The protein encoded by this gene is an integral membrane protein localized to the endoplasmic reticulum (ER). The encoded protein contains many tetratricopeptide repeats, sequences known for being involved in protein-protein interactions. This protein binds both the calcium uptake pump SERCA2B and the carbohydrate-binding chaperone calnexin, and it appears to play a role in cal... See more...

Aliases for TMTC2 Gene

Aliases for TMTC2 Gene

  • Transmembrane O-Mannosyltransferase Targeting Cadherins 2 2 3 5
  • Transmembrane And Tetratricopeptide Repeat Containing 2 2 3
  • Transmembrane And TPR Repeat-Containing Protein 2 3 4
  • Protein O-Mannosyl-Transferase TMTC2 3 4
  • EC 2.4.1.109 4
  • IBDBP1 3

External Ids for TMTC2 Gene

Previous GeneCards Identifiers for TMTC2 Gene

  • GC12P081584
  • GC12P083080
  • GC12P080139

Summaries for TMTC2 Gene

Entrez Gene Summary for TMTC2 Gene

  • The protein encoded by this gene is an integral membrane protein localized to the endoplasmic reticulum (ER). The encoded protein contains many tetratricopeptide repeats, sequences known for being involved in protein-protein interactions. This protein binds both the calcium uptake pump SERCA2B and the carbohydrate-binding chaperone calnexin, and it appears to play a role in calcium homeostasis in the ER. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

GeneCards Summary for TMTC2 Gene

TMTC2 (Transmembrane O-Mannosyltransferase Targeting Cadherins 2) is a Protein Coding gene. Diseases associated with TMTC2 include Auditory Neuropathy, Autosomal Dominant, 1 and Open-Angle Glaucoma. Gene Ontology (GO) annotations related to this gene include identical protein binding. An important paralog of this gene is TMTC1.

UniProtKB/Swiss-Prot Summary for TMTC2 Gene

  • Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. The 4 members of the TMTC family are O-mannosyl-transferases dedicated primarily to the cadherin superfamily, each member seems to have a distinct role in decorating the cadherin domains with O-linked mannose glycans at specific regions. Also acts as O-mannosyl-transferase on other proteins such as PDIA3.

Gene Wiki entry for TMTC2 Gene

Additional gene information for TMTC2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TMTC2 Gene

Genomics for TMTC2 Gene

GeneHancer (GH) Regulatory Elements for TMTC2 Gene

Promoters and enhancers for TMTC2 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
GH12J082685 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 510.2 +0.7 721 5.6 ZNF217 EP300 CTCF SIN3A NRF1 POLR2G ZNF10 POLR2A CLOCK ZNF423 TMTC2 ENSG00000286043 piR-31016
GH12J082664 Enhancer 0.4 Ensembl 18 -21.8 -21779 2.2 ZNF316 MAFF SRF MAFK FOS TMTC2 ENSG00000286043 piR-38351-107
GH12J082883 Enhancer 0.6 Ensembl ENCODE dbSUPER 13.1 +196.7 196666 0.3 ZBTB44 TMTC2 RF00017-1195 piR-30876-029
GH12J082682 Enhancer 0.8 Ensembl ENCODE 9.2 -3.8 -3779 1.8 ZNF217 TCF12 CUX1 CTBP1 MXI1 CEBPG CEBPB JUND SPI1 GATA3 TMTC2 ENSG00000286043 piR-38351-107
GH12J082649 Enhancer 1 Ensembl ENCODE 6.6 -35.9 -35856 2.8 ZNF217 ZSCAN5C TCF12 JUND ZNF10 EP300 ZIC2 TRIM28 KLF4 KLF7 TMTC2 piR-38351-107 ENSG00000286043
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TMTC2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TMTC2

Top Transcription factor binding sites by QIAGEN in the TMTC2 gene promoter:
  • c-Myc
  • Hlf
  • HNF-3beta
  • Max1
  • MyoD
  • NF-kappaB1
  • NF-kappaB2
  • POU3F1
  • S8
  • TGIF

Genomic Locations for TMTC2 Gene

Genomic Locations for TMTC2 Gene
chr12:82,686,880-83,134,870
(GRCh38/hg38)
Size:
447,991 bases
Orientation:
Plus strand
chr12:83,080,659-83,528,649
(GRCh37/hg19)
Size:
447,991 bases
Orientation:
Plus strand

