENSDARG00000100197
mus_musculus	Ovol2	ENSMUSG00000037279
rattus_norvegicus	Ovol2	ENSRNOG00000006850
drosophila_melanogaster	hb	FBGN0001180
drosophila_melanogaster	CG12391	FBGN0033581
caenorhabditis_elegans		WBGENE00001824
caenorhabditis_elegans		WBGENE00012385

Paralogs (29): ZNF446 (ENSG00000083838), REST (ENSG00000084093), ZNF174 (ENSG00000103343), OVOL3 (ENSG00000105261), PLAGL1 (ENSG00000118495), ZSCAN18 (ENSG00000121413), ZNF576 (ENSG00000124444), PLAGL2 (ENSG00000126003), ZSCAN5A (ENSG00000131848), ZSCAN29 (ENSG00000140265), ZSCAN32 (ENSG00000140987), ZSCAN1 (ENSG00000152467), ZNF18 (ENSG00000154957), ZKSCAN2 (ENSG00000155592), ZNF496 (ENSG00000162714), ZNF202 (ENSG00000166261), ZNF641 (ENSG00000167528), ZNF444 (ENSG00000167685), SCAND1 (ENSG00000171222), ZNF274 (ENSG00000171606), ZNF131 (ENSG00000172262), OVOL1 (ENSG00000172818), ZNF518A (ENSG00000177853), ZNF518B (ENSG00000178163), PLAG1 (ENSG00000181690), ZSCAN5B (ENSG00000197213), ZNF770 (ENSG00000198146), PEG3 (ENSG00000198300), ZSCAN5C (ENSG00000204532)

Protein

Protein identifiers

Transcription factor Ovo-like 2 — Q9BRP0 (reviewed: Q9BRP0)

Alternative names: Zinc finger protein 339

All UniProt accessions (1): Q9BRP0

UniProt curated annotations — full annotation on UniProt →

Function. Zinc-finger transcription repressor factor. Plays a critical role in maintaining the identity of epithelial lineages by suppressing epithelial-to mesenchymal transition (EMT) mainly through the repression of ZEB1, an EMT inducer. Positively regulates neuronal differentiation. Suppresses cell cycling and terminal differentiation of keratinocytes by directly repressing MYC and NOTCH1. Important for the correct development of primordial germ cells in embryos. Plays dual functions in thermogenesis and adipogenesis to maintain energy balance. Essential for brown/beige adipose tissue-mediated thermogenesis, is necessary for the development of brown adipocytes. In white adipose tissues, limits adipogenesis by blocking CEBPA binding to its transcriptional targets and inhibiting its transcription factor activity.

Subunit / interactions. Interacts (via zinc-finger domains) with CEBPA (via bZIP domain); the interaction inhibits the transcription factor activity of CEBPA and is required to repress adipogenesis.

Subcellular location. Nucleus.

Tissue specificity. Expressed in testis, ovary, heart and skeletal muscle. Expressed in the cornea, but absent from the corneal endothelium.

Disease relevance. Corneal dystrophy, posterior polymorphous, 1 (PPCD1) [MIM:122000] A rare corneal disorder characterized by small aggregates of apparent vesicles bordered by a gray haze at the level of Descemet membrane, an altered corneal endothelial cell structure, and an unusual proliferation of endothelial cells. Symptoms can range from very aggressive to asymptomatic and non-progressive, even within the same family. The disease is caused by variants affecting the gene represented in this entry. Disease-causing mutations in the OVOL2 promoter alter promoter activity, dysregulate OVOL2 expression, and probably induce OVOL2 ectopic expression in the corneal endothelium.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BRP0-1	1	yes
Q9BRP0-2	2

RefSeq proteins (1): NP_067043* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR027756	Ovo-like	Family
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF13894, PF13912

UniProt features (13 total): zinc finger region 4, compositionally biased region 4, chain 1, modified residue 1, splice variant 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BRP0-F1	61.52	0.00

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): 269

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 338 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, RNGTGGGC_UNKNOWN, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, E2F_Q4_01, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, WWTAAGGC_UNKNOWN, GOBP_HEART_TRABECULA_MORPHOGENESIS, GOBP_POSITIVE_REGULATION_OF_KERATINOCYTE_DIFFERENTIATION, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS

GO Biological Process (37): angiogenesis (GO:0001525), neural crest cell migration (GO:0001755), neural fold formation (GO:0001842), heart looping (GO:0001947), regulation of transcription by RNA polymerase II (GO:0006357), cell population proliferation (GO:0008283), epidermal cell differentiation (GO:0009913), dorsal/ventral pattern formation (GO:0009953), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), negative regulation of epithelial to mesenchymal transition (GO:0010719), regulation of keratinocyte proliferation (GO:0010837), obsolete negative regulation of transcription by competitive promoter binding (GO:0010944), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), negative regulation of keratinocyte differentiation (GO:0045617), positive regulation of keratinocyte differentiation (GO:0045618), negative regulation of Notch signaling pathway (GO:0045746), embryonic digestive tract morphogenesis (GO:0048557), regulation of cell cycle (GO:0051726), endocardium formation (GO:0060214), heart trabecula formation (GO:0060347), negative regulation of SMAD protein signal transduction (GO:0060392), labyrinthine layer blood vessel development (GO:0060716), negative regulation of white fat cell proliferation (GO:0070351), negative regulation of stem cell proliferation (GO:2000647), negative regulation of transcription by RNA polymerase II (GO:0000122), heart development (GO:0007507), negative regulation of cell population proliferation (GO:0008285), epidermis development (GO:0008544), negative regulation of signal transduction (GO:0009968), negative regulation of cell differentiation (GO:0045596), regulation of keratinocyte differentiation (GO:0045616), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of multicellular organismal process (GO:0051241), white fat cell proliferation (GO:0070343), positive regulation of cold-induced thermogenesis (GO:0120162)

GO Molecular Function (12): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), chromatin binding (GO:0003682), transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
anatomical structure formation involved in morphogenesis	3
gene expression	2
regulation of gene expression	2
negative regulation of multicellular organismal process	2
keratinocyte differentiation	2
regulation of keratinocyte differentiation	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
binding	2
blood vessel morphogenesis	1
neural crest cell development	1
mesenchymal cell migration	1
primary neural tube formation	1
morphogenesis of embryonic epithelium	1
morphogenesis of an epithelial fold	1
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
cellular process	1
epidermis development	1
epithelial cell differentiation	1
regionalization	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
negative regulation of cell differentiation	1
keratinocyte proliferation	1
regulation of epithelial cell proliferation	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of epidermal cell differentiation	1
positive regulation of epidermal cell differentiation	1
positive regulation of multicellular organismal process	1
Notch signaling pathway	1
regulation of Notch signaling pathway	1
negative regulation of signal transduction	1
digestive tract morphogenesis	1

Protein interactions and networks

STRING

711 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OVOL2	GRHL2	Q6ISB3	735
OVOL2	ZEB1	P37275	516
OVOL2	ESRP1	Q6NXG1	496
OVOL2	SNAI1	O95863	484
OVOL2	SNAI2	O43623	471
OVOL2	DZANK1	Q9NVP4	466
OVOL2	GRHL1	Q9NZI5	465
OVOL2	CDH1	P12830	448
OVOL2	TWIST1	Q15672	421
OVOL2	GRHL3	Q8TE85	407
OVOL2	ELF5	Q9UKW6	400
OVOL2	VIM	P08670	399
OVOL2	MRPL24	Q96A35	389
OVOL2	RBBP9	O75884	378
OVOL2	RBFOX1	Q9NWB1	376

IntAct

6 interactions, top by confidence:

A	B	Type	Score
ZNF526	OVOL2	psi-mi:“MI:0915”(physical association)	0.560
OVOL2	TNPO2	psi-mi:“MI:0914”(association)	0.350
OVOL2	ZNF526	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (143): OVOL2 (Affinity Capture-RNA), OVOL2 (Affinity Capture-MS), PARP1 (Affinity Capture-MS), PARP1 (Affinity Capture-Western), PARP1 (Reconstituted Complex), HDAC1 (Affinity Capture-Western), ZNF526 (Two-hybrid), LRP6 (Affinity Capture-MS), LRP5 (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS), TNPO2 (Affinity Capture-MS), HECTD3 (Affinity Capture-MS), KLHL36 (Affinity Capture-MS), RCOR1 (Affinity Capture-MS), RIC8B (Affinity Capture-MS)

ESM2 similar proteins: A1L2U9, A2APF3, A2BID7, A2VDT4, B1WAZ8, B1WBU4, G5E869, O08961, O14753, O43298, Q05516, Q0IH98, Q0VCJ6, Q13422, Q2I689, Q2M1K9, Q3U288, Q58NQ5, Q5NBY9, Q5TC79, Q5U2T6, Q6DJT9, Q6NS86, Q6ZPY5, Q80TS5, Q86UZ6, Q8BHZ4, Q8C208, Q8CCH7, Q8CIV7, Q8K0L9, Q8N1W2, Q8N895, Q8NCN2, Q8WW38, Q90W33, Q92610, Q96BR9, Q9BRP0, Q9BYN7

Diamond homologs: A2VDT4, D3YYM0, G5EDU6, O00110, O14753, P51521, Q8CIV7, Q9BRP0, Q9WTJ2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MDM2	“down-regulates quantity by destabilization”	OVOL2	ubiquitination

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	41
Likely benign	8
Benign	7

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
224837	NM_001303461.1(OVOL2):c.-297+895_-297+916dup	Pathogenic
224838	NM_001303461.1(OVOL2):c.-297+886T>C	Pathogenic
224839	NM_001303461.1(OVOL2):c.-297+949T>C	Pathogenic
224840	NM_021220.4(OVOL2):c.-274T>G	Pathogenic

SpliceAI

1987 predictions. Top by Δscore:

Variant	Effect	Δscore
20:17957033:CTCAG:C	acceptor_gain	1.0000
20:17969116:T:G	donor_gain	1.0000
20:17970371:G:GG	donor_gain	1.0000
20:17975904:G:GG	donor_gain	1.0000
20:17988294:TTCAG:T	donor_loss	1.0000
20:17988295:TCAG:T	donor_loss	1.0000
20:17988296:CAG:C	donor_loss	1.0000
20:17988297:AGGTC:A	donor_loss	1.0000
20:17988298:GG:G	donor_loss	1.0000
20:17988299:GTCA:G	donor_loss	1.0000
20:17988300:T:G	donor_loss	1.0000
20:17988304:GACAC:G	donor_gain	1.0000
20:18024949:ATGC:A	acceptor_gain	1.0000
20:18024950:TGC:T	acceptor_gain	1.0000
20:18024951:GC:G	acceptor_gain	1.0000
20:18024952:CC:C	acceptor_gain	1.0000
20:18024953:C:CC	acceptor_gain	1.0000
20:18024953:C:CG	acceptor_loss	1.0000
20:18024961:A:AC	acceptor_gain	1.0000
20:18041530:TCA:T	donor_loss	1.0000
20:18041532:A:AC	donor_gain	1.0000
20:18041532:A:AG	donor_loss	1.0000
20:18041533:C:CC	donor_gain	1.0000
20:18041720:TGAA:T	acceptor_gain	1.0000
20:18041724:C:CC	acceptor_gain	1.0000
20:17957034:TCAG:T	acceptor_gain	0.9900
20:17957035:CAG:C	acceptor_gain	0.9900
20:17957035:CAGC:C	acceptor_gain	0.9900
20:17957036:AG:A	acceptor_gain	0.9900
20:17957036:AGCT:A	acceptor_loss	0.9900

AlphaMissense

1818 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:18024912:G:C	F184L	1.000
20:18024912:G:T	F184L	1.000
20:18024913:A:G	F184S	1.000
20:18024914:A:G	F184L	1.000
20:18024935:A:G	C177R	1.000
20:18041538:G:C	H169Q	1.000
20:18041538:G:T	H169Q	1.000
20:18041545:C:G	R167P	1.000
20:18041560:A:G	L162P	1.000
20:18041577:G:C	F156L	1.000
20:18041577:G:T	F156L	1.000
20:18041578:A:G	F156S	1.000
20:18041579:A:G	F156L	1.000
20:18041600:A:G	C149R	1.000
20:18041661:G:C	F128L	1.000
20:18041661:G:T	F128L	1.000
20:18041663:A:G	F128L	1.000
20:18024818:A:G	C216R	0.999
20:18024883:A:G	L194P	0.999
20:18024885:G:C	H193Q	0.999
20:18024885:G:T	H193Q	0.999
20:18024886:T:G	H193P	0.999
20:18024887:G:C	H193D	0.999
20:18024887:G:T	H193N	0.999
20:18024895:A:G	L190P	0.999
20:18024914:A:T	F184I	0.999
20:18024918:T:A	K182N	0.999
20:18024918:T:G	K182N	0.999
20:18024924:G:C	C180W	0.999
20:18024925:C:G	C180S	0.999

