CALHM1 Gene (Protein Coding)

Calcium Homeostasis Modulator 1

GC10M103454
GIFtS:
33
This gene encodes a calcium channel that plays a role in processing of amyloid-beta precursor protein. A polymorphism at this locus has been reported to be associated with susceptibility to late-onset Alzheimer's disease in some populations, but the pathogenicity of this polymorphism is unclear.[provided by RefSeq, Mar 2010] See more...

Aliases for CALHM1 Gene

Aliases for CALHM1 Gene

  • Calcium Homeostasis Modulator 1 2 3 5
  • Family With Sequence Similarity 26, Member C 2 3
  • Calcium Homeostasis Modulator Protein 1 3 4
  • FAM26C 3 4
  • Protein FAM26C 4
  • CALHM1 5

External Ids for CALHM1 Gene

Previous HGNC Symbols for CALHM1 Gene

  • FAM26C

Previous GeneCards Identifiers for CALHM1 Gene

  • GC10M105204
  • GC10M105213
  • GC10M098843

Summaries for CALHM1 Gene

Entrez Gene Summary for CALHM1 Gene

  • This gene encodes a calcium channel that plays a role in processing of amyloid-beta precursor protein. A polymorphism at this locus has been reported to be associated with susceptibility to late-onset Alzheimer's disease in some populations, but the pathogenicity of this polymorphism is unclear.[provided by RefSeq, Mar 2010]

GeneCards Summary for CALHM1 Gene

CALHM1 (Calcium Homeostasis Modulator 1) is a Protein Coding gene. Diseases associated with CALHM1 include Alzheimer Disease and Creutzfeldt-Jakob Disease. Among its related pathways are Taste transduction. Gene Ontology (GO) annotations related to this gene include identical protein binding and voltage-gated ion channel activity. An important paralog of this gene is CALHM3.

UniProtKB/Swiss-Prot Summary for CALHM1 Gene

  • Pore-forming subunit of a voltage-gated ion channel required for sensory perception of sweet, bitter and umami tastes (By similarity). Specifically present in type II taste bud cells, where it plays a central role in sweet, bitter and umami taste perception by inducing ATP release from the cell, ATP acting as a neurotransmitter to activate afferent neural gustatory pathways (By similarity). Together with CALHM3, forms a fast-activating voltage-gated ATP-release channel in type II taste bud cells (TBCs) (By similarity). Acts both as a voltage-gated and calcium-activated ion channel: mediates neuronal excitability in response to changes in extracellular Ca(2+) concentration (PubMed:22711817, PubMed:23300080). Has poor ion selectivity and forms a wide pore (around 14 Angstroms) that mediates permeation of Ca(2+), Na(+) and K(+), as well as permeation of monovalent anions (PubMed:22711817). Acts as an activator of the ERK1 and ERK2 cascade (PubMed:23345406). Triggers endoplasmic reticulum stress by reducing the calcium content of the endoplasmic reticulum (PubMed:21574960). May indirectly control amyloid precursor protein (APP) proteolysis and aggregated amyloid-beta (Abeta) peptides levels in a Ca(2+) dependent manner (PubMed:18585350).

Additional gene information for CALHM1 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CALHM1 Gene

Genomics for CALHM1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for CALHM1 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
GH10J103459 Promoter/Enhancer 1.2 EPDnew Ensembl ENCODE 600.7 -0.1 -51 0.3 USF1 ZFHX2 EBF1 RFX5 MAZ BHLHE40 EGR2 CALHM1 ENSG00000234699 CALHM3
GH10J103458 Promoter 0.4 Ensembl 600.7 +0.8 799 0.6 GATAD2B CALHM1 ENSG00000234699 CALHM2
GH10J103460 Promoter 0.4 Ensembl 600.7 -0.4 -401 0.2 MAZ CALHM1 ENSG00000234699 CALHM3
GH10J103490 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE dbSUPER 11.9 -33.8 -33816 4.6 SP1 CREB1 ZBTB33 PRDM10 ZNF629 RFX1 BACH1 JUND LARP7 PRDM1 NEURL1 PCGF6 CALHM1 NEURL1-AS1 PDCD11 BORCS7 CALHM3
GH10J103526 Enhancer 1 Ensembl ENCODE 10.3 -68.7 -68728 3.7 ATF7 RFX1 JUND DDX20 ZNF311 SOX6 FOXJ2 CEBPA ZNF639 CEBPB PCGF6 PDCD11 ENSG00000260461 NEURL1 ENSG00000234699 CALHM2 CALHM1 SH3PXD2A NEURL1-AS1 hsa-miR-5095-053
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CALHM1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CALHM1

