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Aliases for MCOLN3 Gene

Aliases for MCOLN3 Gene

  • Mucolipin 3 2 3 5
  • Transient Receptor Potential Channel Mucolipin 3 3 4
  • TRPML3 3 4
  • Mucolipin-3 3
  • TRP-ML3 3

External Ids for MCOLN3 Gene

Previous GeneCards Identifiers for MCOLN3 Gene

  • GC01M085879
  • GC01M084622
  • GC01M084772
  • GC01M084907
  • GC01M084906
  • GC01M085195
  • GC01M085483
  • GC01M083593

Summaries for MCOLN3 Gene

Entrez Gene Summary for MCOLN3 Gene

  • This gene encodes one of members of the mucolipin cation channel proteins. Mutation studies of the highly similar protein in mice have shown that the protein is found in cochlea hair cells, and mutant mice show early-onset hearing loss and balance problems. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

GeneCards Summary for MCOLN3 Gene

MCOLN3 (Mucolipin 3) is a Protein Coding gene. Among its related pathways are TRP channels and Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds. An important paralog of this gene is MCOLN1.

UniProtKB/Swiss-Prot for MCOLN3 Gene

  • Nonselective ligand-gated cation channel probably playing a role in the regulation of membrane trafficking events. Acts as Ca(2+)-permeable cation channel with inwardly rectifying activity (PubMed:18369318, PubMed:19497048, PubMed:19522758, PubMed:19885840, PubMed:29106414). Mediates release of Ca(2+) from endosomes to the cytoplasm, contributes to endosomal acidification and is involved in the regulation of membrane trafficking and fusion in the endosomal pathway (PubMed:21245134). Does not seem to act as mechanosensory transduction channel in inner ear sensory hair cells. Proposed to play a critical role at the cochlear stereocilia ankle-link region during hair-bundle growth (By similarity). Involved in the regulation of autophagy (PubMed:19522758). Through association with GABARAPL2 may be involved in autophagosome formation possibly providing Ca(2+) for the fusion process (By similarity). Through a possible and probably tissue-specific heteromerization with MCOLN1 may be at least in part involved in many lysosome-dependent cellular events (PubMed:19885840). Possible heteromeric ion channel assemblies with TRPV5 show pharmacological similarity with TRPML3 (PubMed:23469151).

Gene Wiki entry for MCOLN3 Gene

Additional gene information for MCOLN3 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MCOLN3 Gene

Genomics for MCOLN3 Gene

GeneHancer (GH) Regulatory Elements for MCOLN3 Gene

Promoters and enhancers for MCOLN3 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
GH01J085047 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 670 0.0 -47 3.1 FEZF1 GLI4 ZNF2 ZNF121 GLIS2 ZNF213 KLF7 SP3 REST TSHZ1 MCOLN3 ENSG00000271576 MCOLN2 ZNHIT6 WDR63 MIR4423
GH01J084994 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE 11.4 +53.1 53054 3.5 PKNOX1 BMI1 BATF IRF4 ZNF335 GLIS2 ZNF143 ZNF207 ATF7 KLF7 MCOLN2 WDR63 MCOLN3 LPAR3
GH01J084959 Enhancer 0.7 ENCODE 29 +88.5 88488 1.1 PKNOX1 JUN MAX SIN3A CEBPG RFX5 TEAD3 CTBP1 GATA3 RCOR1 MCOLN2 MCOLN3 LPAR3
GH01J084968 Enhancer 0.7 ENCODE 17.2 +79.2 79198 1.8 SMAD1 PAX8 EBF1 BATF KLF5 IRF4 RELA EED ATF7 ETV6 MCOLN2 MCOLN3 WDR63 LPAR3
GH01J084913 Enhancer 0.8 ENCODE 10.1 +135.1 135105 1 INSM2 MZF1 FEZF1 KLF14 ZNF2 ZNF335 ZNF366 EGR2 ZNF362 CEBPB LPAR3 MCOLN3 MCOLN2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MCOLN3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the MCOLN3 gene promoter:
  • Pax-2b
  • Pax-2a
  • Pax-2
  • Sox5
  • RFX1
  • AP-2gamma
  • LCR-F1
  • POU6F1 (c2)
  • Bach2

Genomic Locations for MCOLN3 Gene

Genomic Locations for MCOLN3 Gene
chr1:85,018,082-85,048,902
(GRCh38/hg38)
Size:
30,821 bases
Orientation:
Minus strand
chr1:85,483,765-85,514,182
(GRCh37/hg19)
Size:
30,418 bases
Orientation:
Minus strand

Genomic View for MCOLN3 Gene

Genes around MCOLN3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MCOLN3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MCOLN3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MCOLN3 Gene

Proteins for MCOLN3 Gene

  • Protein details for MCOLN3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8TDD5-MCLN3_HUMAN
    Recommended name:
    Mucolipin-3
    Protein Accession:
    Q8TDD5
    Secondary Accessions:
    • Q5T4H5
    • Q5T4H6
    • Q9NV09

    Protein attributes for MCOLN3 Gene

    Size:
    553 amino acids
    Molecular mass:
    64248 Da
    Quaternary structure:
    • Homotetramer (PubMed:29106414). Can heterooligomerize with MCOLN1; heteromeric assemblies have different channel properties as compared to the respective homooligomers and may be tissue-specific (PubMed:19885840). May heterooligomerize with TRPV5 to form a functional distinct ion channel (PubMed:23469151). Interacts with GABARAPL2 (By similarity).

    Three dimensional structures from OCA and Proteopedia for MCOLN3 Gene

    Alternative splice isoforms for MCOLN3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MCOLN3 Gene

Post-translational modifications for MCOLN3 Gene

No data available for DME Specific Peptides for MCOLN3 Gene

Domains & Families for MCOLN3 Gene

Gene Families for MCOLN3 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Predicted membrane proteins
  • Transporters
  • Voltage-gated ion channels

Protein Domains for MCOLN3 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for MCOLN3 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q8TDD5

UniProtKB/Swiss-Prot:

MCLN3_HUMAN :
  • The most N-terminal extracellular/lumenal domain (referred to as I-II linker or polycystin-mucolipin domain) contributes to a structure with a four-fold rotational symmetry in a tetrameric assembly; the structure contains a central highly electronegative pore with a 14 A diameter. The pore is critical for Ca(2+) and pH regulation. The protruding structure formed by the I-II linkers may contain all the interaction sites with lipids and proteins in the endolysosomal lumen.
  • Belongs to the transient receptor (TC 1.A.4) family. Polycystin subfamily. MCOLN3 sub-subfamily.
Domain:
  • The most N-terminal extracellular/lumenal domain (referred to as I-II linker or polycystin-mucolipin domain) contributes to a structure with a four-fold rotational symmetry in a tetrameric assembly; the structure contains a central highly electronegative pore with a 14 A diameter. The pore is critical for Ca(2+) and pH regulation. The protruding structure formed by the I-II linkers may contain all the interaction sites with lipids and proteins in the endolysosomal lumen.
Family:
  • Belongs to the transient receptor (TC 1.A.4) family. Polycystin subfamily. MCOLN3 sub-subfamily.
genes like me logo Genes that share domains with MCOLN3: view

Function for MCOLN3 Gene

Molecular function for MCOLN3 Gene

UniProtKB/Swiss-Prot Function:
Nonselective ligand-gated cation channel probably playing a role in the regulation of membrane trafficking events. Acts as Ca(2+)-permeable cation channel with inwardly rectifying activity (PubMed:18369318, PubMed:19497048, PubMed:19522758, PubMed:19885840, PubMed:29106414). Mediates release of Ca(2+) from endosomes to the cytoplasm, contributes to endosomal acidification and is involved in the regulation of membrane trafficking and fusion in the endosomal pathway (PubMed:21245134). Does not seem to act as mechanosensory transduction channel in inner ear sensory hair cells. Proposed to play a critical role at the cochlear stereocilia ankle-link region during hair-bundle growth (By similarity). Involved in the regulation of autophagy (PubMed:19522758). Through association with GABARAPL2 may be involved in autophagosome formation possibly providing Ca(2+) for the fusion process (By similarity). Through a possible and probably tissue-specific heteromerization with MCOLN1 may be at least in part involved in many lysosome-dependent cellular events (PubMed:19885840). Possible heteromeric ion channel assemblies with TRPV5 show pharmacological similarity with TRPML3 (PubMed:23469151).
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by lumenal H(+) and Na(+) (PubMed:18369318, PubMed:29106414). The channel pore shows dynamic behavior and undergoes spontaneous, Ca(2+)-dependent modulation when conducting Ca(2+) (PubMed:20378547).

Phenotypes From GWAS Catalog for MCOLN3 Gene

Gene Ontology (GO) - Molecular Function for MCOLN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005262 calcium channel activity TAS --
GO:0008289 lipid binding IEA --
GO:0072345 NAADP-sensitive calcium-release channel activity IBA --
genes like me logo Genes that share ontologies with MCOLN3: view
genes like me logo Genes that share phenotypes with MCOLN3: view

Animal Models for MCOLN3 Gene

MGI Knock Outs for MCOLN3:

Animal Model Products

  • Taconic Biosciences Mouse Models for MCOLN3

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MCOLN3

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MCOLN3 Gene

Localization for MCOLN3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MCOLN3 Gene

Cell membrane; Multi-pass membrane protein. Early endosome membrane; Multi-pass membrane protein. Late endosome membrane; Multi-pass membrane protein. Lysosome membrane; Multi-pass membrane protein. Cytoplasmic vesicle, autophagosome membrane. Note=Recycles between the plasma membrane and intracellular compartments by a dynamin-dependent endocytic pathway (PubMed:19522758). Under normal conditions, only a very minor proportion is present at the cell membrane (PubMed:19522758). In the cochlea located at the base of stereocilia near the position of the ankle links (By similarity). {ECO:0000250 UniProtKB:Q8R4F0, ECO:0000269 PubMed:19522758}.

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 MCOLN3 gene
Compartment Confidence
plasma membrane 5
lysosome 4
endosome 4
nucleus 2
cytosol 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nucleoli (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MCOLN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000421 autophagosome membrane IEA --
GO:0005737 cytoplasm IEA --
GO:0005764 lysosome IEA --
GO:0005765 lysosomal membrane IEA --
GO:0005768 endosome IEA --
genes like me logo Genes that share ontologies with MCOLN3: view

Pathways & Interactions for MCOLN3 Gene

genes like me logo Genes that share pathways with MCOLN3: view

Pathways by source for MCOLN3 Gene

Interacting Proteins for MCOLN3 Gene

Gene Ontology (GO) - Biological Process for MCOLN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0007626 locomotory behavior IEA --
GO:0042491 inner ear auditory receptor cell differentiation IEA --
GO:0070588 calcium ion transmembrane transport TAS --
genes like me logo Genes that share ontologies with MCOLN3: view

No data available for SIGNOR curated interactions for MCOLN3 Gene

Drugs & Compounds for MCOLN3 Gene

(7) Drugs for MCOLN3 Gene - From: DGIdb, IUPHAR, and Tocris

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
SF-11 Pharma 0
SF-21 Pharma 0
SN-1 Pharma 0
SN-2 Pharma 0
Gd<sup>3+</sup> Pharma Channel blocker, Pore Blocker, Antagonist, Activator 0

(1) Additional Compounds for MCOLN3 Gene - From: Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
MK6-83
1062271-24-2

(3) Tocris Compounds for MCOLN3 Gene

Compound Action Cas Number
MK6-83 TRPML channel activator 1062271-24-2
ML SA1 Activator of TRPML channels 332382-54-4
SN 2 Selective TRPML3 channel activator 823218-99-1
genes like me logo Genes that share compounds with MCOLN3: view

Transcripts for MCOLN3 Gene

Unigene Clusters for MCOLN3 Gene

Mucolipin 3:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MCOLN3

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for MCOLN3 Gene

ExUns: 1 ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7a · 7b · 7c ^ 8 ^ 9a · 9b ^ 10 ^ 11 ^ 12
SP1:
SP2: - -
SP3: -
SP4:
SP5:

Relevant External Links for MCOLN3 Gene

GeneLoc Exon Structure for
MCOLN3
ECgene alternative splicing isoforms for
MCOLN3

Expression for MCOLN3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MCOLN3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MCOLN3 Gene

This gene is overexpressed in Adrenal Gland (x10.6) and Pituitary (x6.0).

Protein differential expression in normal tissues from HIPED for MCOLN3 Gene

This gene is overexpressed in Plasma (67.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for MCOLN3 Gene



Protein tissue co-expression partners for MCOLN3 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of MCOLN3 Gene:

MCOLN3

SOURCE GeneReport for Unigene cluster for MCOLN3 Gene:

Hs.535239
genes like me logo Genes that share expression patterns with MCOLN3: view

No data available for mRNA Expression by UniProt/SwissProt , Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for MCOLN3 Gene

Orthologs for MCOLN3 Gene

This gene was present in the common ancestor of animals.

