pre-miRNA Information | |
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pre-miRNA | mmu-mir-1906-1 |
Genomic Coordinates | chr12: 109544541 - 109544620 |
Description | Mus musculus miR-1906-1 stem-loop |
Comment | None |
RNA Secondary Structure | |
pre-miRNA | mmu-mir-1906-2 |
Genomic Coordinates | chrX: 88759474 - 88759553 |
Synonyms | mmu-mir-1906, Mir1906 |
Description | Mus musculus miR-1906-2 stem-loop |
Comment | None |
RNA Secondary Structure |
Mature miRNA Information | |
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Mature miRNA | mmu-miR-1906 |
Sequence | 48| UGCAGCAGCCUGAGGCAGGGCU |69 |
Evidence | Experimental |
Experiments | Microarray |
Putative Targets |
Gene Information | |||||||||||||||||||||
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Gene Symbol | Fgd4 | ||||||||||||||||||||
Synonyms | 9030023J02Rik, 9330209B17Rik, Frabp, ZFYVE6 | ||||||||||||||||||||
Description | FYVE, RhoGEF and PH domain containing 4 | ||||||||||||||||||||
Transcript | NM_139232 | ||||||||||||||||||||
Expression | |||||||||||||||||||||
Putative miRNA Targets on Fgd4 | |||||||||||||||||||||
3'UTR of Fgd4 (miRNA target sites are highlighted) |
>Fgd4|NM_139232|3'UTR 1 ACTTCAGCAGCTGCTAGTGTGGAGTTTCCAGTAATACACATAGCTCAAGACATCCCCAGCTCTCCTTCCTTGTCTCTTAG 81 CACTTTGCATTGAGAAATATGGTTTCATAAACACATCTTTTGGGGACTTCTTTCATATGTTTATATATAATAAAATCAGT 161 ATGCAGAGCCATTCTTCTGTTGAAGTTCTAAAATAATGTGGAAAATGGAACCTTTTTGATAAGCTATTCCTTAACTGTGT 241 ATGTTTGCCTTGAGTGGGTTAAAAAATGTTAACTGTCGAATCACTACCTGGTTATAATGGGCCTTTCATTTAAGAAATCC 321 TTCATTGTCTTGTTCACATGTAGAACTTGTAAGAGTGTGAAAAATATACCTCCATGTAACCAAAATAGATCTATGGTAAA 401 AAGTACAGGGACAGTTTAGAGTATTGTATGAACTTGTCTAGTTTGTAAGTCTCATGCTATGTAAATAGTTTCTGTTCTTA 481 TACAACACAAAAAATTATAGGTTCCTGATGTTGATACTTTTTGACTTAATATAATACTTGTTTTGTAGAATTACTCCTAA 561 TAATAAAATATCTAAAATACAAATCAATTTGCCTGTATATAATATTGAAAATAAGTATGAATATGTCAGCTTTCTCTTCA 641 GCTTTAGTTTTGTTTTCACTCTGGTTAATTCTTTAAATATAAAACCTATTTTATTTCTAAACTTAGCAGTGTTCTAAATT 721 TAAGAAAAATTGGTAAGTTATGTTGAACTGATTAGAATCTAAGTGTATTGATATTTTTATAGTAAAAAAGAGTAATTTAT 801 GTGGTGTCAGATATAGTGTGAATTTCAACAGTATTTTTAGAGTACTATTTTTCTTTTGTTCTGTACCTATTTAAAACAGT 881 GCCTCTCTTAGAAGGTGCTATTAATTCTTATTTAGATAAAAGATGAGGGTTTAGTAAATAGTAACTAAACATTATTATTT 961 TTAACTACTCTGCTTATTCTCAACTTAAGTGCACTTTGGTCACAGAGATTAAAATGTATGGCTTACTTTACATTTTATAT 1041 TAACATAATTGTCATGGTAATTTAATGTCAACATATGCAAAAACTTCCTAAAACTATATAAGACATCTGACCTTATAGAG 1121 CCCTGGGATATATGGAAGACGCTGGTTTACTGTTTACTGTCCTCCTTTCCATTGGACTGTTATGGACGGGTAAATGAGGA 1201 CAACATCTAATAAACACAAGGTGGCTGGGTGAGCTTTCCTTCTGTCAGCTACAAAGCGGAGCTCATGCGTGTGCCAGCTT 1281 ATCTGGGAGAAGAGAGTTATTAGTAAAGGAAATTTATGCTTAATCATTCACTAGAAAAGATAGATGAAACCAGGATTTCA 1361 GAATCAATAATGGCAGATTTCTATGAGATGGGAAGCACTAAAGAAACTGCAGAATTCTCCCTTTTTATCCCATGGACTCT 1441 CAGATGAACTATGGCTGTCTATTAGGTTGTGCTTGTGACTAAAATCTTATGTTGAGTTTACTGTTTAAGTTAATACTTTT 1521 CTCATATTAGACTTTTTTCCTTTCTTTTCCATTCTCCAAACATTACCACTTTTACTGTACTGTTTACTAGGAATCCATAG 1601 AATGTCTTCACTACACACAATCTTTAAGGGCTACACTTGAGATGTAGAGTACAATTTATCAGAAATTGAGACCACCATAC 1681 ATTTATACACCTCATGTTGCACAAGAAACGTCTCATTTTTTTTCTACTCCAAAGGAGCAAGGGAACCAATTAGGTTGCTT 1761 TCCTCCATGAAATACCAGACATGAACATTAACATTAAACCATCTATTTAGAATCACTAATGGGCAAAACACAAAGCTATC 1841 TCCTTATTCCCTACTAAATGAGAGTCATATAGAAAGAAATTGTACATTGTTTCTCTTTTCTAGTTGTCAGCATTGATGCT 1921 GTGTTTGAGTGGGAGGAAAGAAACCAGGTGTGAAGGGTACCTATTGATAAAATTAAACAATAACTATACATCTTACTTTA 2001 TTTTTCATATTTCAAGAAAAGAAAAGCAGTAAATATGTAGAATGACTATCAGAATAAGGATGACTTCTGTAAATATAAGC 2081 AGAATAATGAGTGAACTGTCTCACTTAGAAGATTTATGTCAGATAATATTTAAAAAAAAAACTATTTGATCAGCAAGAAG 2161 AGTACATGTTTGCCTACCAGCAAATTCTTGAATAGAAGGAATATGATTAGATATTCAGTGTAGTTCAACTTAGATTATTG 2241 AAAGGATACTCATAAAAAGAATGTTAGCATGCTTCTAGTGTTCATTCAGTAAGGAGTGTGAGTGCCAGAAGAGGATCTTC 2321 TCTGGTTCTCACCTTTACTTCTCCCCACACTGAGCCAAGCACAAACCACTTTCCCCATCTCTCTCAAAATAACCACAAAT 2401 ACTTTTAGTAGGAGAAAAAAGTAATAGAATAATATTAGTTACTTATTAAGAACTCAACTCTGGGGCTAAGGAGAATTCTA 2481 TGCAAGGATGAGAAACAGTTCAGACAGGTCTCCGGAGACCACATAAAGGCCAGGCAAGCAAGGGCAACAGAGGTGGGGCC 2561 