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Aliases for TMTC3 Gene

Aliases for TMTC3 Gene

  • Transmembrane And Tetratricopeptide Repeat Containing 3 2 3 5
  • Transmembrane And TPR Repeat-Containing Protein 3 3
  • Protein SMILE 4
  • SMILE 3
  • LIS8 3

External Ids for TMTC3 Gene

Previous GeneCards Identifiers for TMTC3 Gene

  • GC12P087042
  • GC12P088536
  • GC12P085603

Summaries for TMTC3 Gene

Entrez Gene Summary for TMTC3 Gene

  • This gene encodes a protein that belongs to the transmembrane and tetratricopeptide repeat-containing protein family. [provided by RefSeq, May 2010]

GeneCards Summary for TMTC3 Gene

TMTC3 (Transmembrane And Tetratricopeptide Repeat Containing 3) is a Protein Coding gene. Diseases associated with TMTC3 include Lissencephaly 8 and Periventricular Nodular Heterotopia. An important paralog of this gene is TMTC4.

UniProtKB/Swiss-Prot for TMTC3 Gene

  • Involved in the positive regulation of proteasomal protein degradation in the endoplasmic reticulum (ER), and the control of ER stress response.

Additional gene information for TMTC3 Gene

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TMTC3 Gene

Genomics for TMTC3 Gene

GeneHancer (GH) Regulatory Elements for TMTC3 Gene

Promoters and enhancers for TMTC3 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
GH12I088141 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 550.8 +0.2 192 2.7 HDGF PKNOX1 MLX ARNT ZFP64 ARID4B SIN3A DMAP1 ZNF2 YY1 CEP290 TMTC3 PIR56802
GH12I088034 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 9.1 -106.3 -106280 2.4 HDGF PKNOX1 CLOCK MLX ARNT ARID4B SIN3A FEZF1 DMAP1 ZNF2 C12orf29 C12orf50 CEP290 TMTC3 RNA5SP364
GH12I088297 Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 9.3 +157.3 157344 3.8 PKNOX1 FOXA2 IRF4 YY1 ATF7 FOS RUNX3 RXRA JUNB REST TMTC3 C12orf29 LOC101929554 GC12P088431
GH12I087157 Enhancer 0.6 ENCODE 16.4 -984.3 -984347 0.2 STAT1 BDP1 JUN CEBPB EP300 RAD21 SP1 GTF3C2 JUND POLR3A TMTC3 CEP290 LOC100420011 GC12M087170 LOC105369878
GH12I088241 Enhancer 0.9 Ensembl ENCODE 10.5 +100.3 100300 1.7 JUN MAX BATF ZBTB40 FOSL1 ZNF366 POLR2A FOSL2 FOS RUNX3 TMTC3 LOC101929554 GC12P088431
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around TMTC3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the TMTC3 gene promoter:

Genomic Locations for TMTC3 Gene

Genomic Locations for TMTC3 Gene
57,592 bases
Plus strand

Genomic View for TMTC3 Gene

Genes around TMTC3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TMTC3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TMTC3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TMTC3 Gene

Proteins for TMTC3 Gene

  • Protein details for TMTC3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Transmembrane and TPR repeat-containing protein 3
    Protein Accession:
    Secondary Accessions:
    • Q5CZ86
    • Q5H9T6
    • Q68DQ6
    • Q68DX0
    • Q7Z332
    • Q8NC50

    Protein attributes for TMTC3 Gene

    915 amino acids
    Molecular mass:
    104009 Da
    Quaternary structure:
    No Data Available
    • Sequence=BAC11325.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for TMTC3 Gene


neXtProt entry for TMTC3 Gene

Post-translational modifications for TMTC3 Gene

  • Ubiquitination at posLast=460460 and isoforms=2738
  • Glycosylation at isoforms=2117, isoforms=2494, posLast=541541, and isoforms=2844
  • Modification sites at PhosphoSitePlus

Other Protein References for TMTC3 Gene

No data available for DME Specific Peptides for TMTC3 Gene

Domains & Families for TMTC3 Gene

Gene Families for TMTC3 Gene

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

Protein Domains for TMTC3 Gene

Suggested Antigen Peptide Sequences for TMTC3 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the TMTC family.
  • Belongs to the TMTC family.
genes like me logo Genes that share domains with TMTC3: view

Function for TMTC3 Gene

Molecular function for TMTC3 Gene

UniProtKB/Swiss-Prot Function:
Involved in the positive regulation of proteasomal protein degradation in the endoplasmic reticulum (ER), and the control of ER stress response.

Phenotypes From GWAS Catalog for TMTC3 Gene

Gene Ontology (GO) - Molecular Function for TMTC3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 25416956
genes like me logo Genes that share ontologies with TMTC3: view
genes like me logo Genes that share phenotypes with TMTC3: view

Human Phenotype Ontology for TMTC3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

miRNA for TMTC3 Gene

miRTarBase miRNAs that target TMTC3

Clone Products

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for TMTC3 Gene

Localization for TMTC3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TMTC3 Gene

Membrane; Multi-pass membrane protein. Endoplasmic reticulum. Note=In odontoblast cultures, it colocalizes with PDIA3 in the endoplasmic reticulum. {ECO:0000269 PubMed:21603654}.

