Voltage-gated Ca(2+) and Na+ channels have 4 homologous domains, each containing 6 transmembrane segments, S1 to S6. TPCN1 is similar to these channels, but it has only 2 domains containing S1 to S6 (Ishibashi et al., 2000 [PubMed 10753632]).[supplied by OMIM, Mar 2008] See more...

Aliases for TPCN1 Gene

Aliases for TPCN1 Gene

  • Two Pore Segment Channel 1 2 3 5
  • TPC1 2 3 4
  • Voltage-Dependent Calcium Channel Protein TPC1 3 4
  • Two Pore Calcium Channel Protein 1 3 4
  • KIAA1169 2 4
  • Two-Pore Channel 1, Homolog 3
  • FLJ20612 2
  • TPCN1 5

External Ids for TPCN1 Gene

Previous GeneCards Identifiers for TPCN1 Gene

  • GC12P113441
  • GC12P112071
  • GC12P112121
  • GC12P113660
  • GC12P110671

Summaries for TPCN1 Gene

Entrez Gene Summary for TPCN1 Gene

  • Voltage-gated Ca(2+) and Na+ channels have 4 homologous domains, each containing 6 transmembrane segments, S1 to S6. TPCN1 is similar to these channels, but it has only 2 domains containing S1 to S6 (Ishibashi et al., 2000 [PubMed 10753632]).[supplied by OMIM, Mar 2008]

GeneCards Summary for TPCN1 Gene

TPCN1 (Two Pore Segment Channel 1) is a Protein Coding gene. Diseases associated with TPCN1 include Thyroid Gland Follicular Carcinoma and Thyroid Gland Cancer. Among its related pathways are Calcium signaling pathway 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 identical protein binding and voltage-gated calcium channel activity. An important paralog of this gene is CACNA1B.

UniProtKB/Swiss-Prot Summary for TPCN1 Gene

  • Nicotinic acid adenine dinucleotide phosphate (NAADP) receptor that may function as one of the major voltage-gated Ca(2+) channels (VDCC) across the lysosomal and endosomal membrane.

Gene Wiki entry for TPCN1 Gene

Additional gene information for TPCN1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TPCN1 Gene

Genomics for TPCN1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TPCN1 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 TPCN1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TPCN1

Top Transcription factor binding sites by QIAGEN in the TPCN1 gene promoter:
  • ARP-1
  • CBF-A
  • CBF-B
  • CBF-C
  • CP1A
  • CP1C
  • LUN-1
  • NF-Y
  • NF-YA
  • NF-YB

Genomic Locations for TPCN1 Gene

Genomic Locations for TPCN1 Gene
chr12:113,221,050-113,298,589
(GRCh38/hg38)
Size:
77,540 bases
Orientation:
Plus strand
chr12:113,658,855-113,736,390
(GRCh37/hg19)
Size:
77,536 bases
Orientation:
Plus strand

Genomic View for TPCN1 Gene

Genes around TPCN1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TPCN1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TPCN1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TPCN1 Gene

Proteins for TPCN1 Gene

  • Protein details for TPCN1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9ULQ1-TPC1_HUMAN
    Recommended name:
    Two pore calcium channel protein 1
    Protein Accession:
    Q9ULQ1
    Secondary Accessions:
    • A7E258
    • Q86XS9
    • Q8NC20

    Protein attributes for TPCN1 Gene

    Size:
    816 amino acids
    Molecular mass:
    94147 Da
    Quaternary structure:
    • Dimer.
    SequenceCaution:
    • Sequence=AK057414; Type=Frameshift; Evidence={ECO:0000305}; Sequence=BAA86483.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

    Alternative splice isoforms for TPCN1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TPCN1 Gene

Post-translational modifications for TPCN1 Gene

  • Glycosylation at Asn599, Asn611, and Asn616
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for TPCN1 Gene

Domains & Families for TPCN1 Gene

Gene Families for TPCN1 Gene

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

Protein Domains for TPCN1 Gene

Suggested Antigen Peptide Sequences for TPCN1 Gene

GenScript: Design optimal peptide antigens:
  • TPCN1 protein (A5PKY2_HUMAN)
  • Voltage-dependent calcium channel protein TPC1 (TPC1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9ULQ1

UniProtKB/Swiss-Prot:

TPC1_HUMAN :
  • Each of the two internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position (By similarity).
  • Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. Two pore calcium channel subfamily.
Domain:
  • Each of the two internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position (By similarity).
Family:
  • Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. Two pore calcium channel subfamily.
genes like me logo Genes that share domains with TPCN1: view

Function for TPCN1 Gene

Molecular function for TPCN1 Gene

UniProtKB/Swiss-Prot Function:
Nicotinic acid adenine dinucleotide phosphate (NAADP) receptor that may function as one of the major voltage-gated Ca(2+) channels (VDCC) across the lysosomal and endosomal membrane.

Phenotypes From GWAS Catalog for TPCN1 Gene

Gene Ontology (GO) - Molecular Function for TPCN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005216 ion channel activity IEA --
GO:0005244 voltage-gated ion channel activity IEA --
GO:0005245 voltage-gated calcium channel activity IEA --
GO:0005248 voltage-gated sodium channel activity IEA --
GO:0005262 calcium channel activity IEA --
genes like me logo Genes that share ontologies with TPCN1: view
genes like me logo Genes that share phenotypes with TPCN1: view

Animal Models for TPCN1 Gene

MGI Knock Outs for TPCN1:

Animal Model Products

  • Taconic Biosciences Mouse Models for TPCN1

CRISPR Products

miRNA for TPCN1 Gene

miRTarBase miRNAs that target TPCN1

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TPCN1

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TPCN1 Gene

Localization for TPCN1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TPCN1 Gene

Lysosome membrane. Multi-pass membrane protein. Endosome membrane. Multi-pass membrane protein.

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 TPCN1 gene
Compartment Confidence
endosome 5
lysosome 5
plasma membrane 4
extracellular 2
cytoskeleton 2
mitochondrion 2
nucleus 2
endoplasmic reticulum 2
cytosol 2
peroxisome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for TPCN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005623 cell IEA --
GO:0005764 lysosome TAS 22012985
GO:0005765 lysosomal membrane TAS --
GO:0005768 endosome TAS 22012985
GO:0010008 endosome membrane IBA,IDA 19620632
genes like me logo Genes that share ontologies with TPCN1: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TPCN1 Gene

Pathways & Interactions for TPCN1 Gene

genes like me logo Genes that share pathways with TPCN1: view

Pathways by source for TPCN1 Gene

Gene Ontology (GO) - Biological Process for TPCN1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0006816 calcium ion transport IEA --
GO:0010508 positive regulation of autophagy IDA 22012985
GO:0034220 ion transmembrane transport TAS --
GO:0034765 regulation of ion transmembrane transport IEA --
genes like me logo Genes that share ontologies with TPCN1: view

No data available for SIGNOR curated interactions for TPCN1 Gene

Drugs & Compounds for TPCN1 Gene

(1) Drugs for TPCN1 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Calcium Nutra 6556
genes like me logo Genes that share compounds with TPCN1: view

Transcripts for TPCN1 Gene

mRNA/cDNA for TPCN1 Gene

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

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TPCN1

Alternative Splicing Database (ASD) splice patterns (SP) for TPCN1 Gene

ExUns: 1 ^ 2a · 2b · 2c ^ 3 ^ 4 ^ 5 ^ 6a · 6b · 6c ^ 7a · 7b · 7c ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18a · 18b ^ 19 ^
SP1: -
SP2: - - - -
SP3: - -
SP4: -
SP5: - -
SP6: - - -
SP7:
SP8:
SP9:

ExUns: 20a · 20b ^ 21 ^ 22 ^ 23 ^ 24 ^ 25
SP1: - -
SP2:
SP3:
SP4:
SP5:
SP6:
SP7: -
SP8:
SP9:

Relevant External Links for TPCN1 Gene

GeneLoc Exon Structure for
TPCN1

Expression for TPCN1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TPCN1 Gene

Protein differential expression in normal tissues from HIPED for TPCN1 Gene

This gene is overexpressed in Plasma (36.6) and Heart (7.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for TPCN1 Gene



Protein tissue co-expression partners for TPCN1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TPCN1

SOURCE GeneReport for Unigene cluster for TPCN1 Gene:

Hs.524763

mRNA Expression by UniProt/SwissProt for TPCN1 Gene:

Q9ULQ1-TPC1_HUMAN
Tissue specificity: Highest expression found in the heart and kidney, and lowest expression found in the spleen.

