This gene encodes a putative cation-selective ion channel with two repeats of a six-transmembrane-domain. The protein localizes to lysosomal membranes and enables nicotinic acid adenine dinucleotide phosphate (NAADP) -induced calcium ion release from lysosome-related stores. This ubiquitously expressed gene has elevated expression in liver and kidney. Two common nonsynonymous S... See more...

Aliases for TPCN2 Gene

Aliases for TPCN2 Gene

  • Two Pore Segment Channel 2 2 3 5
  • Voltage-Dependent Calcium Channel Protein TPC2 3 4
  • Two Pore Calcium Channel Protein 2 3 4
  • TPC2 3 4
  • SHEP10 3

External Ids for TPCN2 Gene

Previous GeneCards Identifiers for TPCN2 Gene

  • GC11P068591
  • GC11P068572
  • GC11P068816
  • GC11P065155

Summaries for TPCN2 Gene

Entrez Gene Summary for TPCN2 Gene

  • This gene encodes a putative cation-selective ion channel with two repeats of a six-transmembrane-domain. The protein localizes to lysosomal membranes and enables nicotinic acid adenine dinucleotide phosphate (NAADP) -induced calcium ion release from lysosome-related stores. This ubiquitously expressed gene has elevated expression in liver and kidney. Two common nonsynonymous SNPs in this gene strongly associate with blond versus brown hair pigmentation.[provided by RefSeq, Dec 2009]

GeneCards Summary for TPCN2 Gene

TPCN2 (Two Pore Segment Channel 2) is a Protein Coding gene. Diseases associated with TPCN2 include Skin/Hair/Eye Pigmentation, Variation In, 10 and Deafness, Autosomal Recessive 63. Among its related pathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Ion channel transport. Gene Ontology (GO) annotations related to this gene include identical protein binding and ion channel activity. An important paralog of this gene is ENSG00000287725.

UniProtKB/Swiss-Prot Summary for TPCN2 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 membrane. May be involved in smooth muscle contraction.

Gene Wiki entry for TPCN2 Gene

Additional gene information for TPCN2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TPCN2 Gene

Genomics for TPCN2 Gene

GeneHancer (GH) Regulatory Elements for TPCN2 Gene

Promoters and enhancers for TPCN2 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 TPCN2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the TPCN2 gene promoter:
  • AML1a
  • Arnt
  • CUTL1
  • Ik-1
  • Ik-2
  • MAZR
  • NF-kappaB
  • NF-kappaB1
  • Roaz

Genomic Locations for TPCN2 Gene

Genomic Locations for TPCN2 Gene
chr11:69,048,882-69,160,413
(GRCh38/hg38)
Size:
111,532 bases
Orientation:
Plus strand
chr11:68,816,350-68,858,072
(GRCh37/hg19)
Size:
41,723 bases
Orientation:
Plus strand

Genomic View for TPCN2 Gene

Genes around TPCN2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TPCN2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TPCN2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TPCN2 Gene

Proteins for TPCN2 Gene

  • Protein details for TPCN2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8NHX9-TPC2_HUMAN
    Recommended name:
    Two pore calcium channel protein 2
    Protein Accession:
    Q8NHX9
    Secondary Accessions:
    • Q9NT82

    Protein attributes for TPCN2 Gene

    Size:
    752 amino acids
    Molecular mass:
    85243 Da
    Quaternary structure:
    • Homodimer (By similarity). Interacts with LRRK2 (PubMed:22012985). Interacts with HAX1 (PubMed:24188827).

    Three dimensional structures from OCA and Proteopedia for TPCN2 Gene

neXtProt entry for TPCN2 Gene

Post-translational modifications for TPCN2 Gene

Other Protein References for TPCN2 Gene

No data available for DME Specific Peptides for TPCN2 Gene

Domains & Families for TPCN2 Gene

Gene Families for TPCN2 Gene

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

Protein Domains for TPCN2 Gene

Suggested Antigen Peptide Sequences for TPCN2 Gene

GenScript: Design optimal peptide antigens:
  • Voltage-dependent calcium channel protein TPC2 (TPC2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8NHX9

UniProtKB/Swiss-Prot:

TPC2_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 TPCN2: view

Function for TPCN2 Gene

Molecular function for TPCN2 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 membrane. May be involved in smooth muscle contraction.