AGGAAGTTTTGGTGAAGGTGCTCTATCCAGGCAAGTCAGAGCAGCGAGTGCAGGAACAGTAAGTAACCTTGCCTCAATGA 2641 TGAGGTAGAGAGGCACCAAGGAAGTCACCTGACATAGCCTCAGATCTCTCCACATTTGCACAGTTCCCTAAATATATGTG 2721 AACACACATGCATGGACAGTGTGCATGCACATACACATTAAAAAATCTAATTCAAATAAACTCCAATCCAAGAGGTTGTT 2801 AGAATAACTAACCTCTTTTTGAGATAAGTAGGGTTTCATGATAAACTGAGCCTGAACATAGTATCAGTTCCTTTCCTGAT 2881 CAAATAAATGTTTCATATGGTTCTTAATTTGTTATTTTCTCTAGCTTAGTGTGTTCAAAAGTAATCTTTAAGAAAAATGT 2961 CCTTCCTTCAAATTTAAGAAAATATTTCTTTGGTAAAATTGTTATTCATTCAAAGCATTTCAACTTTCAACATAATTGTT 3041 GCTTTTGTTGAAAGTCTACCATTTGGAAAAGGTGAGATGTGGTACATGCTTTTATCTAAACTTTTATGTGGAGTTCAATA 3121 ATGAAAAATGCCACTAGCCACTTTTGTAATAATACCAAGCAATAAAACTCTCCAGTATGAGTTTATACCAAAAGTTTAAC 3201 ATGAAGGCCCTAAGCTACAGCATATAGAGAATCAACTTCTGAGAAGTGATATGATAGTCCAAATTGCTGAGCACAGGGGA 3281 AAGAAGGAAGGCATCGTTCCATGGCTTCAGGCATATCAACTGTGTTTAATTTCTTTTTTTTTTAGATTTATTTATTTTAT 3361 GTATATGAGTACACTGTCACTATCTTTAGACACACCCGAAGAAGGCATCAGATCCCATTGCAGATGGTTGTGAACCACCA 3441 TGCGGTTGCTGGGAATTGAACTCAGGACCTCTTAATTGCTGAGCCATCACTCTAGCCTTGTGTTTAATTTCTACAAAGGC 3521 TATGTATAATGAAGCAGTTTGTTTGCTCTGCTCTGTTTTATCAGCTGTGTTGTACATTTCTGTGAATTGAATTCAACATA 3601 AAGGTTGCCATACTGTCTTCACTGGATTACCTACACCATTTTTTAAATATAGGAATTAACCTTGTAAATGTTCCCTGCTG 3681 AATTTTCTAAACAAGAGTATATGTTGCCATCAGAACTGTTTAACTATAATTCCATGGTACTTCAGGGTTGTTGAAGAGCC 3761 ACTGATGCCTTCTAAAATCCTCTACTCAAAAATACTTCTGGAGTTCATGATTCTGTTTTTTGGGGTATTTGGGGAGATTG 3841 ATTGTTTTCCTCCTTTTGGTTGAGGTGGAAGGGTTTTCCCTCCTTCAGTTATTTTCAGATATCATTTGTTTATTTCTAAA 3921 GCTTTAACTTATTCAGAGTGTATTGTCTGAAATGGATTCTTAATCCTCATATCTGTCAGTGTGTTGTCATGGCAAATGAG 4001 CATGAATAAGAGTAAATCAATTCCCAGAAAGCACAGGTCTTATTTATCTCTGTTGTTTTAAGAGTAGAAGGTAACTTAGC 4081 TTTCCTACATCACATGATAAGCACATGGTATGTATAATCTAAAATTTGAAAGACAGAACAATCTTAGTGTTTTATTTAAT 4161 GTTGTGATCTTCAAGAATGTATGAATATAAGAACTGAGGCTAAAGAGTTCCTCTTATTAGAGTTACATTCACATTTGTAG 4241 TGGATCCTGTCACTTTTTCATTCTAAGTTTAATTAGAATCAAGTTTTTTATTTTCATATAACTATCAAACTATAGGTTCC 4321 CTAGATTTTAAAAGAAAAGCATTAGACTACTAGATCTATCTAAATACTCTCTGTGACTTTATATGTATAAATGTACAAAT 