Major intrinsic protein is a member of the water-transporting aquaporins as well as the original member of the MIP family of channel proteins. The function of the fiber cell membrane protein encoded by this gene is undetermined, yet this protein is speculated to play a role in intracellular communication. The MIP protein is expressed in the ocular lens and is required for corre... See more...

Aliases for MIP Gene

Aliases for MIP Gene

  • Major Intrinsic Protein Of Lens Fiber 2 3 5
  • AQP0 2 3 4
  • MP26 2 3 4
  • Lens Fiber Major Intrinsic Protein 3 4
  • MIP26 3 4
  • LIM1 2 3
  • Aquaporin 0 3
  • Aquaporin-0 4
  • CTRCT15 3
  • MIP 5

External Ids for MIP Gene

Previous GeneCards Identifiers for MIP Gene

  • GC12P056780
  • GC12M057069
  • GC12M056561
  • GC12M055131
  • GC12M056843
  • GC12M053882

Summaries for MIP Gene

Entrez Gene Summary for MIP Gene

  • Major intrinsic protein is a member of the water-transporting aquaporins as well as the original member of the MIP family of channel proteins. The function of the fiber cell membrane protein encoded by this gene is undetermined, yet this protein is speculated to play a role in intracellular communication. The MIP protein is expressed in the ocular lens and is required for correct lens function. This gene has been mapped among aquaporins AQP2, AQP5, and AQP6, in a potential gene cluster at 12q13. [provided by RefSeq, Jul 2008]

GeneCards Summary for MIP Gene

MIP (Major Intrinsic Protein Of Lens Fiber) is a Protein Coding gene. Diseases associated with MIP include Cataract 15, Multiple Types and Cerulean Cataract. Among its related pathways are Aquaporin-mediated transport and Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds. Gene Ontology (GO) annotations related to this gene include transporter activity and structural constituent of eye lens. An important paralog of this gene is AQP2.

UniProtKB/Swiss-Prot Summary for MIP Gene

  • Water channel (PubMed:24120416). Channel activity is down-regulated by CALM when cytoplasmic Ca(2+) levels are increased. May be responsible for regulating the osmolarity of the lens. Interactions between homotetramers from adjoining membranes may stabilize cell junctions in the eye lens core (By similarity). Plays a role in cell-to-cell adhesion and facilitates gap junction coupling (PubMed:24120416).

Gene Wiki entry for MIP Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MIP Gene

Genomics for MIP Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for MIP Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12J056467 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 250.7 +0.3 342 2.8 BCLAF1 SP1 ZNF207 MYC SIX5 ZNF580 ATF2 KLF9 CEBPA POLR2A SPRYD4 MIP lnc-MIP-1 ANKRD52 ENSG00000257740 IKZF4 NAB2 R3HDM2 ENSG00000258199 ENSG00000285528
GH12J056454 Promoter 0.4 EPDnew 250.4 +14.5 14489 0.1 ZNF652 MIP GLS2 RBMS2 SMARCC2 TIMELESS lnc-MIP-1 SPRYD4 ENSG00000285528
GH12J055700 Enhancer 1.1 Ensembl ENCODE dbSUPER 5.6 +768.3 768265 1.4 ZNF600 NFIC ZIC2 ZBTB10 CEBPB ZNF639 ZEB1 MAX ZNF623 SP2 PAN2 ANKRD52 CD63 GDF11 ORMDL2 SARNP MIP lnc-CD63-4 HSALNG0091428 ITGA7
GH12J055498 Enhancer 0.8 ENCODE 4.6 +969.6 969558 2.5 CEBPA CHD2 FOXA2 KDM6A MAFF SMAD4 SAP130 ETV4 TAL1 RARA HSALNG0091418 OR6C70 MIP ENSG00000257303 OR6C68 OR6C4 ENSG00000258763
GH12J056447 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 0.4 +20.1 20099 2.3 MYC IKZF1 ZNF600 ZNF580 ZNF592 POLR2A NFIC ZIC2 YY1 MXD4 TIMELESS piR-38579-010 PRIM1 GLS2 DNAJC14 STAT2 APOF BAZ2A RBMS2 MIP
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MIP on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MIP

