TRPM7
transient receptor potential cation channel subfamily M member 7, the group of Transient receptor potential cation channels
Basic information
Region (hg38): 15:50552473-50686797
Links
Phenotypes
GenCC
Source:
- autosomal dominant macrothrombocytopenia (Supportive), mode of inheritance: AD
- amyotrophic lateral sclerosis-parkinsonism-dementia complex (Limited), mode of inheritance: Unknown
- hypomagnesemia, seizures, and intellectual disability (Moderate), mode of inheritance: AD
- macrothrombocytopenia, isolated (Limited), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (180 variants)
- not_provided (53 variants)
- TRPM7-related_disorder (12 variants)
- Amyotrophic_lateral_sclerosis-parkinsonism-dementia_complex (8 variants)
- Intestinal_hypomagnesemia_1 (2 variants)
- See_cases (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRPM7 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017672.6. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 8 | |||||
| missense | 203 | 11 | 219 | |||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 2 | |||||
| splice donor/acceptor (+/-2bp) | 4 | |||||
| Total | 4 | 0 | 209 | 17 | 5 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TRPM7 | protein_coding | protein_coding | ENST00000313478 | 39 | 134343 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 5.21e-16 | 1.00 | 124693 | 0 | 101 | 124794 | 0.000405 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.23 | 756 | 950 | 0.796 | 0.0000460 | 12332 |
| Missense in Polyphen | 197 | 319.83 | 0.61594 | 4114 | ||
| Synonymous | -0.474 | 326 | 315 | 1.03 | 0.0000154 | 3399 |
| Loss of Function | 5.29 | 44 | 101 | 0.434 | 0.00000543 | 1256 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000725 | 0.000701 |
| Ashkenazi Jewish | 0.000202 | 0.000199 |
| East Asian | 0.000816 | 0.000779 |
| Finnish | 0.000420 | 0.000417 |
| European (Non-Finnish) | 0.000403 | 0.000397 |
| Middle Eastern | 0.000816 | 0.000779 |
| South Asian | 0.000501 | 0.000490 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Essential ion channel and serine/threonine-protein kinase. Divalent cation channel permeable to calcium and magnesium. Has a central role in magnesium ion homeostasis and in the regulation of anoxic neuronal cell death. Involved in TNF- induced necroptosis downstream of MLKL by mediating calcium influx. The kinase activity is essential for the channel function. May be involved in a fundamental process that adjusts plasma membrane divalent cation fluxes according to the metabolic state of the cell. Phosphorylates annexin A1 (ANXA1). {ECO:0000269|PubMed:12887921, ECO:0000269|PubMed:15485879, ECO:0000269|PubMed:24316671}.;
- Disease
- DISEASE: Amyotrophic lateral sclerosis-parkinsonism/dementia complex 1 (ALS-PDC1) [MIM:105500]: A neurodegenerative disorder characterized by chronic, progressive and uniformly fatal amyotrophic lateral sclerosis and parkinsonism-dementia. Both diseases are known to occur in the same kindred, the same sibship and even the same individual. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
- Pathway
- Necroptosis - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Mineral absorption - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Stimuli-sensing channels;Ion channel transport;Transport of small molecules;TRP channels
(Consensus)
Recessive Scores
- pRec
- 0.147
Intolerance Scores
- loftool
- 0.797
- rvis_EVS
- -0.83
- rvis_percentile_EVS
- 11.49
Haploinsufficiency Scores
- pHI
- 0.283
- hipred
- Y
- hipred_score
- 0.706
- ghis
- 0.596
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.878
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Trpm7
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); pigmentation phenotype; endocrine/exocrine gland phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Zebrafish Information Network
- Gene name
- trpm7
- Affected structure
- dopaminergic neuron
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- cellular magnesium ion homeostasis;calcium-dependent cell-matrix adhesion;actomyosin structure organization;protein autophosphorylation;protein tetramerization;necroptotic process;calcium ion transmembrane transport
- Cellular component
- ruffle;plasma membrane;integral component of membrane
- Molecular function
- actin binding;protein serine/threonine kinase activity;calcium channel activity;ATP binding;myosin binding;metal ion binding