This locus encodes a transmembrane protein. Mutations at this locus have been associated with craniofacial dysmorphism, skeletal anomalies, and cognitive disability. Mutations at this locus have also been associated with open angle glaucoma blindness. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2012] See more...

Aliases for TMCO1 Gene

Aliases for TMCO1 Gene

  • Transmembrane And Coiled-Coil Domains 1 2 3 5
  • Transmembrane And Coiled-Coil Domain-Containing Protein 1 3 4
  • Transmembrane And Coiled-Coil Domains 4 2 3
  • Calcium Load-Activated Calcium Channel 3 4
  • Xenogeneic Cross-Immune Protein PCIA3 3 4
  • Ca(2+) Load-Activated Ca(2+) Channel 2 3
  • CLAC Channel 3 4
  • TMCC4 3 4
  • Transmembrane And Coiled-Coil Domains Protein 4 4
  • Putative Membrane Protein 3
  • PNAS-136 3
  • HP10122 3
  • PCIA3 3

External Ids for TMCO1 Gene

Previous HGNC Symbols for TMCO1 Gene

  • TMCC4

Previous GeneCards Identifiers for TMCO1 Gene

  • GC01M162429
  • GC01M163962
  • GC01M165693
  • GC01M136941

Summaries for TMCO1 Gene

Entrez Gene Summary for TMCO1 Gene

  • This locus encodes a transmembrane protein. Mutations at this locus have been associated with craniofacial dysmorphism, skeletal anomalies, and cognitive disability. Mutations at this locus have also been associated with open angle glaucoma blindness. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2012]

GeneCards Summary for TMCO1 Gene

TMCO1 (Transmembrane And Coiled-Coil Domains 1) is a Protein Coding gene. Diseases associated with TMCO1 include Craniofacial Dysmorphism, Skeletal Anomalies, And Mental Retardation Syndrome and Pulmonic Stenosis.

UniProtKB/Swiss-Prot Summary for TMCO1 Gene

  • Calcium-selective channel required to prevent calcium stores from overfilling, thereby playing a key role in calcium homeostasis (PubMed:27212239). In response to endoplasmic reticulum overloading, assembles into a homotetramer, forming a functional calcium-selective channel, regulating the calcium content in endoplasmic reticulum store (PubMed:27212239).

Gene Wiki entry for TMCO1 Gene

Additional gene information for TMCO1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TMCO1 Gene

Genomics for TMCO1 Gene

GeneHancer (GH) Regulatory Elements for TMCO1 Gene

Promoters and enhancers for TMCO1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TMCO1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TMCO1

Top Transcription factor binding sites by QIAGEN in the TMCO1 gene promoter:
  • AhR
  • Elk-1
  • GATA-2
  • Meis-1
  • Meis-1a
  • Meis-1b
  • Pax-4a
  • PPAR-gamma1
  • PPAR-gamma2

Genomic Locations for TMCO1 Gene

Genomic Locations for TMCO1 Gene
chr1:165,724,291-165,827,755
(GRCh38/hg38)
Size:
103,465 bases
Orientation:
Minus strand
chr1:165,693,528-165,796,992
(GRCh37/hg19)
Size:
103,465 bases
Orientation:
Minus strand

Genomic View for TMCO1 Gene

Genes around TMCO1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TMCO1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TMCO1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TMCO1 Gene

Proteins for TMCO1 Gene

  • Protein details for TMCO1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UM00-TMCO1_HUMAN
    Recommended name:
    Calcium load-activated calcium channel
    Protein Accession:
    Q9UM00
    Secondary Accessions:
    • B2REA0
    • J9JIE6
    • O75545
    • Q9BZS3
    • Q9BZU8

    Protein attributes for TMCO1 Gene

    Size:
    239 amino acids
    Molecular mass:
    27079 Da
    Quaternary structure:
    • Homodimer and homotetramer (PubMed:27212239). Homodimer under resting conditions; forms homotetramers following and endoplasmic reticulum calcium overload (PubMed:27212239).
    SequenceCaution:
    • Sequence=AAK07514.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAK07549.1; Type=Frameshift; Evidence={ECO:0000305};

