ZEB1
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Also known as BZPZEBAREB6NIL-2-AZfhepZfhx1aFECD6
Summary
ZEB1 (zinc finger E-box binding homeobox 1, HGNC:11642) is a protein-coding gene on chromosome 10p11.22, encoding Zinc finger E-box-binding homeobox 1 (P37275). Acts as a transcriptional repressor. In precision oncology, ZEB1 Expression confers sensitivity to Salinomycin in Mantle Cell Lymphoma (CIViC Level D); 4 further curated variant–drug associations are listed below.
This gene encodes a zinc finger transcription factor. The encoded protein likely plays a role in transcriptional repression of interleukin 2. Mutations in this gene have been associated with posterior polymorphous corneal dystrophy-3 and late-onset Fuchs endothelial corneal dystrophy. Alternatively spliced transcript variants encoding different isoforms have been described.
Source: NCBI Gene 6935 — RefSeq curated summary.
At a glance
- Gene–disease (curated): posterior polymorphous corneal dystrophy 3 (Definitive, GenCC) — +4 more curated relationships
- GWAS associations: 5
- Clinical variants (ClinVar): 209 total — 21 pathogenic, 7 likely-pathogenic
- Phenotypes (HPO): 32
- Precision-oncology evidence (CIViC): 5 curated variant–drug associations
- Cancer driver (intOGen): activating (oncogene-like) across 6 cancer types
- Transcription factor: yes — 70 downstream targets (CollecTRI)
- MANE Select transcript:
NM_001174096
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:11642 |
| Approved symbol | ZEB1 |
| Name | zinc finger E-box binding homeobox 1 |
| Location | 10p11.22 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | BZP, ZEB, AREB6, NIL-2-A, Zfhep, Zfhx1a, FECD6 |
| Ensembl gene | ENSG00000148516 |
| Ensembl biotype | protein_coding |
| OMIM | 189909 |
| Entrez | 6935 |
Gene structure
Transcript identifiers
Ensembl transcripts: 25 — 9 protein_coding, 9 retained_intron, 6 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay
ENST00000320985, ENST00000424869, ENST00000437844, ENST00000446923, ENST00000488625, ENST00000493835, ENST00000542815, ENST00000542879, ENST00000557827, ENST00000558440, ENST00000558655, ENST00000558832, ENST00000558863, ENST00000559496, ENST00000559858, ENST00000560196, ENST00000560721, ENST00000560909, ENST00000561061, ENST00000561212, ENST00000561304, ENST00000606161, ENST00000606671, ENST00000860471, ENST00000860472
RefSeq mRNA: 41 — MANE Select: NM_001174096
NM_001128128, NM_001174093, NM_001174094, NM_001174095, NM_001174096, NM_001323638, NM_001323641, NM_001323642, NM_001323643, NM_001323644, NM_001323645, NM_001323646, NM_001323647, NM_001323648, NM_001323649, NM_001323650, NM_001323651, NM_001323652, NM_001323653, NM_001323654, NM_001323655, NM_001323656, NM_001323657, NM_001323658, NM_001323659, NM_001323660, NM_001323661, NM_001323662, NM_001323663, NM_001323664, NM_001323665, NM_001323666, NM_001323671, NM_001323672, NM_001323673, NM_001323674, NM_001323675, NM_001323676, NM_001323677, NM_001323678, NM_030751
CCDS: CCDS44370, CCDS53505, CCDS53506, CCDS53507, CCDS7169
Canonical transcript exons
ENST00000424869 — 9 exons
| Exon | Start | End |
|---|---|---|
| ENSE00003587924 | 31495776 | 31495838 |
| ENSE00003695302 | 31523933 | 31524113 |
| ENSE00003695612 | 31520126 | 31521936 |
| ENSE00003699576 | 31461037 | 31461237 |
| ENSE00003699919 | 31319216 | 31319292 |
| ENSE00003701577 | 31514603 | 31514708 |
| ENSE00003702391 | 31502348 | 31502509 |
| ENSE00003725201 | 31510673 | 31510875 |
| ENSE00003907264 | 31526672 | 31529804 |
Expression profiles
Bgee: expression breadth ubiquitous, 287 present calls, max score 99.15.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.8704 / max 1065.2756, expressed in 1518 samples.
FANTOM5 promoters (9 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 104601 | 23.4152 | 1444 |
| 104605 | 0.9899 | 310 |
| 104599 | 0.8649 | 380 |
| 104598 | 0.4393 | 179 |
| 104600 | 0.3406 | 180 |
| 104602 | 0.2829 | 163 |
| 104603 | 0.2582 | 116 |
| 104604 | 0.1661 | 67 |
| 104606 | 0.1132 | 48 |
Top tissues by expression
292 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| calcaneal tendon | UBERON:0003701 | 99.15 | gold quality |
| colonic epithelium | UBERON:0000397 | 98.41 | gold quality |
| tendon | UBERON:0000043 | 98.37 | gold quality |
| blood vessel layer | UBERON:0004797 | 98.24 | gold quality |
| decidua | UBERON:0002450 | 98.20 | gold quality |
| cranial nerve II | UBERON:0000941 | 98.17 | gold quality |
| gluteal muscle | UBERON:0002000 | 98.13 | gold quality |
| endothelial cell | CL:0000115 | 97.70 | gold quality |
| skeletal muscle tissue of rectus abdominis | UBERON:0004511 | 97.70 | gold quality |
| biceps brachii | UBERON:0001507 | 97.65 | gold quality |
| tendon of biceps brachii | UBERON:0008188 | 97.52 | gold quality |
| skeletal muscle tissue of biceps brachii | UBERON:0004502 | 97.46 | gold quality |
| cauda epididymis | UBERON:0004360 | 97.37 | gold quality |
| stromal cell of endometrium | CL:0002255 | 96.90 | gold quality |
| triceps brachii | UBERON:0001509 | 96.77 | gold quality |
| ganglionic eminence | UBERON:0004023 | 96.65 | gold quality |
| cartilage tissue | UBERON:0002418 | 96.60 | gold quality |
| heart right ventricle | UBERON:0002080 | 96.57 | gold quality |
| pericardium | UBERON:0002407 | 96.53 | gold quality |
| synovial joint | UBERON:0002217 | 96.16 | gold quality |
| diaphragm | UBERON:0001103 | 95.99 | gold quality |
| periodontal ligament | UBERON:0008266 | 95.73 | gold quality |
| parietal pleura | UBERON:0002400 | 95.58 | gold quality |
| pleura | UBERON:0000977 | 95.53 | gold quality |
| myometrium | UBERON:0001296 | 95.52 | gold quality |
| sural nerve | UBERON:0015488 | 95.49 | gold quality |
| visceral pleura | UBERON:0002401 | 95.21 | gold quality |
| saphenous vein | UBERON:0007318 | 95.20 | gold quality |
| seminal vesicle | UBERON:0000998 | 95.08 | gold quality |
| entorhinal cortex | UBERON:0002728 | 94.95 | gold quality |
Single-cell (SCXA)
Detected in 8 experiment(s), a significant marker in 7.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-HCAD-35 | yes | 65.86 |
| E-CURD-119 | yes | 41.25 |
| E-GEOD-135922 | yes | 35.32 |
| E-HCAD-25 | yes | 16.45 |
| E-GEOD-83139 | yes | 7.02 |
| E-ENAD-27 | yes | 6.13 |
| E-CURD-112 | no | 2.56 |
| E-ANND-3 | no | 0.00 |
Regulation
Is transcription factor: yes
Downstream targets (CollecTRI)
70 targets.