Top Transcription factor binding sites by QIAGEN in the MIP gene promoter:
  • AP-2alpha
  • AP-2alpha isoform 2
  • AP-2alpha isoform 3
  • AP-2alpha isoform 4
  • AP-2alphaA
  • ATF-2
  • c-Myc
  • Max
  • Sp1

Genomic Locations for MIP Gene

Latest Assembly
chr12:56,449,502-56,469,166
(GRCh38/hg38)
Size:
19,665 bases
Orientation:
Minus strand

Previous Assembly
chr12:56,843,286-56,848,441
(GRCh37/hg19 by Entrez Gene)
Size:
5,156 bases
Orientation:
Minus strand

chr12:56,843,286-56,862,950
(GRCh37/hg19 by Ensembl)
Size:
19,665 bases
Orientation:
Minus strand

Genomic View for MIP Gene

Genes around MIP on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for MIP Gene

Proteins for MIP Gene

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

    Protein Symbol:
    P30301-MIP_HUMAN
    Recommended name:
    Lens fiber major intrinsic protein
    Protein Accession:
    P30301
    Secondary Accessions:
    • Q17R41

    Protein attributes for MIP Gene

    Size:
    263 amino acids
    Molecular mass:
    28122 Da
    Quaternary structure:
    • Homotetramer (PubMed:24120416). Homooctamer formed by head-to-head interaction between homotetramers from adjoining membranes. Interacts with CALM; one CALM molecule interacts with the cytoplasmic domains of two aquaporins, leading to channel closure (By similarity). Interacts (via C-terminus) with BFSP1 (via C-terminus) in aged lens fiber cells (By similarity).

neXtProt entry for MIP Gene

Post-translational modifications for MIP Gene

  • Subject to partial proteolytic cleavage in the eye lens core. Partial proteolysis promotes interactions between tetramers from adjoining membranes (By similarity).
  • Fatty acylated at Met-1 and Lys-238. The acyl modifications, in decreasing order of ion abundance, are: oleoyl (C18:1) > palmitoyl (C16:0) > stearoyl (C18:0) > eicosenoyl (C20:1) > dihomo-gamma-linolenoyl (C20:3) > palmitoleoyl (C16:1) > eicosadienoyl (C20:2).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for MIP Gene

No data available for DME Specific Peptides for MIP Gene

Domains & Families for MIP Gene

Gene Families for MIP Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted membrane proteins

Protein Domains for MIP Gene

InterPro:
Blocks:
  • MIP family

Suggested Antigen Peptide Sequences for MIP Gene

GenScript: Design optimal peptide antigens:
  • MIP26 (MIP_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P30301

UniProtKB/Swiss-Prot:

MIP_HUMAN :
  • Aquaporins contain two tandem repeats each containing two membrane-spanning helices and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA). Each tandem repeat contains a loop and a short helix that enter and leave the lipid bilayer on the same side (By similarity).
  • Belongs to the MIP/aquaporin (TC 1.A.8) family.
Domain:
  • Aquaporins contain two tandem repeats each containing two membrane-spanning helices and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA). Each tandem repeat contains a loop and a short helix that enter and leave the lipid bilayer on the same side (By similarity).
Family:
  • Belongs to the MIP/aquaporin (TC 1.A.8) family.
genes like me logo Genes that share domains with MIP: view

Function for MIP Gene

Molecular function for MIP Gene

UniProtKB/Swiss-Prot Function:
Water channel (PubMed:24120416). Channel activity is down-regulated by CALM when cytoplasmic Ca(2+) levels are increased. May be responsible for regulating the osmolarity of the lens. Interactions between homotetramers from adjoining membranes may stabilize cell junctions in the eye lens core (By similarity). Plays a role in cell-to-cell adhesion and facilitates gap junction coupling (PubMed:24120416).
GENATLAS Biochemistry:
major intrinsic protein of lens fiber,1 (MP26),with water channel properties