    Alternative splice isoforms for TMCO1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TMCO1 Gene

Post-translational modifications for TMCO1 Gene

  • Ubiquitination at Lys116 and Lys186
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for TMCO1 Gene

Domains & Families for TMCO1 Gene

Gene Families for TMCO1 Gene

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

Protein Domains for TMCO1 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for TMCO1 Gene

GenScript: Design optimal peptide antigens:
  • cDNA, FLJ78979, highly similar to Transmembrane and coiled-coil domains protein 1 (B7Z591_HUMAN)
  • Xenogeneic cross-immune protein PCIA3 (TMCO1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9UM00

UniProtKB/Swiss-Prot:

TMCO1_HUMAN :
  • Belongs to the TMCO1 family.
Family:
  • Belongs to the TMCO1 family.
genes like me logo Genes that share domains with TMCO1: view

Function for TMCO1 Gene

Molecular function for TMCO1 Gene

UniProtKB/Swiss-Prot Function:
Calcium-selective channel required to prevent calcium stores from overfilling, thereby playing a key role in calcium homeostasis (PubMed:27212239). In response to endoplasmic reticulum overloading, assembles into a homotetramer, forming a functional calcium-selective channel, regulating the calcium content in endoplasmic reticulum store (PubMed:27212239).

Phenotypes From GWAS Catalog for TMCO1 Gene

Gene Ontology (GO) - Molecular Function for TMCO1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005262 calcium channel activity IEA,IDA 27212239
genes like me logo Genes that share ontologies with TMCO1: view
genes like me logo Genes that share phenotypes with TMCO1: view

Human Phenotype Ontology for TMCO1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

  • Taconic Biosciences Mouse Models for TMCO1

CRISPR Products

miRNA for TMCO1 Gene

miRTarBase miRNAs that target TMCO1

Clone Products

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for TMCO1 Gene

Localization for TMCO1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TMCO1 Gene

Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein. Note=The first transmembrane region is required for localization to the endoplasmic reticulum (PubMed:27212239). A publication reported localization in cytoplasm and nucleus (PubMed:22714896). Nuclear localization is however in contradiction with two other reports (PubMed:10393320, PubMed:27212239). {ECO:0000269 PubMed:10393320, ECO:0000269 PubMed:22714896, ECO:0000269 PubMed:27212239}.

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 TMCO1 gene
Compartment Confidence
endoplasmic reticulum 5
extracellular 3
golgi apparatus 3
plasma membrane 2
cytoskeleton 1
mitochondrion 1
nucleus 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Endoplasmic reticulum (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for TMCO1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane IEA --
GO:0005783 endoplasmic reticulum IEA,IDA --
GO:0005789 endoplasmic reticulum membrane IEA --
GO:0005794 Golgi apparatus IEA --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with TMCO1: view

Pathways & Interactions for TMCO1 Gene

PathCards logo

SuperPathways for TMCO1 Gene

No Data Available

Gene Ontology (GO) - Biological Process for TMCO1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0006816 calcium ion transport IEA --
GO:0006983 ER overload response IDA 27212239
GO:0032469 endoplasmic reticulum calcium ion homeostasis IDA,IEA 27212239
GO:0070588 calcium ion transmembrane transport IDA,IEA 27212239
genes like me logo Genes that share ontologies with TMCO1: view

No data available for Pathways by source and SIGNOR curated interactions for TMCO1 Gene

Drugs & Compounds for TMCO1 Gene

No Compound Related Data Available

Transcripts for TMCO1 Gene

mRNA/cDNA for TMCO1 Gene

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

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for TMCO1 Gene

ExUns: 1a · 1b · 1c · 1d · 1e · 1f · 1g ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8a · 8b · 8c · 8d
SP1: - -
SP2: - - -
SP3: -
SP4: - - -
SP5: - - -
SP6: - - -
SP7: -