4401 TATAAATCTTCAATTCTCACCAAAGAACAAAATGTTATGTAAAATTTAATTTAAGTATTTTAACAAAATTATTCACATGT 4481 GTTTTTAATGTTATAATTCATCTTTACCCAAGCCCATCAGTCTTGCTAGGTTACAGGAAGAGGCAATGTTGCTTTTGTTG 4561 CAGGTATAGAGAGAGCACCTACCTTAGCACATGAAAGGAATGAATGGAGCTGGATAAATGGGCTGACTACTTGTATCCAT 4641 GTGAACTGCTCGAGAGAAATAAGTTAGAAGATGCCTATGTACTTGTTGGTGGATGAAATCCTTGTGCTCAGGATTTGACC 4721 TTGGCATCTAAATTATACATGATATTATCTTATCATTACTTTATTTCTTCTTTAAGCTTTTACAAAGTAATCTCATTCTA 4801 TAAGCCATTTTTCTGCTATTTTTCACTCTAAAGTCAACTTTCTAAGAGAAGGGAATGGCTAAATGCTGTGTCTTTTCTGT 4881 ATTTCAAGATAAAATAACACATGGCTTCTACAAGATAGTTTATTTGTTGGAAGTGGGGGTCACTGAAAGTTACATAAAGA 4961 TCATACTTTGCCCTAAAATTCATTGTGATCAATTTGATAAAAAAAATTAAATCAAATTTTAGTATATTTTAATAAGTGAA 5041 TACTAAATGCATCAAGTAAATACAGACCTTATAGCCCATTATGATGAGAAAATTGAATTGTGTATTATGAAATATGAAGA 5121 CTCAAATATATACTATATATTATTTAACATTTAATCATTCATATATAAAACCAAACTGCCATTTCATATTTTAAGAGACA 5201 ATTAATTGTTTTGTTTTGGTTTTGGTTTTTTGGTTTTTCGAGACAAGGTTTCTCTGTATAGCTGTCCTGGAACTCACTTT 5281 GTTGACCAGGCTGGCCTCGAACTCAGAAATCCACCTGCCTCTGCCTCGAGTGCTGGGATTAAAGGTGTGTGCCACCACAC 5361 CCAGTGCTAATTGTTATTTAAAAAACTAAGAATTATTTTGATTTTTCTTTTGACATGTTTACTGAGTTTCAAAGGGCACA 5441 TCAGAATTTTATAGTTGTGAAAATATAAACATCCCTATTTTGCAGTGGTGTGAATGTACAATACTTAGATATGCTGTATA 5521 TATAGTGTAACATCTGTATATTTAATCATAAAGGCAGATAATTGAAAACATTGTAAAATTAAGCACTTCAATTCTTGTTA 5601 AATATGAAACATTTGTATCTTGTAAATAAAGACATCCTTAAATTGGTT Target sites
Provided by authors
Predicted by miRanda
DRVs
SNPs
DRVs & SNPs
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miRNA-target interactions (Predicted by miRanda) |
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Experimental Support 1 for Functional miRNA-Target Interaction | |
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miRNA:Target | ---- |
Validation Method |
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Conditions | mESCs |
Location of target site | 3'UTR |
Tools used in this research | TargetScan , miRTarCLIP , Piranha |
Original Description (Extracted from the article) |
...
