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

ENSG00000092439 ∙ NCBI:54822 ∙ OMIM:605692 ∙ HGNC:17994 ∙ Uniprot:Q96QT4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant macrothrombocytopenia (Supportive), mode of inheritance: AD
• amyotrophic lateral sclerosis-parkinsonism-dementia complex (Limited), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRPM7 gene.

• 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	6	9
missense	2		75	6	2	85
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel					1	1
splice donor/acceptor (+/-2bp)				1		1
splice region			1	1	4	6
non coding			2		23	25
Total	2	0	79	10	32

Variants in TRPM7

This is a list of pathogenic ClinVar variants found in the TRPM7 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-50561374-A-G			Benign (Nov 12, 2018)
15-50561691-C-T		not specified	Uncertain significance (Oct 14, 2021)
15-50561743-T-C		not specified	Uncertain significance (Apr 17, 2024)
15-50561761-C-T		not specified	Uncertain significance (Sep 14, 2022)
15-50569898-A-G			Uncertain significance (May 13, 2023)
15-50569947-T-C		not specified	Uncertain significance (May 07, 2024)
15-50570100-T-C			Benign (Dec 01, 2023)
15-50570160-A-G		TRPM7-related disorder	Likely benign (May 01, 2023)
15-50574314-G-A		TRPM7-related disorder	Benign (Dec 05, 2019)
15-50574361-T-C		not specified	Uncertain significance (Apr 17, 2024)
15-50574426-A-G		not specified	Uncertain significance (Jan 03, 2024)
15-50574447-G-A			Uncertain significance (May 01, 2024)
15-50574458-C-T			Likely benign (May 23, 2018)
15-50574885-G-A			Benign (Nov 12, 2018)
15-50574892-C-T		TRPM7-related disorder	Benign (Nov 14, 2019)
15-50574930-G-T			Likely benign (Jan 31, 2018)
15-50574943-T-C		Amyotrophic lateral sclerosis-parkinsonism-dementia complex	Uncertain significance (Aug 31, 2021)
15-50574945-C-T		TRPM7-related disorder	Benign (Dec 11, 2023)
15-50575024-T-C		not specified	Uncertain significance (Sep 23, 2023)
15-50575093-T-C		not specified	Likely benign (Nov 12, 2021)
15-50575096-G-A			Uncertain significance (Oct 19, 2022)
15-50578648-T-C		not specified	Uncertain significance (Sep 14, 2022)
15-50580874-A-C			Uncertain significance (-)
15-50580875-T-C		not specified	Uncertain significance (Nov 09, 2021)
15-50583071-T-C		not specified	Uncertain significance (Jun 01, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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