Phenotypes From GWAS Catalog for TPCN2 Gene

Gene Ontology (GO) - Molecular Function for TPCN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005244 voltage-gated ion channel activity IEA --
GO:0005245 voltage-gated calcium channel activity IEA,ISS --
GO:0005262 calcium channel activity IEA --
GO:0005515 protein binding IPI 21903581
GO:0019901 protein kinase binding IPI 22012985
genes like me logo Genes that share ontologies with TPCN2: view
genes like me logo Genes that share phenotypes with TPCN2: view

Animal Models for TPCN2 Gene

MGI Knock Outs for TPCN2:

Animal Model Products

  • Taconic Biosciences Mouse Models for TPCN2

CRISPR Products

miRNA for TPCN2 Gene

miRTarBase miRNAs that target TPCN2

Clone Products

  • Addgene plasmids for TPCN2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TPCN2 Gene

Localization for TPCN2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TPCN2 Gene

Lysosome membrane; Multi-pass membrane protein. Note=Only the acidic lysosomal fraction is sensitive to NAADP. {ECO:0000250}.

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 TPCN2 gene
Compartment Confidence
endosome 5
lysosome 5
plasma membrane 3
nucleus 2
endoplasmic reticulum 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for TPCN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005764 lysosome IDA 22012985
GO:0005765 lysosomal membrane IEA,TAS --
GO:0010008 endosome membrane IDA 19620632
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with TPCN2: view

Pathways & Interactions for TPCN2 Gene

genes like me logo Genes that share pathways with TPCN2: view

Pathways by source for TPCN2 Gene

Gene Ontology (GO) - Biological Process for TPCN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0006816 calcium ion transport IEA --
GO:0006874 cellular calcium ion homeostasis IDA 19387438
GO:0006939 smooth muscle contraction ISS --
GO:0007040 lysosome organization IGI 25416817
genes like me logo Genes that share ontologies with TPCN2: view

No data available for SIGNOR curated interactions for TPCN2 Gene

Drugs & Compounds for TPCN2 Gene

(1) Drugs for TPCN2 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Calcium Approved Nutra 7773
genes like me logo Genes that share compounds with TPCN2: view

Transcripts for TPCN2 Gene

mRNA/cDNA for TPCN2 Gene

CRISPR Products

Clone Products

  • Addgene plasmids for TPCN2

Alternative Splicing Database (ASD) splice patterns (SP) for TPCN2 Gene

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

ExUns: 17b ^ 18 ^ 19 ^ 20 ^ 21a · 21b ^ 22 ^ 23 ^ 24 ^ 25a · 25b
SP1: -
SP2: - - -
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:

Relevant External Links for TPCN2 Gene

GeneLoc Exon Structure for
TPCN2
ECgene alternative splicing isoforms for
TPCN2

Expression for TPCN2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for TPCN2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for TPCN2 Gene

This gene is overexpressed in Prostate (48.2), Monocytes (11.6), and Stomach (9.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for TPCN2 Gene



Protein tissue co-expression partners for TPCN2 Gene

NURSA nuclear receptor signaling pathways regulating expression of TPCN2 Gene:

TPCN2

SOURCE GeneReport for Unigene cluster for TPCN2 Gene:

Hs.131851

mRNA Expression by UniProt/SwissProt for TPCN2 Gene:

Q8NHX9-TPC2_HUMAN
Tissue specificity: Widely expressed. Expressed at high level in liver and kidney.

Evidence on tissue expression from TISSUES for TPCN2 Gene

  • Blood(4.1)
genes like me logo Genes that share expression patterns with TPCN2: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for TPCN2 Gene

Orthologs for TPCN2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for TPCN2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TPCN2 33 32
  • 97.7 (n)
OneToOne
dog
(Canis familiaris)
Mammalia TPCN2 33 32
  • 84.82 (n)
OneToOne
cow
(Bos Taurus)
Mammalia TPCN2 33 32
  • 83.2 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Tpcn2 17 33 32
  • 79.78 (n)
rat
(Rattus norvegicus)
Mammalia Tpcn2 32
  • 79.62 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia TPCN2 33
  • 70 (a)
OneToOne
chicken
(Gallus gallus)
Aves TPCN2 33 32
  • 68.54 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TPCN2 33
  • 68 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia tpcn2 32
  • 66.15 (n)
zebrafish
(Danio rerio)
Actinopterygii tpcn2 33 32
  • 61.14 (n)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea -- 33
  • 39 (a)
OneToOne
Species where no ortholog for TPCN2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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)
  • oppossum (Monodelphis domestica)
  • 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 TPCN2 Gene