Top Transcription factor binding sites by QIAGEN in the CALHM1 gene promoter:
  • GR
  • GR-alpha
  • GR-beta
  • HEN1
  • HNF-4alpha1
  • HNF-4alpha2
  • LCR-F1
  • NF-kappaB
  • Pax-5
  • YY1

Genomic Locations for CALHM1 Gene

Genomic Locations for CALHM1 Gene
chr10:103,453,240-103,458,900
(GRCh38/hg38)
Size:
5,661 bases
Orientation:
Minus strand
chr10:105,213,144-105,218,648
(GRCh37/hg19)
Size:
5,505 bases
Orientation:
Minus strand

Genomic View for CALHM1 Gene

Genes around CALHM1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CALHM1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CALHM1 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for CALHM1 Gene

Proteins for CALHM1 Gene

Products:

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  2. Protein
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  • Protein details for CALHM1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8IU99-CAHM1_HUMAN
    Recommended name:
    Calcium homeostasis modulator protein 1
    Protein Accession:
    Q8IU99
    Secondary Accessions:
    • Q5W091

    Protein attributes for CALHM1 Gene

    Size:
    346 amino acids
    Molecular mass:
    38264 Da
    Quaternary structure:
    • Homohexamer. Associates with CALHM3 as a pore-forming subunit in an hetero-hexameric channel complex (By similarity).

neXtProt entry for CALHM1 Gene

Post-translational modifications for CALHM1 Gene

  • Glycosylation at Asn140
  • Modification sites at PhosphoSitePlus

Other Protein References for CALHM1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for CALHM1 Gene

Domains & Families for CALHM1 Gene

Gene Families for CALHM1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted membrane proteins
  • Transporters

Protein Domains for CALHM1 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for CALHM1 Gene

GenScript: Design optimal peptide antigens:
  • Protein FAM26C (CAHM1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8IU99

UniProtKB/Swiss-Prot:

CAHM1_HUMAN :
  • Belongs to the CALHM family.
Family:
  • Belongs to the CALHM family.
genes like me logo Genes that share domains with CALHM1: view

Function for CALHM1 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for CALHM1 Gene

UniProtKB/Swiss-Prot Function:
Pore-forming subunit of a voltage-gated ion channel required for sensory perception of sweet, bitter and umami tastes (By similarity). Specifically present in type II taste bud cells, where it plays a central role in sweet, bitter and umami taste perception by inducing ATP release from the cell, ATP acting as a neurotransmitter to activate afferent neural gustatory pathways (By similarity). Together with CALHM3, forms a fast-activating voltage-gated ATP-release channel in type II taste bud cells (TBCs) (By similarity). Acts both as a voltage-gated and calcium-activated ion channel: mediates neuronal excitability in response to changes in extracellular Ca(2+) concentration (PubMed:22711817, PubMed:23300080). Has poor ion selectivity and forms a wide pore (around 14 Angstroms) that mediates permeation of Ca(2+), Na(+) and K(+), as well as permeation of monovalent anions (PubMed:22711817). Acts as an activator of the ERK1 and ERK2 cascade (PubMed:23345406). Triggers endoplasmic reticulum stress by reducing the calcium content of the endoplasmic reticulum (PubMed:21574960). May indirectly control amyloid precursor protein (APP) proteolysis and aggregated amyloid-beta (Abeta) peptides levels in a Ca(2+) dependent manner (PubMed:18585350).
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by Gd(3+), Ruthenium Red, and Zn(2+) and partially inhibited by 2-aminoethoxydiphenyl borate.

Phenotypes From GWAS Catalog for CALHM1 Gene

Gene Ontology (GO) - Molecular Function for CALHM1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005227 calcium activated cation channel activity IDA 22711817
GO:0005244 voltage-gated ion channel activity IDA 22711817
GO:0005245 voltage-gated calcium channel activity IEA --
GO:0005261 cation channel activity IBA 21873635
GO:0005262 calcium channel activity IEA --
genes like me logo Genes that share ontologies with CALHM1: view
genes like me logo Genes that share phenotypes with CALHM1: view

Animal Models for CALHM1 Gene

MGI Knock Outs for CALHM1:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CALHM1

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for CALHM1 Gene

Localization for CALHM1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CALHM1 Gene

Cell membrane. Multi-pass membrane protein. Endoplasmic reticulum membrane. Multi-pass membrane protein. Basolateral cell membrane. Multi-pass membrane protein. Note=Colocalizes with HSPA5 at the endoplasmic reticulum (PubMed:18585350). Localizes to the basolateral membrane of epithelial cells including taste cells (By similarity). {ECO:0000250 UniProtKB:D3Z291, ECO:0000269 PubMed:18585350}.