| Target | Regulation |
|---|---|
| ACTG2 | Unknown |
| ADAM2 | |
| AR | Unknown |
| ATP1A1 | Activation |
| BCL6 | Repression |
| BGLAP | Repression |
| BMI1 | Activation |
| CCN2 | |
| CCN6 | |
| CCNG2 | Activation |
| CD4 | Unknown |
| CDH1 | Activation |
| CDH13 | Unknown |
| CDH17 | |
| CDH2 | Activation |
| CDH5 | Repression |
| CDK2 | Activation |
| CDK4 | Activation |
| CDKN1A | Unknown |
| CDKN2A | |
| CDKN2B | Repression |
| COL1A1 | Repression |
| COL1A2 | Repression |
| COL2A1 | Unknown |
| COL4A3 | Unknown |
| CRYBB1 | |
| CTNNB1 | Repression |
| CXADR | Repression |
| EPCAM | Repression |
| ESR1 | Unknown |
JASPAR motifs
| Motif | Name | Family |
|---|---|---|
| MA0103.2 | ZEB1 | HD-ZF factors |
| MA0103.3 | ZEB1 | HD-ZF factors |
| MA0103.4 | ZEB1 | HD-ZF factors |
JASPAR matrix evidence (PMIDs): PMID:8065305
Upstream regulators (CollecTRI, top): CTNNB1, DAB2IP, E2F1, EP300, ERG, ESR1, ETS1, FLYWCH1, GATA3, GLI2, GRHL2, HOXA5, KAT2B, LBX1, LMO2, MITF, NEUROD2, NFKB, OVOL2, PCGF2, PGR, RELA, SALL4, SATB2, SIX1, SNAI1, TCF7L2, TWIST1, ZEB2
miRNA regulators (miRDB)
215 targeting ZEB1, 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-200B-3P | 100.00 | 73.31 | 2693 |
| HSA-MIR-200C-3P | 100.00 | 73.35 | 2685 |
| HSA-MIR-429 | 100.00 | 73.44 | 2698 |
| HSA-MIR-6867-5P | 100.00 | 82.21 | 3464 |
| HSA-MIR-3163 | 100.00 | 77.23 | 8605 |
| HSA-MIR-5692A | 100.00 | 74.40 | 6850 |
| HSA-MIR-450A-1-3P | 100.00 | 69.33 | 1837 |
| HSA-MIR-656-3P | 100.00 | 72.15 | 2788 |
| HSA-MIR-126-5P | 100.00 | 72.71 | 3180 |
| HSA-MIR-4533 | 100.00 | 69.48 | 2758 |
| HSA-MIR-340-5P | 100.00 | 72.50 | 4437 |
| HSA-MIR-3613-3P | 100.00 | 76.36 | 7965 |
| HSA-MIR-4262 | 100.00 | 73.26 | 3931 |
| HSA-MIR-3662 | 99.99 | 73.82 | 5684 |
| HSA-MIR-548C-3P | 99.99 | 74.01 | 7587 |
| HSA-MIR-150-5P | 99.99 | 66.69 | 1976 |
| HSA-MIR-4282 | 99.99 | 75.36 | 6408 |
| HSA-MIR-186-5P | 99.99 | 70.83 | 3707 |
| HSA-MIR-4803 | 99.98 | 71.99 | 3117 |
| HSA-MIR-548N | 99.98 | 71.94 | 4170 |
| HSA-MIR-548P | 99.98 | 72.25 | 3784 |
| HSA-MIR-499A-5P | 99.98 | 70.79 | 1323 |
| HSA-MIR-4789-5P | 99.98 | 70.76 | 2721 |
| HSA-MIR-5696 | 99.98 | 72.36 | 4487 |
| HSA-MIR-27A-3P | 99.98 | 72.13 | 2955 |
| HSA-MIR-27B-3P | 99.98 | 72.13 | 2955 |
| HSA-MIR-9985 | 99.98 | 72.11 | 2939 |
| HSA-MIR-3065-5P | 99.97 | 71.56 | 3281 |
| HSA-MIR-302C-5P | 99.97 | 72.56 | 3642 |
| HSA-MIR-1229-3P | 99.97 | 66.49 | 906 |
Literature-anchored findings (GeneRIF, showing 40)
- ZEB1 plays a role in repressing E-cadherin and MUC1 in epithelial cells [ZEB-1] (PMID:12161443)
- These data provide the first demonstration that Zfhep is post-translationally modified. (PMID:12163027)
- Data show that ZEB-1/deltaEF1 and ZEB-2/SIP1 are regulators of transforming growth factor beta/bone morphogenetic protein signaling, with opposing effects on this pathway. (PMID:12743038)
- while ZEB-1/deltaEF1 binds to p300 and promotes the formation of a p300-Smad transcriptional complex, ZEB-2/SIP1 acts as a repressor by recruiting CtBP (PMID:12743039)
- an activator of transcription whose action may be DNA-context and cell-type specific, but not species specific. (PMID:14965470)
- Data demonstrate that DNA methylation contributes to increased levels of p73 in Fanconi anemia cells by hampering the binding of the transcriptional repressor ZEB to an intronic regulatory region of the p73 gene. (PMID:16087177)
- In colon cancer parients, the correlation between the expression of SNAIL and the downregulation of E-cadherin (CDH1) is lost when ZEB1 is overexpressed (PMID:16203744)
- Levels of expression of CtBP and p300 are critical for the action of SNAIL and ZEB1, which have a pivotal role in levels of epithelial-mesenchymsal transitionin human colon carcinoma. (PMID:16804902)
- zinc-finger-enhancer protein 1 (ZEB1) is the crucial transcriptional repressor of BM components in CRCs. (PMID:16952552)
- The transcriptional repression of PKP3 by ZEB1 contributes to ZEB1-mediated disintegration of intercellular adhesion and epithelial to mesenchymal transition. (PMID:17391671)
- Four novel pathogenic mutations were identified in four families; two deletions, one nonsense, and one duplication within exon 7 in the ZEB1 gene at 10p11.2. Czech patients were genotyped for a founder haplotype and lack of 20p11.2 locus segregation. (PMID:17437275)
- Upregulation of ZEB1 is associated with colon and breast cancer progression (PMID:17486063)
- The Zfhx1a-1 gene is autoregulated in part by negative feedback on its own promoter which is, in turn, modified by the availability of the negative dominant isoform Zfhx1a-2. (PMID:17610840)
- TCF8 gene mutations are associated with Posterior polymorphous corneal dystrophy and abdominal hernia (PMID:17935237)
- Based on these observations we suggest that bHLH factors recruit NFI to enhance skeletal muscle Na(+) channel expression. (PMID:17936922)
- The identification of a novel missense mutation in only one of the patients implied that TCF8 does not play a significant role in the pathogenesis of FECD in this Chinese population. (PMID:18172091)
- ZEB1 is a crucial promoter of malignant tumor progression. (PMID:18199550)
- These results lead to a new hypothesis that Snail and ZEB1 are downstream of CCN6 and play a critical role in CCN6-mediated regulation of E-cadherin in breast cancer. (PMID:18321996)
- Data show that miR-200 and -205 microRNAs cooperatively regulate expression of the E-cadherin transcriptional repressors ZEB1 (also known as deltaEF1) and SIP1 (also known as ZEB2), factors previously implicated in EMT and tumour metastasis. (PMID:18376396)
- loss of expression of the miR-200 family members may play a critical role in the repression of E-cadherin by ZEB1 and ZEB2 during EMT, thereby enhancing migration and invasion during cancer progression. (PMID:18411277)
