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 (Strong), mode of inheritance: AR
• intestinal hypomagnesemia 1 (Supportive), 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 (419 variants)
• Intestinal_hypomagnesemia_1 (358 variants)
• Inborn_genetic_diseases (231 variants)
• TRPM6-related_disorder (16 variants)
• not_specified (13 variants)
• Hypomagnesemia (2 variants)
• Rod-cone_dystrophy (1 variants)
• Abnormality_of_the_eye (1 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			24	135	4	163
missense	3	2	412	32	5	454
nonsense	11	11	2			24
start loss						0
frameshift	13	15	3			31
splice donor/acceptor (+/-2bp)	5	7	2			14
Total	32	35	443	167	9

Highest pathogenic variant AF is 0.000019707022

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
		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

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

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