Genomic View for TMTC2 Gene

Genes around TMTC2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TMTC2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TMTC2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TMTC2 Gene

Proteins for TMTC2 Gene

  • Protein details for TMTC2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8N394-TMTC2_HUMAN
    Recommended name:
    Protein O-mannosyl-transferase TMTC2
    Protein Accession:
    Q8N394
    Secondary Accessions:
    • B2RCU7
    • Q8N2K8

    Protein attributes for TMTC2 Gene

    Size:
    836 amino acids
    Molecular mass:
    94130 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=BAC11102.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

neXtProt entry for TMTC2 Gene

Post-translational modifications for TMTC2 Gene

  • Glycosylation at Asn221
  • Modification sites at PhosphoSitePlus

Other Protein References for TMTC2 Gene

No data available for DME Specific Peptides for TMTC2 Gene

Domains & Families for TMTC2 Gene

Protein Domains for TMTC2 Gene

Suggested Antigen Peptide Sequences for TMTC2 Gene

GenScript: Design optimal peptide antigens:
  • Transmembrane and TPR repeat-containing protein 2 (TMTC2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8N394

UniProtKB/Swiss-Prot:

TMTC2_HUMAN :
  • Belongs to the TMTC family.
Family:
  • Belongs to the TMTC family.
genes like me logo Genes that share domains with TMTC2: view

Function for TMTC2 Gene

Molecular function for TMTC2 Gene

UniProtKB/Swiss-Prot Function:
Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. The 4 members of the TMTC family are O-mannosyl-transferases dedicated primarily to the cadherin superfamily, each member seems to have a distinct role in decorating the cadherin domains with O-linked mannose glycans at specific regions. Also acts as O-mannosyl-transferase on other proteins such as PDIA3.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=dolichyl beta-D-mannosyl phosphate + L-seryl-[protein] = 3-O-(alpha-D-mannosyl)-L-seryl-[protein] + dolichyl phosphate + H(+); Xref=Rhea:RHEA:17377, Rhea:RHEA-COMP:9517, Rhea:RHEA-COMP:9527, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:13546, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:57683, ChEBI:CHEBI:58211, ChEBI:CHEBI:137321; EC=2.4.1.109; Evidence=. ; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17378; Evidence=. ;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=dolichyl beta-D-mannosyl phosphate + L-threonyl-[protein] = 3-O-(alpha-D-mannosyl)-L-threonyl-[protein] + dolichyl phosphate + H(+); Xref=Rhea:RHEA:53396, Rhea:RHEA-COMP:9517, Rhea:RHEA-COMP:9527, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:13547, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:57683, ChEBI:CHEBI:58211, ChEBI:CHEBI:137323; EC=2.4.1.109; Evidence=. ; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53397; Evidence=. ;.

Enzyme Numbers (IUBMB) for TMTC2 Gene

Phenotypes From GWAS Catalog for TMTC2 Gene

Gene Ontology (GO) - Molecular Function for TMTC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000030 mannosyltransferase activity IMP 28973932
GO:0004169 dolichyl-phosphate-mannose-protein mannosyltransferase activity IEA --
GO:0005515 protein binding IEA,IPI 24764305
GO:0016740 transferase activity IEA --
genes like me logo Genes that share ontologies with TMTC2: view
genes like me logo Genes that share phenotypes with TMTC2: view

Animal Model Products

CRISPR Products

Clone Products

  • Addgene plasmids for TMTC2

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for TMTC2 Gene

Localization for TMTC2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TMTC2 Gene

Membrane; Multi-pass membrane protein. Endoplasmic reticulum.

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 TMTC2 gene
Compartment Confidence
endoplasmic reticulum 5
plasma membrane 2
cytoskeleton 2
cytosol 2
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Actin filaments (2)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for TMTC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IDA --
GO:0005789 endoplasmic reticulum membrane IDA 24764305
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with TMTC2: view

Pathways & Interactions for TMTC2 Gene

PathCards logo

SuperPathways for TMTC2 Gene

No Data Available

UniProtKB/Swiss-Prot Q8N394-TMTC2_HUMAN

  • Pathway: Protein modification; protein glycosylation.