- Down-regulation of TCF8 expression in ATLL cells was associated with resistance to TGF-beta1, a well-known characteristic of ATLL cells, suggesting that escape from TGF-beta1-mediated growth inhibition is important in the pathogenesis of ATLL (PMID:18467597)
- These results indicate that ZEB1 triggers an microRNA-mediated feedforward loop that stabilizes the epithelial-mesenchymal transition and promotes invasion of cancer cells. (PMID:18483486)
- ZEB1 may be a biomarker of aggressive endometrial cancers at high risk of recurrence. (PMID:18487993)
- These data support the contention that high ZEB1 encourages gynecologic carcinoma progression. (PMID:18622689)
- A double-negative feedback loop controlling ZEB1-SIP1 and miR-200 family expression. (PMID:18829540)
- TCF8 activates R-Ras, another class of angiogenic regulator, to suppress angiogenesis by a mechanism other than a transcriptional attenuator. (PMID:19116136)
- These findings suggest that Zeb1 represses T-cadherin expression and thus increases the invasive activity of gallbladder cancer. (PMID:19116147)
- DeltaEF1 controls the mesenchymal phenotype and drives erlotinib resistance in HNSCC cells (PMID:19147758)
- E-cadherin, beta-catenin, and ZEB1 have roles in malignant progression of cancer [review] (PMID:19153669)
- The results demonstrate that ZEB-1 directly inhibits SEMA3F expression in lung cancer cells. (PMID:19177200)
- The pro-survival response of neurons, initiated through the rapid induction of p63, is mediated ultimately by the transcriptional repression of a pro-apoptotic isoform of p73 by ZEB1. (PMID:19194497)
- Integral role for TCF8 in the regulation of pathologic angiogenesis, and possible use of TCF8 as a target for therapeutic intervention in cancer. (PMID:19208835)
- These results extend the role of epithelial-to-mesenchymal transition in metastasis to transendothelial migration and implicate ZEB1 and N-cadherin in this process in prostate cancer cells. (PMID:19225155)
- The detailed clinical features of posterior polymorphous corneal dystrophy (PPCD) associated with a novel ZEB1 mutation are supportive of the previously proposed range of phenotype parameters. (PMID:19432861)
- Immunohistochemical analysis of E-cadherin and Zeb-1 in primary tumors confirmed that expression of the two proteins was mutually exclusive. (PMID:19584296)
- Ladybird homeobox 1 (LBX1), a developmentally regulated homeobox gene, directs expression of the known EMT inducers ZEB1, ZEB2, Snail1, and transforming growth factor beta2 (TGFB2). (PMID:19651985)
- CtBP2 monomer interacts with a major CtBP-dependent repressor ZEB and HDAC and that the interaction of the two factors with the CtBP2 monomer was mutually exclusive. (PMID:19754958)
- these results indicate that ZEB1 and AR regulate each other to promote cell migration in triple negative breast cancer cells (PMID:19921427)
- report that ZEB1 not only promotes tumour cell dissemination, but is also necessary for the tumour-initiating capacity of pancreatic and colorectal cancer cells. (PMID:19935649)
- ZEB1 mutations may account for posterior polymorphous corneal dystrophy in 18 to 30% of cases, with the majority of the mutations in exons 5 and 7. (PMID:19997581)
Cross-species orthologs
4 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | zeb1b | ENSDARG00000013207 |
| danio_rerio | zeb1a | ENSDARG00000016788 |
| mus_musculus | Zeb1 | ENSMUSG00000024238 |
| rattus_norvegicus | Zeb1 | ENSRNOG00000017863 |
Paralogs (1): ZEB2 (ENSG00000169554)
Protein
Protein identifiers
Zinc finger E-box-binding homeobox 1 — P37275 (reviewed: P37275)
Alternative names: NIL-2-A zinc finger protein, Negative regulator of IL2, Transcription factor 8
All UniProt accessions (5): P37275, F6TDF5, F6U0D0, H0YMD3, H0YND9
UniProt curated annotations — full annotation on UniProt →
Function. Acts as a transcriptional repressor. Inhibits interleukin-2 (IL-2) gene expression. Enhances or represses the promoter activity of the ATP1A1 gene depending on the quantity of cDNA and on the cell type. Represses E-cadherin promoter and induces an epithelial-mesenchymal transition (EMT) by recruiting SMARCA4/BRG1. Represses BCL6 transcription in the presence of the corepressor CTBP1. Positively regulates neuronal differentiation. Represses RCOR1 transcription activation during neurogenesis. Represses transcription by binding to the E box (5’-CANNTG-3’). In the absence of TGFB1, acts as a repressor of COL1A2 transcription via binding to the E-box in the upstream enhancer region.
Subunit / interactions. Interacts (via N-terminus) with SMARCA4/BRG1.
Subcellular location. Nucleus.
Tissue specificity. Colocalizes with SMARCA4/BRG1 in E-cadherin-negative cells from established lines, and stroma of normal colon as well as in de-differentiated epithelial cells at the invasion front of colorectal carcinomas (at protein level). Expressed in heart and skeletal muscle, but not in liver, spleen, or pancreas.
Post-translational modifications. Ubiquitinated, leading to degradation in a proteasome-dependent manner. Deubiquitinated by USP51, leading to stabilization.
Disease relevance. Corneal dystrophy, posterior polymorphous, 3 (PPCD3) [MIM:609141] A subtype of posterior corneal dystrophy, a disease characterized by alterations of Descemet membrane presenting as vesicles, opacities or band-like lesions on slit-lamp examination and specular microscopy. Affected patient typically are asymptomatic. The disease is caused by variants affecting the gene represented in this entry. Corneal dystrophy, Fuchs endothelial, 6 (FECD6) [MIM:613270] A corneal disease caused by loss of endothelium of the central cornea. It is characterized by focal wart-like guttata that arise from Descemet membrane and develop in the central cornea, epithelial blisters, reduced vision and pain. Descemet membrane is thickened by abnormal collagenous deposition. The disease is caused by variants affecting the gene represented in this entry.
Similarity. Belongs to the delta-EF1/ZFH-1 C2H2-type zinc-finger family.