Phenotypes From GWAS Catalog for MIP Gene

Gene Ontology (GO) - Molecular Function for MIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005212 structural constituent of eye lens IEA --
GO:0005515 protein binding IPI 32296183
GO:0005516 calmodulin binding ISS --
GO:0015250 water channel activity IEA,ISS --
GO:0015267 channel activity IEA --
genes like me logo Genes that share ontologies with MIP: view
genes like me logo Genes that share phenotypes with MIP: view

Human Phenotype Ontology for MIP Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for research

  • Taconic Biosciences Mouse Models for MIP

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MIP

No data available for Enzyme Numbers (IUBMB) , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for MIP Gene

Localization for MIP Gene

Subcellular locations from UniProtKB/Swiss-Prot for MIP Gene

Cell membrane. Multi-pass membrane protein. Cell junction, gap junction.

Subcellular locations from

COMPARTMENTS
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 MIP gene
Compartment Confidence
plasma membrane 5
endoplasmic reticulum 5
extracellular 2
cytoskeleton 2
nucleus 2
mitochondrion 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for MIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IDA 24120416
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS,ISS --
GO:0005921 gap junction IEA --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with MIP: view

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

Pathways & Interactions for MIP Gene

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

Pathways by source for MIP Gene

SIGNOR curated interactions for MIP Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for MIP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002088 lens development in camera-type eye IEA --
GO:0006833 water transport IEA,TAS --
GO:0007601 visual perception IEA --
GO:0045785 positive regulation of cell adhesion IDA 24120416
GO:0050896 response to stimulus IEA --
genes like me logo Genes that share ontologies with MIP: view

Drugs & Compounds for MIP Gene

(27) Drugs for MIP Gene - From: DrugBank, ClinicalTrials, DGIdb, IUPHAR, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
B-nonylglucoside Experimental Pharma Target 0
Hg<sup>2+</sup> Pharma Inhibitor 0
Respiratory System Agents Pharma 5136

(23) Additional Compounds for MIP Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with MIP: view

Transcripts for MIP Gene

mRNA/cDNA for MIP Gene

1 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MIP

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

No ASD Table

Relevant External Links for MIP Gene

GeneLoc Exon Structure for
MIP

Expression for MIP Gene

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MIP Gene

This gene is overexpressed in Testis (x10.6) and Liver (x7.6).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MIP

SOURCE GeneReport for Unigene cluster for MIP Gene:

Hs.574026

mRNA Expression by UniProt/SwissProt for MIP Gene:

P30301-MIP_HUMAN
Tissue specificity: Expressed in the cortex and nucleus of the retina lens (at protein level) (PubMed:30790544). Major component of lens fiber gap junctions (PubMed:24120416).

Evidence on tissue expression from TISSUES for MIP Gene

  • Eye(3.6)

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

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • nervous
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • cranial nerve
  • eye
  • head
General:
  • peripheral nervous system
genes like me logo Genes that share expression patterns with MIP: view

No data available for Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for MIP Gene

Orthologs for MIP Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for MIP Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia MIP 29 30
  • 99.87 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia MIP 29 30
  • 91.25 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia MIP 29 30
  • 90.87 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Mip 29
  • 89.86 (n)
Mouse
(Mus musculus)
Mammalia Mip 29 16 30
  • 89.1 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia MIP 30
  • 85 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia MIP 30
  • 76 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia MIP 30
  • 74 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia mip 29
  • 70.85 (n)
Zebrafish
(Danio rerio)
Actinopterygii mipa 29 30
  • 67.68 (n)
OneToMany
mipb 30
  • 66 (a)
OneToMany
Fruit Fly
(Drosophila melanogaster)
Insecta CG7777 31
  • 38 (a)
Thale Cress
(Arabidopsis thaliana)
eudicotyledons TIP2 29
  • 51.2 (n)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.7386 29
Species where no ortholog for MIP was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • 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)
  • Chicken (Gallus gallus)
  • 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)
  • 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 Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for MIP Gene

ENSEMBL:
Gene Tree for MIP (if available)
TreeFam:
Gene Tree for MIP (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MIP: view image
Alliance of Genome Resources:
Additional Orthologs for MIP