dbSNP variants (sampled 300 via entrez): RS1000054647 (20:18040161 C>A), RS1000157845 (20:18027160 A>G), RS1000199117 (20:18056226 C>A,G,T), RS1000288942 (20:18046444 A>G), RS1000335967 (20:18054195 T>C), RS1000553019 (20:18025706 G>A), RS1000718325 (20:18030733 T>C), RS1000765452 (20:18036441 G>T), RS1000955260 (20:18036091 C>A,T), RS1000978648 (20:18030361 G>A), RS1001009286 (20:18025862 T>C), RS1001053776 (20:18031646 A>G,T), RS1001062273 (20:18041399 G>A,C), RS1001366675 (20:18058435 T>A), RS1001387236 (20:18028102 G>A,C)

Disease associations

OMIM: gene MIM:616441 | disease phenotypes: MIM:122000

GenCC curated gene-disease

Disease	Classification	Inheritance
posterior polymorphous corneal dystrophy 1	Definitive	Autosomal dominant
posterior polymorphous corneal dystrophy	Supportive	Autosomal dominant
congenital hereditary endothelial dystrophy type I	Supportive	Autosomal dominant

Mondo (3): posterior polymorphous corneal dystrophy 1 (MONDO:0007378), posterior polymorphous corneal dystrophy (MONDO:0020364), congenital hereditary endothelial dystrophy type I (MONDO:0020365)

Orphanet (1): Posterior polymorphous corneal dystrophy (Orphanet:98973)

HPO phenotypes

27 total (27 of 27 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000483	Astigmatism
HP:0000501	Glaucoma
HP:0000533	Chorioretinal atrophy
HP:0000565	Esotropia
HP:0000585	Band keratopathy
HP:0000613	Photophobia
HP:0000622	Blurred vision
HP:0000632	Lacrimation abnormality
HP:0000646	Amblyopia
HP:0001089	Iris atrophy
HP:0007663	Reduced visual acuity
HP:0007906	Ocular hypertension
HP:0007915	Polymorphous posterior corneal dystrophy
HP:0007957	Corneal opacity
HP:0009918	Ectopia pupillae
HP:0009926	Epiphora
HP:0011483	Anterior synechiae of the anterior chamber
HP:0011488	Abnormal corneal endothelium morphology
HP:0011490	Abnormal Descemet membrane morphology
HP:0011491	Reduced number of corneal endothelial cells
HP:0012040	Corneal stromal edema
HP:0025358	Uveal ectropion
HP:0031159	Thinning of Descemet membrane
HP:0032122	Very low visual acuity
HP:0100692	Increased corneal curvature
HP:0200026	Ocular pain

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST010105_143	Nicotine dependence symptom count	2.000000e-07
GCST010105_203	Nicotine dependence symptom count	2.000000e-07
GCST010204_24	Low density lipoprotein cholesterol levels	8.000000e-41
GCST90002390_691	Mean corpuscular hemoglobin	4.000000e-13
GCST90002392_97	Mean corpuscular volume	5.000000e-13
GCST90002403_312	Red blood cell count	7.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009262	nicotine dependence symptom count
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	4
mercuric bromide	increases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	increases abundance, increases expression, decreases expression	2
methylmercuric chloride	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
trichostatin A	increases expression	1
butyraldehyde	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Panobinostat	affects cotreatment, increases expression	1
Amphotericin B	increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Carbamazepine	affects expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	decreases expression	1
Hydrogen Peroxide	affects expression	1
Nickel	decreases expression	1
Silicon Dioxide	decreases expression	1
Urethane	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5B7	SEES3-1V human OVOL2, clone1	Embryonic stem cell	Male
CVCL_A5B8	SEES3-1V human OVOL2, clone2	Embryonic stem cell	Male
CVCL_A5B9	SEES3-1V human OVOL2, clone3	Embryonic stem cell	Male
CVCL_E0YG	Ubigene MCF-7 OVOL2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00800111	Not specified	COMPLETED	Study of Endothelial Keratoplasty Outcomes
NCT02020044	Not specified	UNKNOWN	Outcome After Descemet Membrane Endothelial Keratoplasty (DMEK) and Ultra-thin Descemet Stripping Automated Endothelial Keratoplasty (DSAEK)
NCT04387331	Not specified	UNKNOWN	The Postoperative Head Position as a Predictor of the Surgical Outcome After DMEK