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 TMTC3 gene
Compartment Confidence
endoplasmic reticulum 5
cytoskeleton 2
plasma membrane 1

Gene Ontology (GO) - Cellular Components for TMTC3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IDA,IEA 21603654
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with TMTC3: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TMTC3 Gene

Pathways & Interactions for TMTC3 Gene

SuperPathways for TMTC3 Gene

No Data Available

Gene Ontology (GO) - Biological Process for TMTC3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0034976 response to endoplasmic reticulum stress IMP 21603654
GO:1901800 positive regulation of proteasomal protein catabolic process IMP 21603654
genes like me logo Genes that share ontologies with TMTC3: view

No data available for Pathways by source and SIGNOR curated interactions for TMTC3 Gene

Drugs & Compounds for TMTC3 Gene

No Compound Related Data Available

Transcripts for TMTC3 Gene

Unigene Clusters for TMTC3 Gene

Transmembrane and tetratricopeptide repeat containing 3:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for TMTC3 Gene

No ASD Table

Relevant External Links for TMTC3 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for TMTC3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for TMTC3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for TMTC3 Gene

This gene is overexpressed in Nasal epithelium (26.5), Breast (17.2), and Cervix (8.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for TMTC3 Gene

NURSA nuclear receptor signaling pathways regulating expression of TMTC3 Gene:


SOURCE GeneReport for Unigene cluster for TMTC3 Gene:


Evidence on tissue expression from TISSUES for TMTC3 Gene

  • Nervous system(4.3)
  • Intestine(4.2)
genes like me logo Genes that share expression patterns with TMTC3: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for TMTC3 Gene

Orthologs for TMTC3 Gene

This gene was present in the common ancestor of animals.

Orthologs for TMTC3 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia TMTC3 33 34
  • 99.78 (n)
(Canis familiaris)
Mammalia TMTC3 33 34
  • 93.29 (n)
(Bos Taurus)
Mammalia TMTC3 33 34
  • 92.38 (n)
(Rattus norvegicus)
Mammalia Tmtc3 33
  • 86.67 (n)
(Monodelphis domestica)
Mammalia TMTC3 34
  • 86 (a)
(Mus musculus)
Mammalia Tmtc3 33 16 34
  • 85.54 (n)
(Ornithorhynchus anatinus)
Mammalia TMTC3 34
  • 83 (a)
(Gallus gallus)
Aves TMTC3 33 34
  • 78.44 (n)
(Anolis carolinensis)
Reptilia TMTC3 34
  • 84 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.10499 33
(Danio rerio)
Actinopterygii tmtc3 33 34
  • 66.45 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP010599 33
  • 56.36 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG4050 33 34
  • 53.84 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 42 (a)
Species where no ortholog for TMTC3 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)
  • worm (Caenorhabditis elegans)

Evolution for TMTC3 Gene

Gene Tree for TMTC3 (if available)
Gene Tree for TMTC3 (if available)

Paralogs for TMTC3 Gene

Paralogs for TMTC3 Gene

(3) SIMAP similar genes for TMTC3 Gene using alignment to 5 proteins:

genes like me logo Genes that share paralogs with TMTC3: view

Variants for TMTC3 Gene

Sequence variations from dbSNP and Humsavar for TMTC3 Gene

SNP ID Clin Chr 12 pos Variation AA Info Type
rs1057517696 pathogenic, Lissencephaly 8 88,188,871(+) AA/A coding_sequence_variant, frameshift
rs1057517697 pathogenic, Lissencephaly 8 88,195,521(+) C/T coding_sequence_variant, stop_gained
rs1057517698 pathogenic, Lissencephaly 8 88,148,318(+) G/A genic_upstream_transcript_variant, initiator_codon_variant, missense_variant
rs1057519417 pathogenic, Lissencephaly 8 88,194,863(+) T/TTT coding_sequence_variant, frameshift
rs139415563 uncertain-significance, Meckel-Gruber syndrome, Renal dysplasia and retinal aplasia, Leber congenital amaurosis, Bardet-Biedl syndrome, Joubert syndrome 88,141,905(+) C/A upstream_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for TMTC3 Gene

Variant ID Type Subtype PubMed ID
nsv1132853 CNV insertion 24896259
nsv483111 CNV loss 15286789
nsv807 CNV deletion 18451855
nsv826471 CNV loss 20364138
nsv826472 CNV gain 20364138

Variation tolerance for TMTC3 Gene

Residual Variation Intolerance Score: 11.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.91; 74.35% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TMTC3 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 TMTC3 Gene

Disorders for TMTC3 Gene

MalaCards: The human disease database

(5) MalaCards diseases for TMTC3 Gene - From: HGMD, OMIM, ClinVar, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
lissencephaly 8
  • lis8
periventricular nodular heterotopia
  • periventricular heterotopia
  • broad gyri of cerebrum
walker-warburg syndrome
  • cerebroocular dysplasia-muscular dystrophy syndrome
- elite association - COSMIC cancer census association via MalaCards
Search TMTC3 in MalaCards View complete list of genes associated with diseases


  • Lissencephaly 8 (LIS8) [MIM:617255]: A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS8 patients manifest delayed psychomotor development, intellectual disability with poor or absent speech, early-onset refractory seizures, hypotonia, cortical gyral abnormalities, and hypoplasia of the corpus callosum, brainstem and cerebellum. LIS8 inheritance is autosomal recessive. {ECO:0000269 PubMed:27773428}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for TMTC3

genes like me logo Genes that share disorders with TMTC3: view

No data available for Genatlas for TMTC3 Gene

Publications for TMTC3 Gene

  1. The involvement of SMILE/TMTC3 in endoplasmic reticulum stress response. (PMID: 21603654) Racapé M … Brouard S (PloS one 2011) 3 4 58
  2. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4 58
  3. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 58
  4. Architecture of the human interactome defines protein communities and disease networks. (PMID: 28514442) Huttlin EL … Harper JW (Nature 2017) 3 58
  5. Biallelic Mutations in TMTC3, Encoding a Transmembrane and TPR-Containing Protein, Lead to Cobblestone Lissencephaly. (PMID: 27773428) Jerber J … Gleeson JG (American journal of human genetics 2016) 4 58

Products for TMTC3 Gene

Sources for TMTC3 Gene

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