Paralogs for MIP Gene

(7) SIMAP similar genes for MIP Gene using alignment to 1 proteins:

  • MIP_HUMAN
genes like me logo Genes that share paralogs with MIP: view

Variants for MIP Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MIP Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
1012009 Uncertain Significance: Cataract 15, multiple types 56,453,683(-) T/G
NM_012064.4(MIP):c.433A>C (p.Ile145Leu)
MISSENSE
834061 Uncertain Significance: Microcornea; Congenital cataract; Microphthalmia; Nystagmus 56,453,602(-) GC/G
NM_012064.4(MIP):c.513del (p.His172fs)
FRAMESHIFT
880560 Uncertain Significance: Cataract 15, multiple types 56,449,785(-) A/G
NM_012064.4(MIP):c.*1495T>C
THREE_PRIME_UTR
880561 Uncertain Significance: Cataract 15, multiple types 56,450,018(-) G/C
NM_012064.4(MIP):c.*1262C>G
THREE_PRIME_UTR
880562 Benign: Cataract 15, multiple types 56,450,176(-) A/T
NM_012064.4(MIP):c.*1104T>A
THREE_PRIME_UTR

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for MIP Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

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

Variant ID Type Subtype PubMed ID
nsv1052713 CNV gain 25217958
nsv482992 CNV gain+loss 15286789

Variation tolerance for MIP Gene

Residual Variation Intolerance Score: 41% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.15; 51.61% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MIP Gene

Human Gene Mutation Database (HGMD)
MIP
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MIP
Leiden Open Variation Database (LOVD)
MIP

SNP Genotyping and Copy Number Assays for research

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

Disorders for MIP Gene

MalaCards: The human disease database

(27) MalaCards diseases for MIP Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

Disorder Aliases PubMed IDs
cataract 15, multiple types
  • ctrct15
cerulean cataract
  • cataract, congenital, blue dot type 1
early-onset non-syndromic cataract
early-onset sutural cataract
  • early-onset cataract with y-shaped suture opacities
early-onset posterior polar cataract
- elite association - COSMIC cancer census association via MalaCards
Search MIP in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

MIP_HUMAN
  • Cataract 15, multiple types (CTRCT15) [MIM:615274]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT15 includes polymorphic, progressive punctate lamellar, cortical, anterior and posterior polar, nonprogressive lamellar with sutural opacities, embryonic nuclear, and pulverulent cortical, among others. {ECO:0000269 PubMed:10802646, ECO:0000269 PubMed:11001937, ECO:0000269 PubMed:16564824, ECO:0000269 PubMed:17893667, ECO:0000269 PubMed:17960133, ECO:0000269 PubMed:20361015, ECO:0000269 PubMed:21245956, ECO:0000269 PubMed:23116563, ECO:0000269 PubMed:24120416, ECO:0000269 PubMed:25946197}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for MIP

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with MIP: view

No data available for Genatlas for MIP Gene

Publications for MIP Gene

  1. A novel mutation in major intrinsic protein of the lens gene (MIP) underlies autosomal dominant cataract in a Chinese family. (PMID: 17893667) Gu F … Ma X (Molecular vision 2007) 3 4 22 72
  2. Missense mutations in MIP underlie autosomal dominant 'polymorphic' and lamellar cataracts linked to 12q. (PMID: 10802646) Berry V … Bhattacharya S (Nature genetics 2000) 3 4 22 72
  3. Genomic cloning, complete nucleotide sequence, and structure of the human gene encoding the major intrinsic protein (MIP) of the lens. (PMID: 1840563) Pisano MM … Chepelinsky AB (Genomics 1991) 2 3 4 22
  4. An MIP/AQP0 mutation with impaired trafficking and function underlies an autosomal dominant congenital lamellar cataract. (PMID: 23116563) Senthil Kumar G … Santhiya ST (Experimental eye research 2013) 3 4 72
  5. A novel mutation in MIP associated with congenital nuclear cataract in a Chinese family. (PMID: 21245956) Wang KJ … Zhu SQ (Molecular vision 2011) 3 4 72

Products for MIP Gene

Sources for MIP Gene