Orthologs for MCOLN3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MCOLN3 34 33
  • 99.76 (n)
OneToOne
dog
(Canis familiaris)
Mammalia MCOLN3 34 33
  • 91.74 (n)
OneToOne
cow
(Bos Taurus)
Mammalia MCOLN3 34 33
  • 90.42 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 34
  • 85 (a)
OneToMany
-- 34
  • 79 (a)
OneToMany
mouse
(Mus musculus)
Mammalia Mcoln3 16 34 33
  • 84.87 (n)
rat
(Rattus norvegicus)
Mammalia Mcoln3 33
  • 84.33 (n)
oppossum
(Monodelphis domestica)
Mammalia MCOLN3 34
  • 84 (a)
OneToOne
chicken
(Gallus gallus)
Aves MCOLN3 34 33
  • 76.23 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MCOLN3 34
  • 84 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia mcoln3 33
  • 72.25 (n)
zebrafish
(Danio rerio)
Actinopterygii LOC100001113 33
  • 62.24 (n)
MCOLN3 (1 of 2) 34
  • 58 (a)
OneToMany
mcoln3a 34
  • 56 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta trpml 34 33
  • 50.42 (n)
ManyToMany
CG8743 35
  • 41 (a)
CG42638 34
  • 35 (a)
ManyToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP007710 33
  • 50.33 (n)
worm
(Caenorhabditis elegans)
Secernentea cup-5 34 35 33
  • 48.74 (n)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 41 (a)
OneToMany
Cin.10964 33
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.10964 33
Species where no ortholog for MCOLN3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • 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)

Evolution for MCOLN3 Gene

ENSEMBL:
Gene Tree for MCOLN3 (if available)
TreeFam:
Gene Tree for MCOLN3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MCOLN3: view image

Paralogs for MCOLN3 Gene

Paralogs for MCOLN3 Gene

(2) SIMAP similar genes for MCOLN3 Gene using alignment to 4 proteins:

  • MCLN3_HUMAN
  • B1ANB7_HUMAN
  • Q6P9H1_HUMAN
  • S4R386_HUMAN
genes like me logo Genes that share paralogs with MCOLN3: view

Variants for MCOLN3 Gene

Sequence variations from dbSNP and Humsavar for MCOLN3 Gene

SNP ID Clin Chr 01 pos Variation AA Info Type
rs1000164194 -- 85,025,385(-) GGGG/GGG intron_variant, non_coding_transcript_variant
rs1000225711 -- 85,035,321(-) C/T intron_variant
rs1000271034 -- 85,017,618(-) A/G downstream_transcript_variant
rs1000460804 -- 85,042,687(-) T/C intron_variant
rs1000572675 -- 85,036,953(-) A/G intron_variant

Structural Variations from Database of Genomic Variants (DGV) for MCOLN3 Gene

Variant ID Type Subtype PubMed ID
nsv462383 CNV gain 19166990
nsv470724 CNV gain 18288195
nsv546700 CNV gain 21841781
nsv830448 CNV loss 17160897
nsv947434 CNV duplication 23825009

Variation tolerance for MCOLN3 Gene

Residual Variation Intolerance Score: 48.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.49; 29.00% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MCOLN3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
MCOLN3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MCOLN3 Gene

Disorders for MCOLN3 Gene

Additional Disease Information for MCOLN3

No disorders were found for MCOLN3 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for MCOLN3 Gene

Publications for MCOLN3 Gene

  1. Functional multimerization of mucolipin channel proteins. (PMID: 19885840) Curcio-Morelli C … Slaugenhaupt SA (Journal of cellular physiology 2010) 3 4 22 58
  2. The calcium channel mucolipin-3 is a novel regulator of trafficking along the endosomal pathway. (PMID: 19497048) Martina JA … Puertollano R (Traffic (Copenhagen, Denmark) 2009) 3 4 22 58
  3. A novel ion channel formed by interaction of TRPML3 with TRPV5. (PMID: 23469151) Guo Z … Heller S (PloS one 2013) 3 4 58
  4. Properties of the TRPML3 channel pore and its stable expansion by the Varitint-Waddler-causing mutation. (PMID: 20378547) Kim HJ … Muallem S (The Journal of biological chemistry 2010) 3 4 58
  5. The Ca(2+) channel TRPML3 regulates membrane trafficking and autophagy. (PMID: 19522758) Kim HJ … Muallem S (Traffic (Copenhagen, Denmark) 2009) 3 4 58

Products for MCOLN3 Gene

Sources for MCOLN3 Gene

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