Isoforms (5)
| UniProt ID | Names | Canonical? |
|---|---|---|
| P37275-1 | 1 | yes |
| P37275-2 | 2 | |
| P37275-3 | 3 | |
| P37275-4 | 4 | |
| P37275-5 | 5 |
RefSeq proteins (40): NP_001121600, NP_001167564, NP_001167565, NP_001167566, NP_001167567, NP_001310570, NP_001310571, NP_001310572, NP_001310573, NP_001310574, NP_001310575, NP_001310576, NP_001310577, NP_001310578, NP_001310579, NP_001310580, NP_001310581, NP_001310582, NP_001310583, NP_001310584, NP_001310585, NP_001310586, NP_001310587, NP_001310588, NP_001310589, NP_001310590, NP_001310591, NP_001310592, NP_001310593, NP_001310594, NP_001310595, NP_001310600, NP_001310601, NP_001310602, NP_001310603, NP_001310604, NP_001310605, NP_001310606, NP_001310607, NP_110378 (=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR001356 | HD | Domain |
| IPR008598 | Di19_Zn-bd | Domain |
| IPR009057 | Homeodomain-like_sf | Homologous_superfamily |
| IPR013087 | Znf_C2H2_type | Domain |
| IPR036236 | Znf_C2H2_sf | Homologous_superfamily |
| IPR051574 | ZnF_E-box_Homeobox | Family |
Pfam: PF00096, PF05605
UniProt features (88 total): sequence conflict 17, cross-link 15, compositionally biased region 11, modified residue 11, sequence variant 11, zinc finger region 7, region of interest 7, splice variant 4, helix 3, chain 1, DNA-binding region 1
Structure
Experimental structures (PDB)
1 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 2E19 | SOLUTION NMR |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P37275-F1 | 48.64 | 0.01 |
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 (26): 31, 33, 313, 322, 642, 679, 686, 693, 700, 702, 704, 186, 195, 307, 331, 335, 347, 347, 439, 493 …
Function
Pathways and Gene Ontology
Reactome pathways
3 pathways
| ID | Pathway |
|---|---|
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling |
| R-HSA-9764725 | Negative Regulation of CDH1 Gene Transcription |
| R-HSA-9926550 | Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition |
MSigDB gene sets: 563 (showing top):
GOBP_REGULATION_OF_CELL_ACTIVATION, CREL_01, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, RRAGTTGT_UNKNOWN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, GOBP_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, GCANCTGNY_MYOD_Q6
GO Biological Process (28): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), pattern specification process (GO:0007389), central nervous system development (GO:0007417), regulation of mesenchymal cell proliferation (GO:0010464), negative regulation of keratinocyte proliferation (GO:0010839), regulation of transforming growth factor beta receptor signaling pathway (GO:0017015), cell differentiation (GO:0030154), regulation of T cell differentiation in thymus (GO:0033081), keratinocyte proliferation (GO:0043616), negative regulation of endothelial cell differentiation (GO:0045602), positive regulation of neuron differentiation (GO:0045666), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), embryonic camera-type eye morphogenesis (GO:0048596), embryonic skeletal system morphogenesis (GO:0048704), semicircular canal morphogenesis (GO:0048752), regulation of smooth muscle cell differentiation (GO:0051150), cartilage development (GO:0051216), cellular response to amino acid stimulus (GO:0071230), cochlea morphogenesis (GO:0090103), nervous system development (GO:0007399), cell population proliferation (GO:0008283), negative regulation of epithelial cell differentiation (GO:0030857), animal organ development (GO:0048513), embryonic morphogenesis (GO:0048598), epithelial cell proliferation (GO:0050673), negative regulation of epithelial cell proliferation (GO:0050680)
GO Molecular Function (10): 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), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), E-box binding (GO:0070888), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)
GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829)
Reactome top-level categories
Rollup of top-3 pathways:
| Category | Pathways |
|---|---|
| Signaling by Interleukins | 1 |
| Regulation of CDH1 Gene Transcription | 1 |
| MITF-M-dependent gene expression | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| regulation of transcription by RNA polymerase II | 3 |
| transcription by RNA polymerase II | 3 |
| regulation of DNA-templated transcription | 3 |
| RNA polymerase II transcription regulatory region sequence-specific DNA binding | 3 |
| cellular anatomical structure | 3 |
| binding | 2 |
| negative regulation of DNA-templated transcription | 1 |
| multicellular organism development | 1 |
| multicellular organismal process | 1 |
| nervous system development | 1 |
| system development | 1 |
| mesenchymal cell proliferation | 1 |
| regulation of cell population proliferation | 1 |
| regulation of keratinocyte proliferation | 1 |
| keratinocyte proliferation | 1 |
| negative regulation of epithelial cell proliferation | 1 |
| transforming growth factor beta receptor signaling pathway | 1 |
| regulation of transmembrane receptor protein serine/threonine kinase signaling pathway | 1 |
| regulation of cellular response to transforming growth factor beta stimulus | 1 |
| cellular developmental process | 1 |
| T cell differentiation in thymus | 1 |
| regulation of T cell differentiation | 1 |
| epithelial cell proliferation | 1 |
| negative regulation of epithelial cell differentiation | 1 |
| endothelial cell differentiation | 1 |
| regulation of endothelial cell differentiation | 1 |
| neuron differentiation | 1 |
| positive regulation of cell differentiation | 1 |
| regulation of neuron differentiation | 1 |
| DNA-templated transcription | 1 |
| negative regulation of RNA biosynthetic process | 1 |
| positive regulation of DNA-templated transcription | 1 |
| embryonic camera-type eye development | 1 |
| embryonic eye morphogenesis | 1 |
| camera-type eye morphogenesis | 1 |
| embryonic organ morphogenesis | 1 |
| skeletal system morphogenesis | 1 |
| embryonic skeletal system development | 1 |
| tube morphogenesis | 1 |
| inner ear morphogenesis | 1 |
Protein interactions and networks
STRING
3848 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| ZEB1 | CTBP1 | Q13363 | 992 |