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 CALHM1 gene
Compartment Confidence
plasma membrane 5
endoplasmic reticulum 4
extracellular 2
cytosol 2
golgi apparatus 2
cytoskeleton 1
mitochondrion 1
nucleus 1
endosome 1
lysosome 1

Gene Ontology (GO) - Cellular Components for CALHM1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IEA --
GO:0005789 endoplasmic reticulum membrane IEA --
GO:0005886 plasma membrane IEA --
GO:0005887 integral component of plasma membrane IBA,IDA 22711817
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with CALHM1: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for CALHM1 Gene

Pathways & Interactions for CALHM1 Gene

PathCards logo

SuperPathways for CALHM1 Gene

SuperPathway Contained pathways
1 Taste transduction
Taste transduction
.35
genes like me logo Genes that share pathways with CALHM1: view

Pathways by source for CALHM1 Gene

1 KEGG pathway for CALHM1 Gene

Interacting Proteins for CALHM1 Gene

STRING Interaction Network Preview (showing top 4 STRING interactants - click image to see details)
STRING Interaction Network
Selected Interacting proteins: Q8IU99-CAHM1_HUMAN ENSP00000329926 for CALHM1 Gene via UniProtKB STRING IID

GPS-Prot Interaction Network for CALHM1

Gene Ontology (GO) - Biological Process for CALHM1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0006812 cation transport IDA 22711817
GO:0006816 calcium ion transport IEA --
GO:0015867 ATP transport IEA,ISS --
GO:0034765 regulation of ion transmembrane transport IDA 23300080
genes like me logo Genes that share ontologies with CALHM1: view

No data available for SIGNOR curated interactions for CALHM1 Gene

Drugs & Compounds for CALHM1 Gene

Products:

  1. Drug
No Compound Related Data Available

Transcripts for CALHM1 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for CALHM1 Gene

1 REFSEQ mRNAs :
2 NCBI additional mRNA sequence :
1 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 CALHM1

Alternative Splicing Database (ASD) splice patterns (SP) for CALHM1 Gene

No ASD Table

Relevant External Links for CALHM1 Gene

GeneLoc Exon Structure for
CALHM1

Expression for CALHM1 Gene

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  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CALHM1 Gene

mRNA expression in normal human tissues for CALHM1 Gene
mRNA expression by GTEx for CALHM1 Gene

mRNA differential expression in normal tissues according to GTEx for CALHM1 Gene

This gene is overexpressed in Brain - Cortex (x9.6), Brain - Frontal Cortex (BA9) (x8.4), and Brain - Anterior cingulate cortex (BA24) (x7.0).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CALHM1

SOURCE GeneReport for Unigene cluster for CALHM1 Gene:

Hs.680365

mRNA Expression by UniProt/SwissProt for CALHM1 Gene:

Q8IU99-CAHM1_HUMAN
Tissue specificity: Predominantly expressed in adult brain. Detected also in retinoic acid-differentiated SH-SY5Y cells. Specifically expressed in circumvallate taste bud cells.

Evidence on tissue expression from TISSUES for CALHM1 Gene

  • Nervous system(4.8)
genes like me logo Genes that share expression patterns with CALHM1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for CALHM1 Gene

Orthologs for CALHM1 Gene

This gene was present in the common ancestor of animals.

Orthologs for CALHM1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia CALHM1 30 31
  • 99.42 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia CALHM1 30 31
  • 90.7 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia CALHM1 30 31
  • 90.31 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Calhm1 30
  • 85.95 (n)
Mouse
(Mus musculus)
 Mammalia Calhm1 30 17 31
  • 85.56 (n)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia CALHM1 31
  • 85 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia CALHM1 31
  • 81 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves CALHM1 30 31
  • 74.17 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia CALHM1 31
  • 74 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia calhm1 30
  • 66.67 (n)
Zebrafish
(Danio rerio)
 Actinopterygii LOC101887127 30
  • 64.59 (n)
CALHM1 (1 of 2) 31
  • 58 (a)
 OneToMany
calhm1 31
  • 56 (a)
 OneToMany
Worm
(Caenorhabditis elegans)
 Secernentea clhm-1 31
  • 16 (a)
 OneToMany
Sea Squirt
(Ciona savignyi)
 Ascidiacea -- 31
  • 11 (a)
 OneToMany
Species where no ortholog for CALHM1 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 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 CALHM1 Gene