Evidence on tissue expression from TISSUES for TPCN1 Gene

  • Nervous system(4.8)
  • Liver(4.4)
  • Thyroid gland(3.7)
  • Kidney(3.1)
  • Lymph node(2.7)
  • Heart(2.6)
  • Skin(2.6)
  • Muscle(2.5)
  • Intestine(2.4)
  • Lung(2.4)
  • Pancreas(2.3)
  • Blood(2.1)
genes like me logo Genes that share expression patterns with TPCN1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for TPCN1 Gene

Orthologs for TPCN1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for TPCN1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TPCN1 30 31
  • 99.4 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TPCN1 30 31
  • 90.4 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TPCN1 30 31
  • 90.14 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Tpcn1 30 17 31
  • 86.68 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Tpcn1 30
  • 86.6 (n)
Oppossum
(Monodelphis domestica)
Mammalia TPCN1 31
  • 85 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia TPCN1 31
  • 75 (a)
OneToOne
Chicken
(Gallus gallus)
Aves TPCN1 30 31
  • 75.1 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia TPCN1 31
  • 79 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia tpcn1 30
  • 66.83 (n)
Zebrafish
(Danio rerio)
Actinopterygii tpcn1 30 31
  • 69.03 (n)
OneToOne
Species where no ortholog for TPCN1 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)
  • 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)
  • Fruit Fly (Drosophila melanogaster)
  • 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)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for TPCN1 Gene

ENSEMBL:
Gene Tree for TPCN1 (if available)
TreeFam:
Gene Tree for TPCN1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TPCN1: view image

Paralogs for TPCN1 Gene

(15) SIMAP similar genes for TPCN1 Gene using alignment to 14 proteins:

  • TPC1_HUMAN
  • A5PKY2_HUMAN
  • B7Z3R2_HUMAN
  • F8VR74_HUMAN
  • F8VS97_HUMAN
  • F8VV93_HUMAN
  • F8VVY9_HUMAN
  • F8VZZ6_HUMAN
  • F8W0K7_HUMAN
  • F8W0P9_HUMAN
  • F8W1G4_HUMAN
  • F8W1L6_HUMAN
  • H0YHX1_HUMAN
  • H0YIK4_HUMAN
genes like me logo Genes that share paralogs with TPCN1: view

Variants for TPCN1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TPCN1 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
750142 Likely Benign: not provided 113,260,499(+) A/G INTRON_VARIANT
769392 Benign: not provided 113,290,200(+) C/T SYNONYMOUS_VARIANT
773685 Benign: not provided 113,267,845(+) C/T SYNONYMOUS_VARIANT
778664 Benign: not provided 113,278,816(+) G/A SYNONYMOUS_VARIANT
779354 Benign: not provided 113,292,931(+) C/T INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for TPCN1 Gene

Structural Variations from Database of Genomic Variants (DGV) for TPCN1 Gene

Variant ID Type Subtype PubMed ID
esv2226471 CNV deletion 18987734
esv2746378 CNV deletion 23290073
esv3549790 CNV deletion 23714750
esv3630792 CNV gain 21293372
esv3892265 CNV gain 25118596
esv6807 CNV loss 19470904
nsv519540 CNV gain+loss 19592680
nsv560269 CNV loss 21841781

Variation tolerance for TPCN1 Gene

Residual Variation Intolerance Score: 3.92% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.68; 32.15% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TPCN1 Gene

Human Gene Mutation Database (HGMD)
TPCN1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TPCN1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TPCN1 Gene

Disorders for TPCN1 Gene

MalaCards: The human disease database

(7) MalaCards diseases for TPCN1 Gene - From: DISEASES

Disorder Aliases PubMed IDs
thyroid gland follicular carcinoma
  • follicular adenocarcinoma
thyroid gland cancer
  • malignant neoplasm of thyroid gland
thyroid gland medullary carcinoma
  • medullary thyroid carcinoma
mucolipidosis iv
  • ml4
thyroid gland anaplastic carcinoma
  • anaplastic thyroid carcinoma
- elite association - COSMIC cancer census association via MalaCards
Search TPCN1 in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with TPCN1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TPCN1 Gene

Publications for TPCN1 Gene

  1. Essential requirement for two-pore channel 1 in NAADP-mediated calcium signaling. (PMID: 19620632) Brailoiu E … Patel S (The Journal of cell biology 2009) 3 4 23
  2. Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain. (PMID: 10574461) Hirosawa M … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 1999) 2 3 4
  3. NAADP mobilizes calcium from acidic organelles through two-pore channels. (PMID: 19387438) Calcraft PJ … Zhu MX (Nature 2009) 3 4
  4. International Union of Pharmacology. L. Nomenclature and structure-function relationships of CatSper and two-pore channels. (PMID: 16382101) Clapham DE … Garbers DL (Pharmacological reviews 2005) 2 3
  5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4

Products for TPCN1 Gene

Sources for TPCN1 Gene