| ZEB1 | HDAC1 | Q13547 | 969 |
| ZEB1 | CDH1 | P12830 | 961 |
| ZEB1 | SMARCA4 | P51532 | 949 |
| ZEB1 | CTBP2 | P56545 | 939 |
| ZEB1 | SMAD3 | P84022 | 930 |
| ZEB1 | VIM | P08670 | 913 |
| ZEB1 | DNMT1 | P26358 | 897 |
| ZEB1 | TWIST1 | Q15672 | 890 |
| ZEB1 | CDH2 | P19022 | 882 |
| ZEB1 | COL8A2 | P25067 | 871 |
| ZEB1 | HDAC2 | Q92769 | 869 |
| ZEB1 | SMAD2 | Q15796 | 865 |
| ZEB1 | EP300 | Q09472 | 864 |
| ZEB1 | CTNNB1 | P35222 | 856 |
IntAct
46 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| HDAC2 | KDM1A | psi-mi:“MI:0914”(association) | 0.890 |
| ZEB1 | CTBP1 | psi-mi:“MI:0915”(physical association) | 0.860 |
| CTBP1 | ZEB2 | psi-mi:“MI:0914”(association) | 0.800 |
| CTBP1 | KDM1A | psi-mi:“MI:0914”(association) | 0.790 |
| CTBP1 | CBX4 | psi-mi:“MI:0914”(association) | 0.700 |
| EN1 | NFIB | psi-mi:“MI:2364”(proximity) | 0.470 |
| CDK6 | ZEB1 | psi-mi:“MI:0217”(phosphorylation reaction) | 0.440 |
| IFNL1 | ZEB1 | psi-mi:“MI:0914”(association) | 0.350 |
| SYNCRIP | ARHGAP32 | psi-mi:“MI:0914”(association) | 0.350 |
| DCAF15 | ARNT | psi-mi:“MI:0914”(association) | 0.350 |
| CTBP1 | TAF15 | psi-mi:“MI:0914”(association) | 0.350 |
| CTBP1 | GSN | psi-mi:“MI:0914”(association) | 0.350 |
| CTBP2 | ZEB2 | psi-mi:“MI:0914”(association) | 0.350 |
| HDAC1 | psi-mi:“MI:0914”(association) | 0.350 | |
| HDAC2 | psi-mi:“MI:0914”(association) | 0.350 | |
| RBBP4 | KPNA3 | psi-mi:“MI:0914”(association) | 0.350 |
| NFIB | psi-mi:“MI:0914”(association) | 0.350 | |
| INSR | ATOX1 | psi-mi:“MI:0914”(association) | 0.350 |
| TP53BP1 | PSMD14 | psi-mi:“MI:2364”(proximity) | 0.270 |
| STK38L | SH3PXD2B | psi-mi:“MI:2364”(proximity) | 0.270 |
| STK38L | CCDC187 | psi-mi:“MI:2364”(proximity) | 0.270 |
| CTBP1 | SEC16A | psi-mi:“MI:2364”(proximity) | 0.270 |
| SRF | ZNF292 | psi-mi:“MI:2364”(proximity) | 0.270 |
| ELF2 | SETD1A | psi-mi:“MI:2364”(proximity) | 0.270 |
| FEV | TAF4 | psi-mi:“MI:2364”(proximity) | 0.270 |
BioGRID (277): ZEB1 (Affinity Capture-Western), ZEB1 (Affinity Capture-Western), ZEB1 (Affinity Capture-Western), EP300 (Affinity Capture-Western), ZEB1 (Biochemical Activity), CTBP2 (Affinity Capture-Western), CTBP1 (Affinity Capture-Western), SIRT1 (Affinity Capture-Western), USP7 (Affinity Capture-Western), CHEK1 (Affinity Capture-Western), ZEB1 (Affinity Capture-Western), ZEB1 (Reconstituted Complex), ATM (Affinity Capture-Western), ZEB1 (Biochemical Activity), ZEB1 (Affinity Capture-MS)
ESM2 similar proteins: A0A0R4IYX6, A0A1L8H0H2, A5X7A0, A7XYJ6, E1BE02, F6NSX9, F8VPJ6, O35914, O57415, P37275, P59598, P59759, Q03172, Q13029, Q2KHR2, Q3UH06, Q5EXX3, Q5R7F2, Q5ZIE8, Q5ZLR2, Q62947, Q63755, Q64318, Q6NRM0, Q6ZPY7, Q76L83, Q7LBC6, Q7YR76, Q80VX4, Q86V15, Q8BHZ4, Q8BLG0, Q8BRH4, Q8BX22, Q8BZ32, Q8C0C0, Q8IZQ8, Q8NEZ4, Q8R5I7, Q8VIM5
Diamond homologs: A0A1L8FFY5, A0A1W2PPF3, A0JNI8, A1L0Z1, A1L2U9, A2PZF9, B0XS89, B1WAZ8, B1WBU4, G5EBU4, G5EC36, G5EE86, G5EEA1, O60315, O62836, O73590, P08048, P09088, P10925, P17010, P17012, P20154, P20662, P20912, P28166, P29674, P31362, P31363, P34764, P34765, P36197, P36198, P36200, P37137, P37275, P42571, P48742, P49335, P50458, P52739
SIGNOR signaling
24 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| SMARCA4 | up-regulates | ZEB1 | binding |
| DAB2IP | “down-regulates quantity by repression” | ZEB1 | “transcriptional regulation” |
| SALL4 | “up-regulates quantity by expression” | ZEB1 | “transcriptional regulation” |
| ZEB1 | “down-regulates quantity by repression” | CDH1 | “transcriptional regulation” |
| ZEB1 | “down-regulates quantity by repression” | EPCAM | “transcriptional regulation” |
| ZEB1 | “down-regulates quantity by repression” | GRHL2 | “transcriptional regulation” |
| GRHL2 | “down-regulates quantity by repression” | ZEB1 | “transcriptional regulation” |
| LBX1 | “up-regulates quantity by expression” | ZEB1 | “transcriptional regulation” |
| ZEB1 | “down-regulates quantity by repression” | FBP1 | “transcriptional regulation” |
| FBXO45 | “down-regulates quantity by destabilization” | ZEB1 | binding |
| “Skp1-Pam E3” | “down-regulates quantity by destabilization” | ZEB1 | polyubiquitination |
| ATM | “up-regulates activity” | ZEB1 | phosphorylation |
| SNAI1 | “up-regulates quantity by expression” | ZEB1 | “transcriptional regulation” |
| hsa-miR-200a-3p | “down-regulates quantity by destabilization” | ZEB1 | “post transcriptional regulation” |
| hsa-mir-200b-3p | “down-regulates quantity by destabilization” | ZEB1 | “post transcriptional regulation” |
| hsa-miR-200c-3p | “down-regulates quantity by destabilization” | ZEB1 | “post transcriptional regulation” |
| hsa-miR-141-3p | “down-regulates quantity by destabilization” | ZEB1 | “post transcriptional regulation” |
| miR-429 | “down-regulates quantity by destabilization” | ZEB1 | “post transcriptional regulation” |
| mir-205 | “down-regulates quantity by destabilization” | ZEB1 | “post transcriptional regulation” |
| ZEB1 | “up-regulates quantity by expression” | VIM | “transcriptional regulation” |
| ZEB1 | “down-regulates quantity by destabilization” | mir-205 | “post transcriptional regulation” |
| ZEB1 | “down-regulates quantity by destabilization” | hsa-miR-200a-3p | “post transcriptional regulation” |
| ZEB1 | “down-regulates quantity by destabilization” | hsa-mir-200b-3p | “post transcriptional regulation” |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 55 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.
Reactome pathways:
| Pathway | Partners | Fold | FDR |
|---|---|---|---|
| Negative Regulation of CDH1 Gene Transcription | 8 | 24.7× | 3e-07 |
| Regulation of PTEN gene transcription | 5 | 22.9× | 4e-04 |
| Transcriptional regulation by RUNX1 | 5 | 18.8× | 6e-04 |
| Factors involved in megakaryocyte development and platelet production | 5 | 8.5× | 7e-03 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| positive regulation of miRNA transcription | 5 | 26.9× | 1e-04 |
| transcription by RNA polymerase II | 8 | 10.4× | 1e-04 |
Disease & clinical
Cancer significance
From intOGen — cancer-driver classification: activating (oncogene-like) across 6 cancer types — GBM, LUAD, LUSC, NPC, PCM, SCLC.
