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Aliases for MID1 Gene

Aliases for MID1 Gene

  • Midline 1 2 3 5
  • RING-Type E3 Ubiquitin Transferase Midline-1 3 4
  • Tripartite Motif-Containing Protein 18 3 4
  • Putative Transcription Factor XPRF 3 4
  • RING Finger Protein Midline-1 3 4
  • RING Finger Protein 59 3 4
  • Opitz/BBB Syndrome 2 3
  • TRIM18 3 4
  • RNF59 3 4
  • XPRF 3 4
  • FXY 3 4
  • Zinc Finger On X And Y, Mouse, Homolog Of 3
  • E3 Ubiquitin-Protein Ligase Midline-1 3
  • Tripartite Motif Protein TRIM18 3
  • Midline 1 RING Finger Protein 3
  • EC 4
  • BBBG1 3
  • GBBB1 3
  • MIDIN 3
  • ZNFXY 3
  • Midin 4
  • OGS1 3
  • OSX 3
  • OS 3

External Ids for MID1 Gene

Previous GeneCards Identifiers for MID1 Gene

  • GC0XM009445
  • GC0XM009230
  • GC0XM009760
  • GC0XM009827
  • GC0XM009825
  • GC0XM010225
  • GC0XM008245

Summaries for MID1 Gene

Entrez Gene Summary for MID1 Gene

  • The protein encoded by this gene is a member of the tripartite motif (TRIM) family, also known as the 'RING-B box-coiled coil' (RBCC) subgroup of RING finger proteins. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein forms homodimers which associate with microtubules in the cytoplasm. The protein is likely involved in the formation of multiprotein structures acting as anchor points to microtubules. Mutations in this gene have been associated with the X-linked form of Opitz syndrome, which is characterized by midline abnormalities such as cleft lip, laryngeal cleft, heart defects, hypospadias, and agenesis of the corpus callosum. This gene was also the first example of a gene subject to X inactivation in human while escaping it in mouse. Alternative promoter use, alternative splicing and alternative polyadenylation result in multiple transcript variants that have different tissue specificities. [provided by RefSeq, Dec 2016]

GeneCards Summary for MID1 Gene

MID1 (Midline 1) is a Protein Coding gene. Diseases associated with MID1 include Opitz Gbbb Syndrome, Type I and Opitz Gbbb Syndrome, Type Ii. Among its related pathways are Ubiquitin mediated proteolysis and Innate Immune System. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein heterodimerization activity. An important paralog of this gene is MID2.

UniProtKB/Swiss-Prot for MID1 Gene

  • Has E3 ubiquitin ligase activity towards IGBP1, promoting its monoubiquitination, which results in deprotection of the catalytic subunit of protein phosphatase PP2A, and its subsequent degradation by polyubiquitination.

Gene Wiki entry for MID1 Gene

Additional gene information for MID1 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MID1 Gene

Genomics for MID1 Gene

GeneHancer (GH) Regulatory Elements for MID1 Gene

Promoters and enhancers for MID1 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH0XJ010613 Promoter/Enhancer 2.3 EPDnew FANTOM5 Ensembl ENCODE 651.4 +493.6 493607 7.3 PKNOX1 SIN3A FEZF1 ZNF2 RAD21 RFX5 YY1 ZNF335 SCRT2 ZNF143 MID1 RNU6-800P PIR41928
GH0XJ011110 Promoter/Enhancer 2.1 EPDnew FANTOM5 Ensembl ENCODE 650.7 -1.2 -1245 4.2 PKNOX1 SMAD1 ATF1 ARNT ARID4B SIN3A ZNF48 YY1 POLR2B ELK1 HCCS MID1 ENSG00000234129 ENSG00000207151 GC0XM011116
GH0XJ010832 Promoter/Enhancer 1.7 EPDnew FANTOM5 Ensembl ENCODE 650.1 +277.7 277691 1.4 POLR2A HMBOX1 REST MID1 PIR41928 ENSG00000234129
GH0XJ010576 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE 650 +531.4 531409 6.8 HDAC1 ATF1 SIN3A FEZF1 RFX5 YY1 TCF12 EGR1 FOS ATF7 MID1 GC0XP010582 RNU6-800P GC0XM010498
GH0XJ010588 Promoter/Enhancer 1.1 EPDnew ENCODE 650 +521.5 521534 2.1 PKNOX1 FOXA2 ARNT ELF4 MAX RAD21 CTBP1 GATA3 TCF7L2 MID1 RNU6-800P PIR41928
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around MID1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the MID1 gene promoter:
  • c-Jun
  • ATF-2
  • AP-1
  • C/EBPalpha

Genomic Locations for MID1 Gene

Genomic Locations for MID1 Gene
665,868 bases
Minus strand
438,460 bases
Minus strand

Genomic View for MID1 Gene

Genes around MID1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MID1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MID1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MID1 Gene

Proteins for MID1 Gene

  • Protein details for MID1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    E3 ubiquitin-protein ligase Midline-1
    Protein Accession:
    Secondary Accessions:
    • B2RCG2
    • O75361
    • Q9BZX5

    Protein attributes for MID1 Gene

    667 amino acids
    Molecular mass:
    75251 Da
    Quaternary structure:
    • Homodimer or heterodimer with MID2. Interacts with IGBP1.