Relevant External Links for TMCO1 Gene

GeneLoc Exon Structure for
TMCO1

Expression for TMCO1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TMCO1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for TMCO1 Gene

This gene is overexpressed in Nasal epithelium (50.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for TMCO1 Gene



Protein tissue co-expression partners for TMCO1 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TMCO1

SOURCE GeneReport for Unigene cluster for TMCO1 Gene:

Hs.31498

mRNA Expression by UniProt/SwissProt for TMCO1 Gene:

Q9UM00-TMCO1_HUMAN
Tissue specificity: Widely expressed in adult and fetal tissues, with higher levels in thymus, prostate, testis and small intestine and lower levels in brain, placenta, lung and kidney (PubMed:10393320, PubMed:20018682). Present in most tissues in the eye, including the trabecular meshwork and retina (at protein level) (PubMed:22714896).

Evidence on tissue expression from TISSUES for TMCO1 Gene

  • Nervous system(4.9)
  • Lung(3.7)
  • Kidney(3.5)
  • Eye(2.7)
  • Pancreas(2.6)
  • Liver(2.1)
  • Intestine(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for TMCO1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cerebellum
  • chin
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • mouth
  • neck
  • nose
  • outer ear
  • scalp
  • skull
  • tooth
Thorax:
  • breast
  • chest wall
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • abdominal wall
  • intestine
Pelvis:
  • pelvis
  • penis
  • placenta
  • testicle
  • uterus
Limb:
  • digit
  • finger
  • hand
  • upper limb
General:
  • hair
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • spinal cord
  • vertebrae
genes like me logo Genes that share expression patterns with TMCO1: view

No data available for mRNA differential expression in normal tissues for TMCO1 Gene

Orthologs for TMCO1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for TMCO1 Gene

Organism Taxonomy Gene Similarity Type Details
dog
(Canis familiaris)
Mammalia TMCO1 31
  • 100 (a)
OneToOne
LOC478992 30
  • 87.76 (n)
chimpanzee
(Pan troglodytes)
Mammalia TMCO1 31 30
  • 99.72 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia TMCO1 31
  • 97 (a)
OneToOne
cow
(Bos Taurus)
Mammalia TMCO1 31 30
  • 93.62 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TMCO1 31
  • 93 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Tmco1 30
  • 91.13 (n)
mouse
(Mus musculus)
Mammalia Tmco1 17 31 30
  • 90.6 (n)
chicken
(Gallus gallus)
Aves TMCO1 31 30
  • 83.87 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TMCO1 31
  • 93 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia tmco1 30
  • 78.72 (n)
Str.6955 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.25231 30
zebrafish
(Danio rerio)
Actinopterygii tmco1 31 30
  • 76.6 (n)
OneToOne
sbcb729 30
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009081 30
  • 69.85 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG10470 31 30
  • 65.93 (n)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea F22B5.10 31 30
  • 61.99 (n)
OneToOne
thale cress
(Arabidopsis thaliana)
eudicotyledons AT5G06660 30
  • 53.37 (n)
rice
(Oryza sativa)
Liliopsida Os03g0721400 30
  • 49.72 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.5121 31
  • 69 (a)
OneToOne
Cin.3701 30
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.3701 30
Species where no ortholog for TMCO1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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 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)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for TMCO1 Gene

ENSEMBL:
Gene Tree for TMCO1 (if available)
TreeFam:
Gene Tree for TMCO1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TMCO1: view image

Paralogs for TMCO1 Gene

(1) SIMAP similar genes for TMCO1 Gene using alignment to 8 proteins:

  • TMCO1_HUMAN
  • B7Z591_HUMAN
  • J3KS45_HUMAN
  • J3KTQ7_HUMAN
  • J3QQY2_HUMAN
  • J3QRB3_HUMAN
  • J9JIE6_HUMAN
  • L8EA41_HUMAN
genes like me logo Genes that share paralogs with TMCO1: view