Clinical variants and AI predictions
ClinVar
209 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 21 |
| Likely pathogenic | 7 |
| Uncertain significance | 127 |
| Likely benign | 22 |
| Benign | 17 |
Top pathogenic / likely-pathogenic (28)
| Variant ID | HGVS | Classification |
|---|---|---|
| 12631 | NM_001174096.2(ZEB1):c.2919_2920del (p.Gly974fs) | Pathogenic |
| 12632 | NM_001174096.2(ZEB1):c.1351C>T (p.Gln451Ter) | Pathogenic |
| 2028102 | NM_001174096.2(ZEB1):c.400C>T (p.Gln134Ter) | Pathogenic |
| 2033644 | NM_001174096.2(ZEB1):c.1890del (p.Phe630fs) | Pathogenic |
| 2443788 | NM_001174096.2(ZEB1):c.1923G>T (p.Gln641His) | Pathogenic |
| 2443789 | NM_001174096.2(ZEB1):c.2252C>A (p.Ser751Ter) | Pathogenic |
| 2500583 | NM_001174096.2(ZEB1):c.1485dup (p.Glu496fs) | Pathogenic |
| 2571620 | NM_001174096.2(ZEB1):c.1586_1595del (p.Asp529fs) | Pathogenic |
| 2694368 | NM_001174096.2(ZEB1):c.862dup (p.Ile288fs) | Pathogenic |
| 2853981 | NM_001174096.2(ZEB1):c.1972A>T (p.Lys658Ter) | Pathogenic |
| 2856261 | NM_001174096.2(ZEB1):c.482_483del (p.Asn161fs) | Pathogenic |
| 3257351 | NM_001174096.2(ZEB1):c.1812del (p.Asn604fs) | Pathogenic |
| 3726715 | NM_001174096.2(ZEB1):c.2236G>T (p.Glu746Ter) | Pathogenic |
| 374184 | NM_001174096.2(ZEB1):c.976C>T (p.Arg326Ter) | Pathogenic |
| 4204860 | NM_001174096.2(ZEB1):c.787_789delinsTAA (p.His263Ter) | Pathogenic |
| 437319 | NM_001174096.2(ZEB1):c.1579dup (p.Val527fs) | Pathogenic |
| 4713282 | NM_001174096.2(ZEB1):c.1063G>T (p.Glu355Ter) | Pathogenic |
| 4719878 | NM_001174096.2(ZEB1):c.1281_1285del (p.Arg427fs) | Pathogenic |
| 4838558 | NM_001174096.2(ZEB1):c.327dup (p.Asp110fs) | Pathogenic |
| 503716 | NM_001174096.2(ZEB1):c.1335_1338del (p.Ile445fs) | Pathogenic |
| 817540 | NM_001174096.2(ZEB1):c.1696G>T (p.Glu566Ter) | Pathogenic |
| 1032236 | NM_001174096.2(ZEB1):c.504del (p.Gln169fs) | Likely pathogenic |
| 1300210 | NM_001174096.2(ZEB1):c.623dup (p.Tyr208Ter) | Likely pathogenic |
| 1300211 | NM_001174096.2(ZEB1):c.688-1G>A | Likely pathogenic |
| 2434683 | NM_001174096.2(ZEB1):c.1859del (p.Asn620fs) | Likely pathogenic |
| 2444117 | NM_001174096.2(ZEB1):c.831del (p.Ser279fs) | Likely pathogenic |
| 4292343 | NM_001174096.2(ZEB1):c.1448del (p.Pro483fs) | Likely pathogenic |
| 4532235 | NM_001174096.2(ZEB1):c.361C>T (p.Gln121Ter) | Likely pathogenic |
SpliceAI
2877 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 10:31387118:CCTTA:C | acceptor_loss | 1.0000 |
| 10:31387119:CTTAG:C | acceptor_loss | 1.0000 |
| 10:31387120:TTA:T | acceptor_loss | 1.0000 |
| 10:31387121:TA:T | acceptor_loss | 1.0000 |
| 10:31387122:A:AG | acceptor_gain | 1.0000 |
| 10:31387122:A:AT | acceptor_loss | 1.0000 |
| 10:31387123:G:A | acceptor_loss | 1.0000 |
| 10:31387123:G:GG | acceptor_gain | 1.0000 |
| 10:31387123:GGACA:G | acceptor_gain | 1.0000 |
| 10:31388380:G:GT | donor_gain | 1.0000 |
| 10:31461030:A:AG | acceptor_gain | 1.0000 |
| 10:31461033:ACAG:A | acceptor_loss | 1.0000 |
| 10:31461034:C:G | acceptor_gain | 1.0000 |
| 10:31461034:CA:C | acceptor_loss | 1.0000 |
| 10:31461035:A:AC | acceptor_loss | 1.0000 |
| 10:31461035:A:AG | acceptor_gain | 1.0000 |
| 10:31461036:G:GT | acceptor_gain | 1.0000 |
| 10:31461036:GT:G | acceptor_gain | 1.0000 |
| 10:31461036:GTT:G | acceptor_gain | 1.0000 |
| 10:31461036:GTTA:G | acceptor_gain | 1.0000 |
| 10:31461036:GTTAC:G | acceptor_gain | 1.0000 |
| 10:31461233:TGACA:T | donor_gain | 1.0000 |
| 10:31461234:GACA:G | donor_gain | 1.0000 |
| 10:31461234:GACAG:G | donor_gain | 1.0000 |
| 10:31461235:ACA:A | donor_gain | 1.0000 |
| 10:31461236:CA:C | donor_gain | 1.0000 |
| 10:31461237:AGT:A | donor_loss | 1.0000 |
| 10:31461238:G:GG | donor_gain | 1.0000 |
| 10:31461239:T:G | donor_loss | 1.0000 |
| 10:31502346:A:AG | acceptor_gain | 1.0000 |
AlphaMissense
1927 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 10:31510705:T:C | C172R | 1.000 |
| 10:31510795:T:C | C202R | 1.000 |
| 10:31510804:T:A | C205S | 1.000 |
| 10:31510804:T:C | C205R | 1.000 |
| 10:31510805:G:A | C205Y | 1.000 |
| 10:31510805:G:C | C205S | 1.000 |
| 10:31510806:C:G | C205W | 1.000 |
| 10:31510816:T:C | F209L | 1.000 |
| 10:31510817:T:C | F209S | 1.000 |
| 10:31510818:T:A | F209L | 1.000 |
| 10:31510818:T:G | F209L | 1.000 |
| 10:31514642:T:A | C242S | 1.000 |
| 10:31514642:T:C | C242R | 1.000 |
| 10:31514643:G:C | C242S | 1.000 |
| 10:31514644:C:G | C242W | 1.000 |
| 10:31514651:T:C | C245R | 1.000 |
| 10:31514663:T:C | F249L | 1.000 |
| 10:31514664:T:C | F249S | 1.000 |
| 10:31514665:C:A | F249L | 1.000 |
| 10:31514665:C:G | F249L | 1.000 |
| 10:31514682:T:C | L255P | 1.000 |
| 10:31514690:C:A | H258N | 1.000 |
| 10:31514690:C:G | H258D | 1.000 |
| 10:31514691:A:C | H258P | 1.000 |
| 10:31514691:A:G | H258R | 1.000 |
| 10:31514692:C:A | H258Q | 1.000 |
| 10:31514692:C:G | H258Q | 1.000 |
| 10:31514702:C:G | H262D | 1.000 |
| 10:31520143:T:A | C270S | 1.000 |
| 10:31520143:T:C | C270R | 1.000 |
dbSNP variants (sampled 300 via entrez): RS1000033107 (10:31372380 C>T), RS1000036847 (10:31401452 G>A), RS1000039961 (10:31528802 T>C), RS1000070150 (10:31355072 T>C,G), RS1000091758 (10:31528269 T>A,C), RS1000102649 (10:31431976 A>G), RS1000108766 (10:31412590 C>T), RS1000110151 (10:31448794 G>A), RS1000131118 (10:31418609 G>A), RS1000133930 (10:31339918 T>C,G), RS1000137698 (10:31518167 C>A), RS1000151485 (10:31484834 T>C), RS1000157704 (10:31427165 C>T), RS1000158331 (10:31382792 A>G), RS1000175840 (10:31453112 G>C)
Disease associations
OMIM: gene MIM:189909 | disease phenotypes: MIM:613270, MIM:609141, MIM:122000
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| posterior polymorphous corneal dystrophy 3 | Definitive | Autosomal dominant |
| corneal dystrophy, Fuchs endothelial, 6 | Strong | Autosomal dominant |
| corpus callosum, agenesis of | Moderate | Autosomal dominant |
| posterior polymorphous corneal dystrophy | Supportive | Autosomal dominant |
| Fuchs’ endothelial dystrophy | Supportive | Autosomal dominant |