    Three dimensional structures from OCA and Proteopedia for MID1 Gene

    Alternative splice isoforms for MID1 Gene


neXtProt entry for MID1 Gene

Post-translational modifications for MID1 Gene

No data available for DME Specific Peptides for MID1 Gene

Domains & Families for MID1 Gene

Gene Families for MID1 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins
  • Predicted membrane proteins

Suggested Antigen Peptide Sequences for MID1 Gene

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the TRIM/RBCC family.
  • Belongs to the TRIM/RBCC family.
genes like me logo Genes that share domains with MID1: view

Function for MID1 Gene

Molecular function for MID1 Gene

UniProtKB/Swiss-Prot Function:
Has E3 ubiquitin ligase activity towards IGBP1, promoting its monoubiquitination, which results in deprotection of the catalytic subunit of protein phosphatase PP2A, and its subsequent degradation by polyubiquitination.
UniProtKB/Swiss-Prot CatalyticActivity:
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.
UniProtKB/Swiss-Prot Induction:
A retroviral element acts as an alternative tissue-specific promoter for this gene. The LTR of an HERV-E element enhances the expression in placenta and embryonic kidney.
GENATLAS Biochemistry:
midline 1,transcriptional regulator,midin,ubiquitously expressed,with alternatively spliced isoforms,forming large protein complexes,associating with microtubules and influencing microtubule dynamics throughout the cell cycle,colocalizing with cytoplasmic fibres in interphase and with the mitotic spindle and midbodies during mitosis and cytokinesis,involved in body axis patterning and cell transformation,homologous to Xenopus XNF7,B box family

Enzyme Numbers (IUBMB) for MID1 Gene

Phenotypes From GWAS Catalog for MID1 Gene

Gene Ontology (GO) - Molecular Function for MID1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 19549727
GO:0008017 microtubule binding IMP 11806752
GO:0008270 zinc ion binding IEA --
GO:0016740 transferase activity IEA --
GO:0031625 ubiquitin protein ligase binding IPI 17438131
genes like me logo Genes that share ontologies with MID1: view
genes like me logo Genes that share phenotypes with MID1: view

Human Phenotype Ontology for MID1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for MID1 Gene

MGI Knock Outs for MID1:

Animal Model Products

Clone Products

No data available for Transcription Factor Targets and HOMER Transcription for MID1 Gene

Localization for MID1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MID1 Gene

Cytoplasm. Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, spindle. Note=Microtubule-associated. It is associated with microtubules throughout the cell cycle, co-localizing with cytoplasmic fibers in interphase and with the mitotic spindle and midbodies during mitosis and cytokinesis.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MID1 gene
Compartment Confidence
cytoskeleton 5
cytosol 5
extracellular 1

Gene Ontology (GO) - Cellular Components for MID1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular IEA --
GO:0005737 cytoplasm IEA --
GO:0005819 spindle IEA --
GO:0005829 cytosol TAS --
GO:0005856 cytoskeleton IEA --
genes like me logo Genes that share ontologies with MID1: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for MID1 Gene

Pathways & Interactions for MID1 Gene

genes like me logo Genes that share pathways with MID1: view

Pathways by source for MID1 Gene

Gene Ontology (GO) - Biological Process for MID1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000226 microtubule cytoskeleton organization TAS 10077590
GO:0007026 negative regulation of microtubule depolymerization IEA --
GO:0007389 pattern specification process TAS 9354791
GO:0032874 positive regulation of stress-activated MAPK cascade IMP 17438131
GO:0035372 protein localization to microtubule IMP 11806752
genes like me logo Genes that share ontologies with MID1: view

No data available for SIGNOR curated interactions for MID1 Gene

Drugs & Compounds for MID1 Gene

(3) Drugs for MID1 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Phosphoric acid Approved Pharma 0
Adenosine monophosphate Approved, Investigational Nutra 0
ATP Investigational Nutra Agonist, Activator, Full agonist, Antagonist, Potentiation, Pore Blocker 0