HITS-CLIP data was present in GSM622570. RNA binding protein: AGO2. Condition:WT1A
HITS-CLIP data was present in GSM622571. RNA binding protein: AGO2. Condition:WT1B
HITS-CLIP data was present in GSM622574. RNA binding protein: AGO2. Condition:KO2
... - Leung AK; Young AG; Bhutkar A; Zheng GX; et al., 2011, Nature structural & molecular biology. |
Article |
- Leung AK; Young AG; Bhutkar A; Zheng GX; et al. - Nature structural & molecular biology, 2011
MicroRNAs (miRNAs) are 19-22-nucleotide noncoding RNAs that post-transcriptionally regulate mRNA targets. We have identified endogenous miRNA binding sites in mouse embryonic stem cells (mESCs), by performing photo-cross-linking immunoprecipitation using antibodies to Argonaute (Ago2) followed by deep sequencing of RNAs (CLIP-seq). We also performed CLIP-seq in Dicer(-)/(-) mESCs that lack mature miRNAs, allowing us to define whether the association of Ago2 with the identified sites was miRNA dependent. A significantly enriched motif, GCACUU, was identified only in wild-type mESCs in 3' untranslated and coding regions. This motif matches the seed of a miRNA family that constitutes ~68% of the mESC miRNA population. Unexpectedly, a G-rich motif was enriched in sequences cross-linked to Ago2 in both the presence and absence of miRNAs. Expression analysis and reporter assays confirmed that the seed-related motif confers miRNA-directed regulation on host mRNAs and that the G-rich motif can modulate this regulation.
LinkOut: [PMID: 21258322]
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CLIP-seq Support 1 for dataset GSM4656410 | |
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Method / RBP | HITS-CLIP / AGO |
Cell line / Condition | mouse liver / e185 rep2 |
Location of target site | NM_139234 | 3UTR | GCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCU |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Accession Series | GSE153876 |
CLIP-seq Viewer | Link |
CLIP-seq Support 2 for dataset GSM4751756 | |
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Method / RBP | HITS-CLIP / AGO |
Cell line / Condition | adipose tissue / RNA sequencing of iBAT 1 |
Location of target site | NM_139234 | 3UTR | GCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCU |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Accession Series | GSE142677 |
CLIP-seq Viewer | Link |
CLIP-seq Support 3 for dataset GSM4751757 | |
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Method / RBP | HITS-CLIP / AGO |
Cell line / Condition | adipose tissue / RNA sequencing of iBAT 2 |
Location of target site | NM_139234 | 3UTR | GCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Accession Series | GSE142677 |
CLIP-seq Viewer | Link |
CLIP-seq Support 4 for dataset GSM4751758 | |
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Method / RBP | HITS-CLIP / AGO |
Cell line / Condition | adipose tissue / RNA sequencing of iBAT 3 |
Location of target site | NM_139234 | 3UTR | GCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Accession Series | GSE142677 |
CLIP-seq Viewer | Link |
CLIP-seq Support 5 for dataset GSM4751759 | |
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Method / RBP | HITS-CLIP / AGO |
Cell line / Condition | adipose tissue / RNA sequencing of iBAT 4 |
Location of target site | NM_139234 | 3UTR | UGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Accession Series | GSE142677 |
CLIP-seq Viewer | Link |
CLIP-seq Support 6 for dataset GSM4751760 | |
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Method / RBP | HITS-CLIP / AGO |
Cell line / Condition | adipose tissue / RNA sequencing of eWAT 1 |
Location of target site | NM_139234 | 3UTR | GCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Accession Series | GSE142677 |
CLIP-seq Viewer | Link |
CLIP-seq Support 7 for dataset GSM4751761 | |
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Method / RBP | HITS-CLIP / AGO |
Cell line / Condition | adipose tissue / RNA sequencing of eWAT 2 |
Location of target site | NM_139234 | 3UTR | UGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Accession Series | GSE142677 |
CLIP-seq Viewer | Link |
CLIP-seq Support 8 for dataset GSM4751762 | |
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Method / RBP | HITS-CLIP / AGO |
Cell line / Condition | adipose tissue / RNA sequencing of eWAT 3 |
Location of target site | NM_139234 | 3UTR | GCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Accession Series | GSE142677 |
CLIP-seq Viewer | Link |
CLIP-seq Support 9 for dataset GSM622570 | |
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Method / RBP | HITS-CLIP / AGO2 |
Cell line / Condition | mESCs / WT1A |
Location of target site | NM_139234 | 3UTR | GCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGC |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 21258322 / GSE25310 |
CLIP-seq Viewer | Link |
CLIP-seq Support 10 for dataset GSM622571 | |
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Method / RBP | HITS-CLIP / AGO2 |
Cell line / Condition | mESCs / WT1B |
Location of target site | NM_139234 | 3UTR | GCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCU |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 21258322 / GSE25310 |
CLIP-seq Viewer | Link |
CLIP-seq Support 11 for dataset GSM622574 | |
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Method / RBP | HITS-CLIP / AGO2 |
Cell line / Condition | mESCs / KO2 |
Location of target site | NM_139234 | 3UTR | GCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCUGCU |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 21258322 / GSE25310 |
CLIP-seq Viewer | Link |
27 mmu-miR-1906 Target Genes:
Functional analysis:
ID | Target | Description | Validation methods | |||||||||
Strong evidence | Less strong evidence | |||||||||||
MIRT578439 | Irgq | immunity-related GTPase family, Q | 2 | 10 | ||||||||
MIRT578971 | Dhdh | dihydrodiol dehydrogenase (dimeric) | 2 | 4 | ||||||||
MIRT580446 | Tln2 | talin 2 | 2 | 2 | ||||||||
MIRT582494 | Mbtps2 | membrane-bound transcription factor peptidase, site 2 | 2 | 2 | ||||||||
MIRT587588 | Cox15 | cytochrome c oxidase assembly protein 15 | 2 | 2 | ||||||||
MIRT589524 | Mtf1 | metal response element binding transcription factor 1 | 2 | 2 | ||||||||
MIRT591281 | Klc1 | kinesin light chain 1 | 2 | 4 | ||||||||
MIRT591935 | Ddx19b | DEAD (Asp-Glu-Ala-Asp) box polypeptide 19b | 2 | 2 | ||||||||
MIRT592084 | Sorcs2 | sortilin-related VPS10 domain containing receptor 2 | 2 | 2 | ||||||||
MIRT592206 | Mapkap1 | mitogen-activated protein kinase associated protein 1 | 2 | 4 | ||||||||
MIRT592349 | Armcx6 | armadillo repeat containing, X-linked 6 | 2 | 4 | ||||||||
MIRT592351 | Angel1 | angel homolog 1 | 2 | 2 | ||||||||
MIRT592365 | 4930444A02Rik | protein-O-mannose kinase | 2 | 2 | ||||||||
MIRT592427 | Spsb4 | splA/ryanodine receptor domain and SOCS box containing 4 | 2 | 2 | ||||||||
MIRT592671 | Itgav | integrin alpha V | 2 | 2 | ||||||||
MIRT592712 | Fbxo21 | F-box protein 21 | 2 | 4 | ||||||||
MIRT593155 | Itsn1 | intersectin 1 (SH3 domain protein 1A) | 2 | 2 | ||||||||
MIRT593662 | Spen | SPEN homolog, transcriptional regulator (Drosophila) | 2 | 2 | ||||||||
MIRT593976 | Cdc14b | CDC14 cell division cycle 14B | 2 | 2 | ||||||||
MIRT597931 | Pacsin2 | protein kinase C and casein kinase substrate in neurons 2 | 2 | 2 | ||||||||
MIRT597949 | Opa1 | OPA1, mitochondrial dynamin like GTPase | 2 | 2 | ||||||||
MIRT598550 | Isoc1 | isochorismatase domain containing 1 | 2 | 2 | ||||||||
MIRT599017 | Fgd4 | FYVE, RhoGEF and PH domain containing 4 | 2 | 2 | ||||||||
MIRT600307 | Tacc1 | transforming, acidic coiled-coil containing protein 1 | 2 | 2 | ||||||||
MIRT603647 | Otop1 | otopetrin 1 | 2 | 2 | ||||||||
MIRT605000 | Fam168b | family with sequence similarity 168, member B | 2 | 2 | ||||||||
MIRT606275 | Oxsm | 3-oxoacyl-ACP synthase, mitochondrial | 2 | 2 |
miRNA-Drug Associations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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