Mondo (8): corneal dystrophy, Fuchs endothelial, 6 (MONDO:0013206), posterior polymorphous corneal dystrophy 3 (MONDO:0012200), posterior polymorphous corneal dystrophy (MONDO:0020364), posterior polymorphous corneal dystrophy 1 (MONDO:0007378), corneal dystrophy (MONDO:0018102), glaucoma (MONDO:0005041), Fuchs’ endothelial dystrophy (MONDO:0005321), corpus callosum, agenesis of (MONDO:0009022)
Orphanet (3): Fuchs endothelial corneal dystrophy (Orphanet:98974), Posterior polymorphous corneal dystrophy (Orphanet:98973), Corneal dystrophy (Orphanet:34533)
HPO phenotypes
32 total (30 of 32 shown, HPO-id order):
| HPO | Term |
|---|---|
| HP:0000006 | Autosomal dominant inheritance |
| HP:0000023 | Inguinal hernia |
| HP:0000483 | Astigmatism |
| HP:0000491 | Keratitis |
| HP:0000501 | Glaucoma |
| HP:0000533 | Chorioretinal atrophy |
| HP:0000563 | Keratoconus |
| HP:0000565 | Esotropia |
| HP:0000572 | Visual loss |
| HP:0000613 | Photophobia |
| HP:0000622 | Blurred vision |
| HP:0000632 | Lacrimation abnormality |
| HP:0000646 | Amblyopia |
| HP:0000662 | Nyctalopia |
| HP:0000969 | Edema |
| HP:0001131 | Corneal dystrophy |
| HP:0003581 | Adult onset |
| HP:0007663 | Reduced visual acuity |
| HP:0007906 | Ocular hypertension |
| HP:0007957 | Corneal opacity |
| HP:0009918 | Ectopia pupillae |
| 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:0012038 | Corneal guttata |
| HP:0012040 | Corneal stromal edema |
| HP:0025358 | Uveal ectropion |
| HP:0030857 | Eye movement-induced pain |
| HP:0032122 | Very low visual acuity |
GWAS associations
5 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST000829_11 | Waist-hip ratio | 6.000000e-06 |
| GCST004278_30 | Pulse pressure | 1.000000e-09 |
| GCST005956_37 | Waist-to-hip ratio adjusted for BMI | 2.000000e-08 |
| GCST005962_50 | Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test) | 2.000000e-06 |
| GCST009158_6 | Uterine fibroids | 2.000000e-10 |
EFO canonical traits (5, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0004343 | waist-hip ratio |
| EFO:0005763 | pulse pressure measurement |
| EFO:0007788 | BMI-adjusted waist-hip ratio |
| EFO:0008007 | age at assessment |
| EFO:0008343 | sex interaction measurement |
MeSH disease descriptors (6)
| Descriptor | Name | Tree numbers |
|---|---|---|
| D061085 | Agenesis of Corpus Callosum | C10.500.034; C16.131.666.034; C23.300.008 |
| D003317 | Corneal Dystrophies, Hereditary | C11.204.236; C11.270.162; C16.320.290.162 |
| D005642 | Fuchs’ Endothelial Dystrophy | C11.204.236.438; C11.270.162.438; C16.320.290.162.410 |
| D005901 | Glaucoma | C11.525.381 |
| C567675 | Corneal Dystrophy, Fuchs Endothelial, 6 (supp.) | |
| C563788 | Corneal Dystrophy, Posterior Polymorphous, 3 (supp.) |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: no
Clinical evidence (CIViC)
Drug × variant × indication: 5 predictive associations from 5 curated evidence items; also 1 prognostic, 1 oncogenic.
| Variant | Therapy | Indication | Effect | Level | CIViC |
|---|---|---|---|---|---|
| ZEB1 Expression | Salinomycin | Mantle Cell Lymphoma | Sensitivity/Response | CIViC D | EID12500 |
| ZEB1 Expression | Salinomycin + Doxorubicin | Mantle Cell Lymphoma | Sensitivity/Response | CIViC D | EID900 |
| ZEB1 Expression | Vincristine | Mantle Cell Lymphoma | Resistance | CIViC D | EID12502 |
| ZEB1 Expression | Oxaliplatin | Colon Cancer | Resistance | CIViC D | EID8086 |
| ZEB1 Expression | Doxorubicin + Cytarabine + Gemcitabine | Mantle Cell Lymphoma | Resistance | CIViC D | EID899 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
CTD chemical–gene interactions
117 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| sodium arsenite | affects methylation, decreases expression, decreases reaction, increases abundance, increases expression (+1 more) | 11 |
| Valproic Acid | affects cotreatment, decreases expression, affects expression | 9 |
| Resveratrol | decreases reaction, increases reaction, increases expression, increases methylation, decreases expression | 5 |
| Estradiol | affects cotreatment, increases expression | 4 |
| Cadmium Chloride | decreases expression, increases abundance, increases expression | 4 |
| trichostatin A | affects cotreatment, decreases expression | 3 |
| Arsenic | decreases reaction, increases abundance, increases expression, affects methylation | 3 |
| Benzo(a)pyrene | affects methylation, decreases expression, increases expression | 3 |
| Cadmium | decreases expression, increases abundance, increases expression, increases methylation, decreases reaction | 3 |
| Doxorubicin | affects cotreatment, decreases expression, affects response to substance | 3 |
| Particulate Matter | decreases expression, increases abundance, increases expression | 3 |
| nickel sulfate | decreases expression, increases expression | 2 |
| methacrylaldehyde | increases oxidation, increases abundance, affects cotreatment, decreases expression | 2 |
| cordycepin | affects cotreatment, increases reaction, decreases expression, decreases localization | 2 |
| entinostat | decreases expression, affects cotreatment | 2 |
| Arsenic Trioxide | increases reaction, increases response to substance, decreases expression | 2 |
| Panobinostat | affects cotreatment, decreases expression | 2 |
| Acrolein | increases abundance, affects cotreatment, decreases expression, increases oxidation | 2 |
| Air Pollutants | affects cotreatment, decreases expression, increases abundance, increases oxidation | 2 |
| Formaldehyde | decreases expression | 2 |
| Ozone | affects cotreatment, decreases expression, increases oxidation, increases abundance | 2 |
| Silver | increases expression | 2 |
| Tretinoin | decreases expression, increases reaction | 2 |
| Cyclosporine | increases expression | 2 |
| aristolochic acid I | decreases expression | 1 |
| FR900359 | decreases phosphorylation | 1 |
| TAK-243 | decreases sumoylation | 1 |
| dicrotophos | decreases expression | 1 |
| thymoquinone | decreases expression, increases reaction | 1 |
| bufotalin | decreases expression | 1 |
Cellosaurus cell lines
9 cell lines: 8 cancer cell line, 1 transformed cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_B8S0 | Abcam HCT 116 ZEB1 KO | Cancer cell line | Male |
| CVCL_B9CL | Abcam MCF-7 ZEB1 KO | Cancer cell line | Female |