ENSEMBL:
Gene Tree for TPCN2 (if available)
TreeFam:
Gene Tree for TPCN2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TPCN2: view image

Paralogs for TPCN2 Gene

Variants for TPCN2 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for TPCN2 Gene

TPC2_HUMAN-Q8NHX9
Genetic variants in TPCN2 define the skin/hair/eye pigmentation variation locus 10 (SHEP10) [MIM:612267]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair.

Sequence variations from dbSNP and Humsavar for TPCN2 Gene

SNP ID Clin Chr 11 pos Variation AA Info Type
rs35264875 association, Skin/hair/eye pigmentation, variation in, 10, - 69,078,931(+) A/C/T coding_sequence_variant, missense_variant
rs3829241 association, Skin/hair/eye pigmentation, variation in, 10, - 69,087,895(+) G/A coding_sequence_variant, missense_variant
rs1000066459 -- 69,059,823(+) C/T intron_variant
rs1000092536 -- 69,084,478(+) C/A/T intron_variant
rs1000192593 -- 69,082,324(+) A/G intron_variant

Structural Variations from Database of Genomic Variants (DGV) for TPCN2 Gene

Variant ID Type Subtype PubMed ID
dgv1987n54 CNV loss 21841781
dgv1988n54 CNV loss 21841781
dgv1989n54 CNV gain+loss 21841781
dgv226n67 CNV gain 20364138
esv1002444 CNV insertion 20482838
esv1163200 CNV insertion 17803354
esv1281432 CNV insertion 17803354
esv1356674 CNV insertion 17803354
esv1429725 CNV deletion 17803354
esv1613113 CNV insertion 17803354
esv1661230 CNV insertion 17803354
esv1755381 CNV insertion 17803354
esv22030 CNV loss 19812545
esv26530 CNV loss 19812545
esv2741565 CNV deletion 23290073
esv2743408 CNV deletion 23290073
esv2744672 CNV deletion 23290073
esv2744673 CNV deletion 23290073
esv2744675 CNV deletion 23290073
esv2744676 CNV deletion 23290073
esv2744677 CNV deletion 23290073
esv2744678 CNV deletion 23290073
esv2744679 CNV deletion 23290073
esv998682 CNV deletion 20482838
nsv1130658 CNV deletion 24896259
nsv1138046 CNV deletion 24896259
nsv468619 CNV loss 19166990
nsv468620 CNV loss 19166990
nsv469967 CNV loss 18288195
nsv521595 CNV gain 19592680
nsv555299 CNV loss 21841781
nsv555300 CNV loss 21841781
nsv555301 CNV loss 21841781
nsv555302 CNV gain 21841781
nsv555305 CNV gain+loss 21841781
nsv555317 CNV gain+loss 21841781
nsv825970 CNV gain 20364138
nsv832196 CNV loss 17160897

Variation tolerance for TPCN2 Gene

Residual Variation Intolerance Score: 84.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.96; 87.29% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TPCN2 Gene

Human Gene Mutation Database (HGMD)
TPCN2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TPCN2

SNP Genotyping and Copy Number Assay Products

Disorders for TPCN2 Gene

MalaCards: The human disease database

(4) MalaCards diseases for TPCN2 Gene - From: HGMD, OMIM, GTR, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search TPCN2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for TPCN2

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 TPCN2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TPCN2 Gene

Publications for TPCN2 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 56
  2. Two newly identified genetic determinants of pigmentation in Europeans. (PMID: 18488028) Sulem P … Stefansson K (Nature genetics 2008) 3 4 43 56
  3. Hax-1 identified as a two-pore channel (TPC)-binding protein. (PMID: 24188827) Lam AK … Zissimopoulos S (FEBS letters 2013) 3 4 56
  4. Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP. (PMID: 22012985) Gómez-Suaga P … Hilfiker S (Human molecular genetics 2012) 3 4 56
  5. Web-based, participant-driven studies yield novel genetic associations for common traits. (PMID: 20585627) Eriksson N … Mountain J (PLoS genetics 2010) 3 43 56

Products for TPCN2 Gene

Sources for TPCN2 Gene