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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TRPM6
transient receptor potential cation channel subfamily M member 6
Chromosome 9 · 9q21.13
NCBI Gene: 140803Ensembl: ENSG00000119121.23HGNC: HGNC:17995UniProt: Q9BX84
71PubMed Papers
21Diseases
0Drugs
67Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelKinaseTransporter
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
response to toxic substancemagnesium ion transmembrane transportcalcium ion transmembrane transportprotein serine/threonine kinase activityintestinal hypomagnesemia 1Primary hypomagnesemia with secondary hypocalcemiagenetic disordernephrolithiasis
✦AI Summary

TRPM6 is a bifunctional protein comprising a TRP cation channel segment covalently linked to an α-type serine/threonine protein kinase 1. The channel primarily functions in magnesium homeostasis, facilitating transcellular Mg²⁺ absorption in the colon through TRPM6/7 complexes and apical Mg²⁺ uptake in the distal convoluted tubule of the kidney, where it is hormonally regulated by insulin and epidermal growth factor 2. TRPM6 is expressed in intestinal and renal epithelial cells and plays a central role in systemic Mg²⁺ homeostasis 1. Loss-of-function mutations in TRPM6 cause hypomagnesemia with secondary hypocalcemia (HSH), demonstrating its critical role in magnesium regulation 13. In contrast to human mutations, Trpm6 null mice show prenatal developmental delays, neural tube defects, and prenatal death, suggesting additional developmental functions 1. The channel belongs to the TRPM family of melastatin-related transient receptor potential channels, which are highly permeable to divalent cations including Ca²⁺, Mg²⁺, and Zn²⁺ 4. Clinically, TRPM6 mutations represent one of several hereditary forms of hypomagnesemia that have been identified 3.

Sources cited
1
TRPM6 is a bifunctional protein with TRP channel and kinase domains, expressed in intestinal and renal epithelial cells, and mutations cause hypomagnesemia with secondary hypocalcemia
PMID: 24756719
2
TRPM6/7 complexes facilitate transcellular Mg²⁺ absorption in colon and apical Mg²⁺ uptake in distal convoluted tubule, regulated by insulin and epidermal growth factor
PMID: 38871680
3
TRPM6 mutations are among hereditary forms of hypomagnesemia that have been identified
PMID: 25540137
4
TRPM channels including TRPM6 are highly permeable to divalent cations like Ca²⁺, Mg²⁺, and Zn²⁺
PMID: 37853091
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ21
intestinal hypomagnesemia 1Open Targets
0.78Strong
Primary hypomagnesemia with secondary hypocalcemiaOpen Targets
0.73Strong
genetic disorderOpen Targets
0.42Moderate
nephrolithiasisOpen Targets
0.40Weak
cervical carcinomaOpen Targets
0.37Weak
bladder calculusOpen Targets
0.37Weak
HypomagnesemiaOpen Targets
0.29Weak
Antepartum hemorrhageOpen Targets
0.27Weak
neurodegenerative diseaseOpen Targets
0.27Weak
vascular dementiaOpen Targets
0.27Weak
alcohol drinkingOpen Targets
0.27Weak
Abnormality of the eyeOpen Targets
0.26Weak
Rod-cone dystrophyOpen Targets
0.26Weak
Alzheimer diseaseOpen Targets
0.25Weak
Abruptio PlacentaeOpen Targets
0.19Weak
metabolic diseaseOpen Targets
0.19Weak
examination for neoplasmOpen Targets
0.11Weak
neoplasmOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