| CVCL_B9UJ | Abcam A-549 ZEB1 KO | Cancer cell line | Male |
| CVCL_E1DP | Ubigene THP-1 ZEB1 KO | Cancer cell line | Male |
| CVCL_HD03 | HEK293 eGFP-ZEB1 | Transformed cell line | Female |
| CVCL_TZ11 | HAP1 ZEB1 (-) 1 | Cancer cell line | Male |
| CVCL_XV26 | HAP1 ZEB1 (-) 2 | Cancer cell line | Male |
| CVCL_XV27 | HAP1 ZEB1 (-) 3 | Cancer cell line | Male |
| CVCL_XV28 | HAP1 ZEB1 (-) 4 | Cancer cell line | Male |
Clinical trials (associated diseases)
355 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT00781027 | PHASE4 | COMPLETED | Fuchs’ Torsional Phaco Study |
| NCT03249337 | PHASE4 | RECRUITING | Glanatec(R) for Descemet Stripping in Fuch’s Endothelial Dystrophy |
| NCT05716945 | PHASE4 | RECRUITING | The OPTIMISE Study |
| NCT00061503 | PHASE4 | COMPLETED | Mechanism of Action of TRAVATAN 0.004% in Subjects With Glaucoma or Ocular Hypertension |
| NCT00143208 | PHASE4 | COMPLETED | Evaluation Of Intraocular Pressure Lowering-Effect Of Xalacom In Patients With Poag Or Oh. |
| NCT00224289 | PHASE4 | COMPLETED | Effect of Age on Latanoprost 0.005% in Patients With Glaucoma |
| NCT00273221 | PHASE4 | UNKNOWN | Combined Phacotube vs Phacotrabeculectomy:A Randomized Controlled Trial |
| NCT00329095 | PHASE4 | COMPLETED | An Evaluation of Use of Topical Ocular Hypotensive Medication by Compliance |
| NCT00345046 | PHASE4 | COMPLETED | A Comparison of Three Different Formulations of Prednisolone Acetate 1% |
| NCT00346489 | PHASE4 | COMPLETED | Outcomes of Intraoperative 5-Fluorouracil Versus Mitomycin C |
| NCT00347035 | PHASE4 | TERMINATED | INFLUENCE OF TOPICAL INDOMETHACIN ON HYPOTHENSIVE EFFECT OF BRIMONIDINE |
| NCT00347802 | PHASE4 | COMPLETED | Diurnal Curves With Bimatoprost 0.03% Versus Travoprost 0.004% |
| NCT00347841 | PHASE4 | COMPLETED | Efficacy of Bimatoprost 0.03% in Patients Who Are Low-Responders to Latanoprost |
| NCT00348023 | PHASE4 | COMPLETED | Bimatoprost Monotherapy vs. Dual Therapy With Travoprost and Timolol in Patients With Glaucoma and Ocular Hypertension |
| NCT00348062 | PHASE4 | COMPLETED | A Multicenter Evaluation of Methods to Reduce Hyperemia Associated With Bimatoprost Therapy for Glaucoma or Ocular Hypertension |
| NCT00348400 | PHASE4 | COMPLETED | Brimonidine Purite 0.15% Versus Dorzolamide 2% Used as Adjunctive Therapy to Latanoprost |
| NCT00351429 | PHASE4 | COMPLETED | Study of PGA Suture in Ophthalmology |
| NCT00376974 | PHASE4 | UNKNOWN | The Effect of Education on Patient Compliance |
| NCT00379834 | PHASE4 | COMPLETED | 12-Month Stability of Diurnal IOP Control on Cosopt |
| NCT00382226 | PHASE4 | COMPLETED | IOP-Lowering Efficacy of Brinzolamide 1.0% Added to Travoprost 0.004%/Timolol 0.5% Fixed Combination as Adjunctive Therapy |
| NCT00404729 | PHASE4 | COMPLETED | Neural Conduction Along the Visual Pathways After Oral Treatment With Citicoline in Patients With Optic Nerve Diseases |
| NCT00440011 | PHASE4 | COMPLETED | Bimatoprost 0.03% Versus Travoprost 0.004% in Patients Currently on Latanoprost 0.005% |
| NCT00440141 | PHASE4 | COMPLETED | Brimonidine 0.1% Versus Brinzolamide 1% as Adjunctive Therapy to Latanoprost 0.005% |
| NCT00442312 | PHASE4 | UNKNOWN | Combigan Ophthalmic Solution(Brimonidine 0.2% and Timolol 0.5%)With Latanoprost Compared With Latanoprost Monotherapy |
| NCT00444184 | PHASE4 | COMPLETED | 24-hour Intraocular Pressure Control With Travoprost/Timolol Fixed Combination Versus Travoprost |
| NCT00444665 | PHASE4 | COMPLETED | Examining The Efficacy, Safety And Improved Tolerability Of Travoprost BAK Free Ophthalmic Solution (Travatan-Z) Compared To Prior Prostaglandin Therapy |
| NCT00449098 | PHASE4 | UNKNOWN | Ologen (OculusGen)-Glaucoma MMC Control Trial in India |
| NCT00466479 | PHASE4 | COMPLETED | Brimonidine vs ALTP in Progressing Human Glaucoma |
| NCT00468429 | PHASE4 | UNKNOWN | Subconjunctival Bevacizumab to Prevent Bleb Failure After Glaucoma Filtration Surgery |
| NCT00468988 | PHASE4 | COMPLETED | Short Term Comparative Study of Xalatan With Benzalkonium Chloride vs. Travatan Z Without Benzalkonium Chloride in Healthy Volunteers |
| NCT00471380 | PHASE4 | COMPLETED | A Phase IV Study of Travoprost + Brinzolamide to Treat Glaucoma or Ocular Hypertension |
| NCT00485238 | PHASE4 | UNKNOWN | ALPI vs Medical Therapy Effects on Optic Nerve Structure & Function |
| NCT00486486 | PHASE4 | COMPLETED | 24-hour Intraocular Pressure (IOP) Control With the Bimatoprost/Timolol Fixed Combination |
| NCT00519753 | PHASE4 | COMPLETED | Success of Transitioning Uncontrolled Glaucoma Patients From Prior Mono or Adjunctive Therapy to DuoTrav |
| NCT00541242 | PHASE4 | COMPLETED | Safety and Efficacy of Bimatoprost Compared With Latanoprost in Patients With Glaucoma or Ocular Hypertension |
| NCT00557232 | PHASE4 | COMPLETED | Intraocular Bevacizumab (Avastin) for Rubeosis Iridis |
| NCT00597181 | PHASE4 | TERMINATED | A Clinical Study Comparing the Inflammatory Response of the Ex-Press Mini Shunt to Trabeculectomy |
| NCT00607685 | PHASE4 | COMPLETED | 5FU vs 5FU With Viscoelastic Formulation for the Prevention of Scarring Post-trabeculectomy |
| NCT00626067 | PHASE4 | COMPLETED | Study of Patient Use and Perception of the Travatan Dosing Aid |
| NCT00666237 | PHASE4 | COMPLETED | Primary Tube Versus Trabeculectomy Study |
Related Atlas pages
- Associated diseases: posterior polymorphous corneal dystrophy 3, posterior polymorphous corneal dystrophy, Fuchs’ endothelial dystrophy, corpus callosum, agenesis of, corneal dystrophy, Fuchs endothelial, 6, mantle cell lymphoma, malignant colon neoplasm
- Biomarker drugs (CIViC) (drugs whose response is associated with variants in this gene — CIViC predictive evidence, not targeting): Vincristine, Oxaliplatin
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): colon carcinoma, corneal dystrophy, corneal dystrophy, Fuchs endothelial, 6, corpus callosum, agenesis of, Fuchs’ endothelial dystrophy, glaucoma, malignant colon neoplasm, mantle cell lymphoma, posterior polymorphous corneal dystrophy, posterior polymorphous corneal dystrophy 1, posterior polymorphous corneal dystrophy 3, uterine corpus leiomyoma