CALHM1
protein-codingcalcium homeostasis modulator 1, the group of Calcium homeostasis modulators
Gene summary
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]
- FAM26C
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CALHM1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001001412.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 1 | 70 | 1 | 72 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 1 | 70 | 0 | 1 | 72 |
Highest pathogenic variant AF is 0.00007072232
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001001412.3 | 2 | MANE Select | |
| Ensembl | ENSP00000329926.6 | 2 | MANE Select |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Taste transduction - Homo sapiens (human)
Biological Process
- cation transport
- ATP transport
- regulation of ion transmembrane transport
- sensory perception of bitter taste
- sensory perception of sweet taste
Molecular Function
- calcium activated cation channel activity
- voltage-gated ion channel activity
- voltage-gated calcium channel activity
- identical protein binding
Cellular Component
- endoplasmic reticulum membrane
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000329905
- Coding exons
- 2
- Length
- 5502
- Individuals with no LoFs
- 125483
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 246
- Defined
- 125730
- p
- 0.000983
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.166 | 255 | 248 | 1.03 | 0.0000176 | 2224 |
| Missense (PolyPhen) | 97 | 99.816 | 0.97179 | 1023 | ||
| Synonymous | -0.737 | 127 | 117 | 1.09 | 0.00000925 | 751 |
| Loss of Function | 0.487 | 8 | 9.63 | 0.831 | 4.99e-7 | 97 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00063 | 0.00062 | rare |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.0048 | 0.0048 | notable |
| European (Non-Finnish) | 0.00021 | 0.00018 | rare |
| South Asian | 0.0033 | 0.0033 | notable |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Pore-forming subunit of a voltage-gated ion channel required for sensory perception of sweet, bitter and umami tastes. 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. Acts both as a voltage-gated and calcium-activated ion channel: mediates neuronal excitability in response to changes in extracellular Ca(2+) concentration. 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. Acts as an activator of the ERK1 and ERK2 cascade. Triggers endoplasmic reticulum stress by reducing the calcium content of the endoplasmic reticulum. May indirectly control amyloid precursor protein (APP) proteolysis and aggregated amyloid-beta (Abeta) peptides levels in a Ca(2+) dependent manner. {ECO:0000269|PubMed:18585350, ECO:0000269|PubMed:21574960, ECO:0000269|PubMed:22711817, ECO:0000269|PubMed:23300080, ECO:0000269|PubMed:23345406}.;
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- LoFtool
- 0.659
- RVIS EVS
- -0.11
- RVIS percentile EVS
- 45.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.205
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |