TRPM6

transient receptor potential cation channel subfamily M member 6, the group of Transient receptor potential cation channels

Basic information

Region (hg38): 9:74722495-74888094

Previous symbols: [ "HOMG", "HSH" ]

Links

ENSG00000119121

∙ NCBI:140803 ∙ OMIM:607009 ∙ HGNC:17995 ∙ Uniprot:Q9BX84 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

intestinal hypomagnesemia 1 (Supportive), mode of inheritance: AR
intestinal hypomagnesemia 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypomagnesemia 1, intestinal	AR	Gastrointestinal	Individuals typically present in infancy with manifestations of electrolyte imbalances (hypomagnesemia and consequent hypocalcemia) , which may result in death or severe neurologic impairment such that immediate magnesium administration can be effective in the acute period, though individuals require chronic high-dose oral magnesium supplementation	Gastrointestinal	12032568; 12032570; 23942199

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRPM6 gene.

not_provided (376 variants)
Intestinal_hypomagnesemia_1 (353 variants)
Inborn_genetic_diseases (206 variants)
TRPM6-related_disorder (16 variants)
not_specified (4 variants)
Hypomagnesemia (4 variants)
Rod-cone_dystrophy (3 variants)
Abnormality_of_the_eye (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRPM6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017662.5. 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			25 clinvar	115 clinvar	4 clinvar	144
missense	3 clinvar	2 clinvar	387 clinvar	30 clinvar	5 clinvar	427
nonsense	8 clinvar	11 clinvar	1 clinvar			20
start loss						0
frameshift	11 clinvar	15 clinvar	3 clinvar			29
splice donor/acceptor (+/-2bp)	5 clinvar	6 clinvar	1 clinvar			12
Total	27	34	417	145	9

Highest pathogenic variant AF is 0.000019707

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRPM6	protein_coding	protein_coding	ENST00000360774	39	165600

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.72e-10	1.00	125685	0	63	125748	0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.61	885	1.03e+3	0.859	0.0000550	13362
Missense in Polyphen		244	327.76	0.74444		4428
Synonymous	-1.40	415	380	1.09	0.0000213	3737
Loss of Function	6.37	38	110	0.345	0.00000593	1315

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000449	0.000448
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000317	0.000308
Middle Eastern	0.000218	0.000217
South Asian	0.000327	0.000294
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Essential ion channel and serine/threonine-protein kinase. Crucial for magnesium homeostasis. Has an important role in epithelial magnesium transport and in the active magnesium absorption in the gut and kidney. Isoforms of the type M6-kinase lack the ion channel region.;
Pathway: Mineral absorption - Homo sapiens (human);Stimuli-sensing channels;Ion channel transport;Transport of small molecules;TRP channels (Consensus)

Recessive Scores

pRec: 0.174

Intolerance Scores

loftool: 0.660
rvis_EVS: -0.58
rvis_percentile_EVS: 18.72

Haploinsufficiency Scores

pHI: 0.142
hipred: Y
hipred_score: 0.663
ghis: 0.434

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.100

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Trpm6
Phenotype: embryo phenotype; reproductive 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); 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); skeleton phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; craniofacial phenotype;

Gene ontology

Biological process: protein phosphorylation;response to toxic substance;protein tetramerization;calcium ion transmembrane transport
Cellular component: plasma membrane;integral component of membrane;apical plasma membrane;brush border membrane
Molecular function: protein serine/threonine kinase activity;calcium channel activity;protein binding;ATP binding;metal ion binding