ENSEMBL:
Gene Tree for CALHM1 (if available)
TreeFam:
Gene Tree for CALHM1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CALHM1: view image

Paralogs for CALHM1 Gene

Paralogs for CALHM1 Gene

(2) SIMAP similar genes for CALHM1 Gene using alignment to 1 proteins:

  • CAHM1_HUMAN
genes like me logo Genes that share paralogs with CALHM1: view

Variants for CALHM1 Gene

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  1. SNP Genotyping and Copy Number Assay

Polymorphic Variants from UniProtKB/Swiss-Prot for CALHM1 Gene

CAHM1_HUMAN-Q8IU99
Leu-86 causes a dysregulation of Ca(2+) homeostasis and amyloid precursor protein (APP) metabolism and has been suggested to be a risk factor for the development of Alzheimer disease (PubMed:18585350, PubMed:20061624, PubMed:20164592). However, this association with Alzheimer disease could not be confirmed in a number of studies performed in different populations (PubMed:19472444, PubMed:19070563, PubMed:19191331, PubMed:19191332, PubMed:19545933, PubMed:19655363, PubMed:21378601). According to a meta-analysis study, Leu-86 is likely not a genetic determinant of Alzheimer disease but may modulate age of onset by interacting with the effect of the APOE*4 allele of the APOE gene (PubMed:20847397).

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CALHM1 Gene

SNP ID Clinical significance and condition Chr 10 pos Variation AA Info Type
781217 Benign: not provided 103,458,295(-) C/T MISSENSE_VARIANT
rs371900329 Likely Pathogenic: not provided 103,458,291(-) C/T MISSENSE_VARIANT
rs2986017 - p.Leu86Pro

Additional dbSNP identifiers (rs#s) for CALHM1 Gene

Structural Variations from Database of Genomic Variants (DGV) for CALHM1 Gene

Variant ID Type Subtype PubMed ID
dgv280e212 CNV gain 25503493
dgv965n100 CNV gain 25217958
dgv966n100 CNV gain 25217958
esv3577694 CNV gain 25503493
esv3624413 CNV gain 21293372
esv3624414 CNV gain 21293372
nsv437692 CNV loss 16327808
nsv518987 CNV loss 19592680
nsv524966 CNV loss 19592680
nsv552060 CNV loss 21841781

Variation tolerance for CALHM1 Gene

Residual Variation Intolerance Score: 93.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.46; 54.95% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CALHM1 Gene

Human Gene Mutation Database (HGMD)
CALHM1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CALHM1

Disorders for CALHM1 Gene

MalaCards: The human disease database

(2) MalaCards diseases for CALHM1 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
alzheimer disease
  • ad
creutzfeldt-jakob disease
  • cjd
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for CALHM1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with CALHM1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CALHM1 Gene

Publications for CALHM1 Gene

  1. CALHM1 variant is not associated with Alzheimer's disease among Asians. (PMID: 19545933) Tan EK … Zhao Y (Neurobiology of aging 2011) 3 4 41
  2. The P86L common allele of CALHM1 does not influence risk for Alzheimer disease in Japanese cohorts. (PMID: 19655363) Inoue K … Goto YI (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2010) 3 4 41
  3. CALHM1 P86L polymorphism is a risk factor for Alzheimer's disease in the Chinese population. (PMID: 20061624) Cui PJ … Chen SD (Journal of Alzheimer's disease : JAD 2010) 3 4 41
  4. No association between CALHM1 and risk for Alzheimer dementia in a Belgian population. (PMID: 19191332) Sleegers K … Van Broeckhoven C (Human mutation 2009) 3 4 41
  5. CALHM1 polymorphism is not associated with late-onset Alzheimer disease. (PMID: 19472444) Beecham GW … Pericak-Vance MA (Annals of human genetics 2009) 3 4 41

ExternalLinks

View latest publications for CALHM1 gene in Mastermind

Products for CALHM1 Gene

  • Signalway Proteins for CALHM1

Sources for CALHM1 Gene