Gene Ontology (GO) - Biological Process for TMTC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006486 protein glycosylation IEA --
GO:0035269 protein O-linked mannosylation IMP 28973932
GO:0055074 calcium ion homeostasis IMP 24764305
genes like me logo Genes that share ontologies with TMTC2: view

No data available for Pathways by source and SIGNOR curated interactions for TMTC2 Gene

Drugs & Compounds for TMTC2 Gene

No Compound Related Data Available

Transcripts for TMTC2 Gene

mRNA/cDNA for TMTC2 Gene

3 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for TMTC2

Alternative Splicing Database (ASD) splice patterns (SP) for TMTC2 Gene

No ASD Table

Relevant External Links for TMTC2 Gene

GeneLoc Exon Structure for
TMTC2

Expression for TMTC2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TMTC2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for TMTC2 Gene

This gene is overexpressed in Brain - Spinal cord (cervical c-1) (x4.1).

Protein differential expression in normal tissues from HIPED for TMTC2 Gene

This gene is overexpressed in Liver (49.6) and Frontal cortex (16.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for TMTC2 Gene



Protein tissue co-expression partners for TMTC2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TMTC2

SOURCE GeneReport for Unigene cluster for TMTC2 Gene:

Hs.577775

Evidence on tissue expression from TISSUES for TMTC2 Gene

  • Nervous system(4.7)
genes like me logo Genes that share expression patterns with TMTC2: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for TMTC2 Gene

Orthologs for TMTC2 Gene

This gene was present in the common ancestor of animals.

Orthologs for TMTC2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TMTC2 31 30
  • 99.4 (n)
OneToOne
cow
(Bos Taurus)
Mammalia TMTC2 31 30
  • 92.42 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia TMTC2 31
  • 90 (a)
OneToOne
dog
(Canis familiaris)
Mammalia TMTC2 31 30
  • 89.67 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Tmtc2 17 31 30
  • 88.8 (n)
rat
(Rattus norvegicus)
Mammalia Tmtc2 30
  • 88.56 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia TMTC2 31
  • 87 (a)
OneToOne
chicken
(Gallus gallus)
Aves TMTC2 31 30
  • 81.28 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TMTC2 31
  • 83 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia tmtc2 30
  • 76.44 (n)
zebrafish
(Danio rerio)
Actinopterygii TMTC2 (1 of 2) 31
  • 75 (a)
OneToMany
tmtc2 31 30
  • 66.51 (n)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009112 30
  • 50.29 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG4341 31 30
  • 48.28 (n)
OneToMany
CG31690 31
  • 35 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea F32D1.3 31 30
  • 43.7 (n)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 39 (a)
OneToOne
Species where no ortholog for TMTC2 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 TMTC2 Gene

ENSEMBL:
Gene Tree for TMTC2 (if available)
TreeFam:
Gene Tree for TMTC2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TMTC2: view image

Paralogs for TMTC2 Gene

(3) SIMAP similar genes for TMTC2 Gene using alignment to 3 proteins:

  • TMTC2_HUMAN
  • F8VRQ2_HUMAN
  • F8VSH2_HUMAN
genes like me logo Genes that share paralogs with TMTC2: view

Variants for TMTC2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TMTC2 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
707900 Benign: not provided 82,895,995(+) A/G MISSENSE_VARIANT
748483 Benign: not provided 82,687,640(+) C/T SYNONYMOUS_VARIANT,FIVE_PRIME_UTR_VARIANT
773663 Benign: not provided 83,132,311(+) C/T SYNONYMOUS_VARIANT
rs1201791 - p.Ala315Thr
rs17010106 - p.Tyr443Ser