cancerOpen Targets
0.06Suggestive
Hypomagnesemia 1UniProt
Pathogenic Variants67
NM_017662.5(TRPM6):c.3694del (p.Gln1232fs)Pathogenic
Intestinal hypomagnesemia 1|not provided
★★☆☆2025→ Residue 1232
NM_017662.5(TRPM6):c.1018C>T (p.Arg340Ter)Pathogenic
Intestinal hypomagnesemia 1|not provided
★★☆☆2025→ Residue 340
NM_017662.5(TRPM6):c.1308+7T>GPathogenic
Intestinal hypomagnesemia 1
★★☆☆2024
NM_017662.5(TRPM6):c.4287C>A (p.Cys1429Ter)Pathogenic
Intestinal hypomagnesemia 1|not provided
★★☆☆2024→ Residue 1429
NM_017662.5(TRPM6):c.166C>T (p.Arg56Ter)Pathogenic
Intestinal hypomagnesemia 1|not provided
★★☆☆2023→ Residue 56
NM_017662.5(TRPM6):c.5314C>T (p.Arg1772Ter)Pathogenic
Intestinal hypomagnesemia 1|not provided
★★☆☆2023→ Residue 1772
NM_017662.5(TRPM6):c.841+1G>APathogenic
Intestinal hypomagnesemia 1
★★☆☆2022
NM_017662.5(TRPM6):c.1966dup (p.His656fs)Pathogenic
Intestinal hypomagnesemia 1
★☆☆☆2026→ Residue 656
NM_017662.5(TRPM6):c.4193_4194insTCAG (p.Ser1399fs)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 7
★☆☆☆2026→ Residue 1399
NM_017662.5(TRPM6):c.1722C>A (p.Tyr574Ter)Pathogenic
not provided
★☆☆☆2025→ Residue 574
NM_017662.5(TRPM6):c.2232G>A (p.Trp744Ter)Pathogenic
not provided
★☆☆☆2025→ Residue 744
NM_017662.5(TRPM6):c.2573dup (p.Tyr858Ter)Pathogenic
not provided
★☆☆☆2025→ Residue 858
NM_017662.5(TRPM6):c.5742C>A (p.Tyr1914Ter)Pathogenic
Intestinal hypomagnesemia 1
★☆☆☆2025→ Residue 1914
NM_017662.5(TRPM6):c.1638+1G>ALikely pathogenic
not provided
★☆☆☆2025
NM_017662.5(TRPM6):c.5571-1G>ALikely pathogenic
not provided
★☆☆☆2024
NM_017662.5(TRPM6):c.3634C>T (p.Gln1212Ter)Likely pathogenic
Intestinal hypomagnesemia 1
★☆☆☆2024→ Residue 1212
NM_017662.5(TRPM6):c.3537-1G>ALikely pathogenic
Intestinal hypomagnesemia 1
★☆☆☆2024
NM_017662.5(TRPM6):c.1282_1283del (p.Ile428fs)Pathogenic
not provided
★☆☆☆2024→ Residue 428
NM_017662.5(TRPM6):c.1135-2A>GLikely pathogenic
Intestinal hypomagnesemia 1
★☆☆☆2024
NM_017662.5(TRPM6):c.4673-55_4734delLikely pathogenic
not provided
★☆☆☆2024
View on ClinVar ↗
Related Genes
CLDN19Protein interaction100%FXYD2Protein interaction83%CLDN16Protein interaction83%SLC41A1Protein interaction80%SLC41A3Protein interaction79%TRPV6Protein interaction79%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
31%
Lung
7%
Heart
3%
Liver
3%
Ovary
2%
Gene Interaction Network
Click a node to explore
TRPM6CLDN19FXYD2CLDN16SLC41A1SLC41A3TRPV6
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9BX84
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.49Moderately Constrained
pLIⓘ
0.02Tolerant
Observed/Expected LoF0.42 [0.35–0.49]
RankingsWhere TRPM6 stands among ~20K protein-coding genes
  • #6,687of 20,598
    Most Researched71
  • #1,088of 5,498
    Most Pathogenic Variants67 · top quartile
  • #2,932of 17,882
    Most Constrained (LOEUF)0.49 · top quartile
Genes detectedTRPM6
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Magnesium in man: implications for health and disease.
PMID: 25540137
Physiol Rev · 2015
1.00
2
Magnesium biology.
PMID: 38871680
Nephrol Dial Transplant · 2024
0.90
3
Magnesium Disorders: Core Curriculum 2024.
PMID: 38372687
Am J Kidney Dis · 2024
0.80
4
TRPM channels in health and disease.
PMID: 37853091
Nat Rev Nephrol · 2024
0.70
5
TRPM6.
PMID: 24756719
Handb Exp Pharmacol · 2014
0.60