(1) Additional Compounds for MID1 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • [(ho)2P(O)OP(O)(OH)2]
  • Acide diphosphorique
  • Diphosphorsaeure
  • H4P2O7
  • PYROphosphATE
genes like me logo Genes that share compounds with MID1: view

Transcripts for MID1 Gene

Unigene Clusters for MID1 Gene

Midline 1 (Opitz/BBB syndrome):
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for MID1 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b · 4c ^ 5a · 5b · 5c ^ 6a · 6b · 6c · 6d · 6e ^ 7 ^ 8 ^ 9a · 9b · 9c · 9d ^ 10a · 10b ^ 11 ^ 12 ^ 13 ^ 14a ·
SP1: - - - - - - - - - - - - - - - -
SP2: - - - - - - - - -
SP3: - -
SP4: - - - - - - - - - - - -
SP7: - - - - - - - - - - - - - - -
SP8: - - - - - - - - - - - - - -
SP9: - - - - - - - - - - -
SP12: - - - - - - - - - - - - -
SP13: - -
SP14: - - - - - - - - - - - - - -
SP15: - - - -
SP16: - - - - - - - -
SP17: - - - - -
SP18: - - - - - - -
SP21: -
SP23: -
SP24: - -
SP26: -
SP27: - -

ExUns: 14b · 14c ^ 15a · 15b ^ 16a · 16b ^ 17a · 17b ^ 18 ^ 19a · 19b
SP1: - - - - -
SP2: - - - - -
SP3: - - - - -
SP4: - - -
SP5: - - - -
SP6: - - -
SP7: - - -
SP8: - - -
SP11: - -

Relevant External Links for MID1 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for MID1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MID1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for MID1 Gene

This gene is overexpressed in Breast (19.3), Lung (9.2), Fetal Brain (8.8), and Urinary Bladder (6.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for MID1 Gene

Protein tissue co-expression partners for MID1 Gene

NURSA nuclear receptor signaling pathways regulating expression of MID1 Gene:


SOURCE GeneReport for Unigene cluster for MID1 Gene:


mRNA Expression by UniProt/SwissProt for MID1 Gene:

Tissue specificity: In the fetus, highest expression found in kidney, followed by brain and lung. Expressed at low levels in fetal liver. In the adult, most abundant in heart, placenta and brain.

Evidence on tissue expression from TISSUES for MID1 Gene

  • Nervous system(4.7)
  • Liver(4.1)
  • Skin(4.1)
  • Pancreas(3.8)

Phenotype-based relationships between genes and organs from Gene ORGANizer for MID1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeleton
  • urinary
Head and neck:
  • brain
  • epiglottis
  • eye
  • eyelid
  • face
  • forehead
  • head
  • lip
  • mouth
  • nose
  • pharynx
  • skull
  • bronchus
  • esophagus
  • lung
  • trachea
  • intestine
  • large intestine
  • stomach
  • anus
  • penis
  • rectum
  • testicle
  • urethra
  • hair
  • skin
genes like me logo Genes that share expression patterns with MID1: view

No data available for mRNA differential expression in normal tissues for MID1 Gene

Orthologs for MID1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for MID1 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia MID1 34
  • 100 (a)
(Monodelphis domestica)
Mammalia MID1 34
  • 97 (a)
(Ornithorhynchus anatinus)
Mammalia MID1 34
  • 96 (a)
(Canis familiaris)
Mammalia MID1 34 33
  • 94 (n)
(Bos Taurus)
Mammalia MID1 34 33
  • 92.2 (n)
(Rattus norvegicus)
Mammalia Mid1 33
  • 92.05 (n)
(Mus musculus)
Mammalia Gm21857 34
  • 90 (a)
Mid1 16 34 33
  • 88.71 (n)
(Gallus gallus)
Aves MID1 34 33
  • 84.43 (n)
(Anolis carolinensis)
Reptilia MID1 34
  • 96 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia mid1 33
  • 79.68 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.13388 33
(Danio rerio)
Actinopterygii mid1 34 33
  • 73.97 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 41 (a)
Species where no ortholog for MID1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for MID1 Gene

Gene Tree for MID1 (if available)
Gene Tree for MID1 (if available)
Evolutionary constrained regions (ECRs) for MID1: view image

Paralogs for MID1 Gene

Paralogs for MID1 Gene

(6) SIMAP similar genes for MID1 Gene using alignment to 3 proteins:

  • C9J453_HUMAN
genes like me logo Genes that share paralogs with MID1: view

Variants for MID1 Gene

Sequence variations from dbSNP and Humsavar for MID1 Gene

SNP ID Clin Chr 0X pos Variation AA Info Type
rs104894865 pathogenic, Opitz-Frias syndrome 10,567,205(-) C/A/G/T coding_sequence_variant, missense_variant, stop_gained
rs104894866 pathogenic, Opitz-Frias syndrome, Opitz GBBB syndrome 1 (GBBB1) [MIM:300000] 10,482,609(-) A/G coding_sequence_variant, genic_downstream_transcript_variant, missense_variant
rs144641429 uncertain-significance, benign, not provided, not specified 11,112,065(-) G/A upstream_transcript_variant
rs28934611 pathogenic, Opitz-Frias syndrome, Opitz GBBB syndrome 1 (GBBB1) [MIM:300000] 10,449,495(-) A/G coding_sequence_variant, genic_downstream_transcript_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for MID1 Gene

Variant ID Type Subtype PubMed ID
nsv819623 CNV gain 19587683
nsv478619 CNV novel sequence insertion 20440878
nsv477092 CNV novel sequence insertion 20440878
nsv475875 CNV novel sequence insertion 20440878
nsv1153653 CNV duplication 26484159
nsv1119330 CNV duplication 24896259
nsv1078667 CNV duplication 25765185
esv3573571 CNV loss 25503493
esv3573570 CNV loss 25503493
esv3573569 CNV loss 25503493
esv3573568 CNV loss 25503493
esv3573567 CNV loss 25503493
esv3558615 CNV deletion 23714750
esv3558613 CNV deletion 23714750
esv3558612 CNV deletion 23714750
esv2670028 CNV deletion 23128226
esv22291 CNV loss 19812545
dgv500n21 CNV gain 19592680

Variation tolerance for MID1 Gene

Residual Variation Intolerance Score: 5.92% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.78; 33.69% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MID1 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MID1 Gene

Disorders for MID1 Gene

MalaCards: The human disease database

(16) MalaCards diseases for MID1 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
opitz gbbb syndrome, type i
  • hypertelorism with esophageal abnormality and hypospadias
opitz gbbb syndrome, type ii
  • gbbb2
opitz-gbbb syndrome
  • hypertelorism with esophageal abnormality and hypospadias
tracheoesophageal fistula
  • tracheoesophageal fistula with or without esophageal atresia
x-linked opitz g/bbb syndrome
- elite association - COSMIC cancer census association via MalaCards
Search MID1 in MalaCards View complete list of genes associated with diseases


  • Opitz GBBB syndrome 1 (GBBB1) [MIM:300000]: A congenital midline malformation syndrome characterized by hypertelorism, genital-urinary defects such as hypospadias in males and splayed labia in females, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and congenital heart defects. {ECO:0000269 PubMed:11030761, ECO:0000269 PubMed:15558842, ECO:0000269 PubMed:9354791, ECO:0000269 PubMed:9718340}. Note=The disease is caused by mutations affecting the gene represented in this entry. MID1 mutations produce proteins with a decreased affinity for microtubules.

Genatlas disease for MID1 Gene

midline 1,Opitz-G syndrome 1 including the BBB syndrome,characterized by dysplasia of the corpus callosum hypertelorism,cleft lip/palate,dysphagia and laryngotracheo-esophageal fistulas,hoarse cry,hypospadias,imperforate anus,developmental delay and other anomalies

Additional Disease Information for MID1

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with MID1: view

Publications for MID1 Gene

  1. Opitz G/BBB syndrome, a defect of midline development, is due to mutations in a new RING finger gene on Xp22. (PMID: 9354791) Quaderi NA … Ballabio A (Nature genetics 1997) 2 3 4 22 58
  2. Solution structure of the RBCC/TRIM B-box1 domain of human MID1: B-box with a RING. (PMID: 16529770) Massiah MA … Cox TC (Journal of molecular biology 2006) 3 4 22 58
  3. MID1 and MID2 homo- and heterodimerise to tether the rapamycin-sensitive PP2A regulatory subunit, alpha 4, to microtubules: implications for the clinical variability of X-linked Opitz GBBB syndrome and other developmental disorders. (PMID: 11806752) Short KM … Cox TC (BMC cell biology 2002) 3 4 22 58
  4. MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation. (PMID: 11685209) Trockenbacher A … Schweiger S (Nature genetics 2001) 3 4 22 58
  5. The Opitz syndrome gene product, MID1, associates with microtubules. (PMID: 10077590) Schweiger S … Ropers HH (Proceedings of the National Academy of Sciences of the United States of America 1999) 3 4 22 58

Products for MID1 Gene

Sources for MID1 Gene

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