Additional dbSNP identifiers (rs#s) for TMTC2 Gene

Structural Variations from Database of Genomic Variants (DGV) for TMTC2 Gene

Variant ID Type Subtype PubMed ID
dgv1531n100 CNV loss 25217958
dgv1532n100 CNV loss 25217958
dgv2742n54 CNV loss 21841781
dgv2743n54 CNV loss 21841781
dgv2744n54 CNV loss 21841781
dgv33e180 CNV loss 20482838
dgv496e212 CNV loss 25503493
esv1003105 CNV deletion 20482838
esv1008305 CNV loss 20482838
esv1011810 CNV insertion 17803354
esv1419949 CNV insertion 17803354
esv2016291 CNV deletion 18987734
esv2421910 CNV deletion 20811451
esv2663704 CNV deletion 23128226
esv2746123 CNV deletion 23290073
esv2746124 CNV deletion 23290073
esv2746125 CNV deletion 23290073
esv2746126 CNV deletion 23290073
esv2759911 CNV loss 17122850
esv2760276 CNV loss 21179565
esv2760932 CNV loss 21179565
esv2889346 CNV deletion 24192839
esv29204 CNV loss 19812545
esv30004 CNV loss 17803354
esv3549491 CNV deletion 23714750
esv3580357 CNV loss 25503493
esv3630165 CNV loss 21293372
esv3630166 CNV loss 21293372
esv3630167 CNV gain 21293372
esv3630168 CNV loss 21293372
esv3630169 CNV loss 21293372
esv3630170 CNV loss 21293372
esv3630171 CNV loss 21293372
esv3892233 CNV loss 25118596
esv3892234 CNV gain 25118596
esv5126 CNV loss 18987735
esv9165 CNV gain 19470904
esv999149 CNV loss 20482838
nsv1047239 CNV gain 25217958
nsv1128670 CNV duplication 24896259
nsv1148112 CNV insertion 26484159
nsv437765 CNV loss 16327808
nsv442650 CNV loss 18776908
nsv469490 CNV loss 19166990
nsv469491 CNV loss 19166990
nsv469492 CNV loss 19166990
nsv469494 CNV loss 19166990
nsv469495 CNV loss 19166990
nsv477129 CNV novel sequence insertion 20440878
nsv480892 CNV novel sequence insertion 20440878
nsv507662 OTHER sequence alteration 20534489
nsv516625 CNV loss 19592680
nsv521849 CNV gain 19592680
nsv523902 CNV loss 19592680
nsv559541 CNV gain 21841781
nsv559542 CNV loss 21841781
nsv559543 CNV loss 21841781
nsv559556 CNV loss 21841781
nsv559557 CNV loss 21841781
nsv559558 CNV loss 21841781
nsv559559 CNV gain 21841781
nsv818928 CNV loss 17921354
nsv832472 CNV loss 17160897

Variation tolerance for TMTC2 Gene

Residual Variation Intolerance Score: 26.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.41; 63.81% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TMTC2 Gene

Human Gene Mutation Database (HGMD)
TMTC2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TMTC2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TMTC2 Gene

Disorders for TMTC2 Gene

MalaCards: The human disease database

(5) MalaCards diseases for TMTC2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
auditory neuropathy, autosomal dominant, 1
  • auna1
open-angle glaucoma
  • glaucoma simplex
deafness, autosomal recessive 84a
  • dfnb84a
glaucoma, primary open angle
  • poag
glaucoma, normal tension
  • glaucoma, normal tension, susceptibility to
- elite association - COSMIC cancer census association via MalaCards
Search TMTC2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for TMTC2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with TMTC2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TMTC2 Gene

Publications for TMTC2 Gene

  1. Discovery of an O-mannosylation pathway selectively serving cadherins and protocadherins. (PMID: 28973932) Larsen ISB … Halim A (Proceedings of the National Academy of Sciences of the United States of America 2017) 3 4 54
  2. TMTC1 and TMTC2 are novel endoplasmic reticulum tetratricopeptide repeat-containing adapter proteins involved in calcium homeostasis. (PMID: 24764305) Sunryd JC … Hebert DN (The Journal of biological chemistry 2014) 2 3 54
  3. A genome-wide search for loci interacting with known prostate cancer risk-associated genetic variants. (PMID: 22219177) Tao S … Sun J (Carcinogenesis 2012) 3 41 54
  4. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41 54
  5. Three susceptible loci associated with primary open-angle glaucoma identified by genome-wide association study in a Japanese population. (PMID: 19625618) Nakano M … Tashiro K (Proceedings of the National Academy of Sciences of the United States of America 2009) 3 41 54

Products for TMTC2 Gene

Sources for TMTC2 Gene