No data available for Paralogs for TMCO1 Gene

Variants for TMCO1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TMCO1 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
737458 Benign: not provided 165,768,817(-) A/G MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,FIVE_PRIME_UTR_VARIANT
767722 Benign: not provided 165,743,318(-) GA/G INTRON_VARIANT
770495 Benign: not provided 165,743,318(-) G/GA INTRON_VARIANT
rs1247427997 Pathogenic: Inborn genetic diseases 165,743,244(-) G/A NONSENSE,NON_CODING_TRANSCRIPT_VARIANT
rs1553249737 Pathogenic: Inborn genetic diseases 165,743,263(-) G/T NONSENSE,NON_CODING_TRANSCRIPT_VARIANT

Additional dbSNP identifiers (rs#s) for TMCO1 Gene

Structural Variations from Database of Genomic Variants (DGV) for TMCO1 Gene

Variant ID Type Subtype PubMed ID
dgv218n106 CNV deletion 24896259
esv2177447 CNV deletion 18987734
esv2520993 CNV deletion 19546169
esv2719106 CNV deletion 23290073
esv3542056 CNV deletion 23714750
esv5064 CNV loss 18987735
esv6923 CNV loss 19470904
nsv1079026 CNV deletion 25765185
nsv159176 CNV deletion 16902084
nsv518886 CNV gain 19592680
nsv957287 CNV deletion 24416366

Variation tolerance for TMCO1 Gene

Residual Variation Intolerance Score: 40% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.50; 55.35% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TMCO1 Gene

Human Gene Mutation Database (HGMD)
TMCO1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TMCO1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TMCO1 Gene

Disorders for TMCO1 Gene

MalaCards: The human disease database

(21) MalaCards diseases for TMCO1 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search TMCO1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TMCO1_HUMAN
  • Craniofacial dysmorphism, skeletal anomalies and mental retardation syndrome (CFSMR) [MIM:213980]: A disorder characterized by craniofacial and skeletal anomalies, associated with mental retardation. Typical craniofacial dysmorphism include brachycephaly, highly arched bushy eyebrows, synophrys, long eyelashes, low-set ears, microdontism of primary teeth, and generalized gingival hyperplasia, whereas Sprengel deformity of scapula, fusion of spine, rib abnormities, pectus excavatum, and pes planus represent skeletal anomalies. {ECO:0000269 PubMed:20018682, ECO:0000269 PubMed:23320496, ECO:0000269 PubMed:24194475}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Glaucoma, primary open angle (POAG) [MIM:137760]: A complex and genetically heterogeneous ocular disorder characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. In some cases, POAG shows digenic inheritance involving mutations in CYP1B1 and MYOC genes. {ECO:0000269 PubMed:21532571, ECO:0000269 PubMed:22714896}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Additional Disease Information for TMCO1

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 TMCO1: view

No data available for Genatlas for TMCO1 Gene

Publications for TMCO1 Gene

  1. TMCO1 Is an ER Ca(2+) Load-Activated Ca(2+) Channel. (PMID: 27212239) Wang QC … Tang TS (Cell 2016) 2 3 4 54
  2. TMCO1 deficiency causes autosomal recessive cerebrofaciothoracic dysplasia. (PMID: 24194475) Alanay Y … Akarsu NA (American journal of medical genetics. Part A 2014) 3 4 54
  3. Association of genetic variants in the TMCO1 gene with clinical parameters related to glaucoma and characterization of the protein in the eye. (PMID: 22714896) Sharma S … Craig JE (Investigative ophthalmology & visual science 2012) 3 4 54
  4. Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1. (PMID: 21532571) Burdon KP … Craig JE (Nature genetics 2011) 3 4 54
  5. Homozygous frameshift mutation in TMCO1 causes a syndrome with craniofacial dysmorphism, skeletal anomalies, and mental retardation. (PMID: 20018682) Xin B … Wang H (Proceedings of the National Academy of Sciences of the United States of America 2010) 3 4 54

Products for TMCO1 Gene

Sources for TMCO1 Gene