TRPM7

Chr 15AD

transient receptor potential cation channel subfamily M member 7

Also known as: ALSPDC, CHAK, CHAK1, LTRPC7, LTrpC-7, TRP-PLIK

NCBI Gene: 54822 ENSG00000092439 UniProt: Q96QT4 OMIM: 605692

This gene belongs to the melastatin subfamily of transient receptor potential family of ion channels. The protein encoded by this gene is both an ion channel and a serine/threonine protein kinase. The kinase activity is essential for the ion channel function, which serves to increase intracellular calcium levels and to help regulate magnesium ion homeostasis. The encoded protein is involved in cytoskeletal organization, cell adhesion, cell migration and organogenesis. Defects in this gene are a cause of amyotrophic lateral sclerosis-parkinsonism/dementia complex of Guam. The gene may also be associated with defects of cardiac function. [provided by RefSeq, Aug 2017]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to}MIM #105500

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · macrothrombocytopenia, isolated · AD · ClinGen 2024

Active trials

119

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.56

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.56LOEUF

pLI 0.000

Z-score 5.29

OE 0.43 (0.34–0.56)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.23Z-score

OE missense 0.80 (0.75–0.84)

756 obs / 949.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.43 (0.34–0.56)

0≤0.351.4

Missense OE?0.80 (0.75–0.84)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 44 / 101.5Missense obs/exp: 756 / 949.6Syn Z: -0.47

Background carrier burden — how many people carry a rare variant somewhere in TRPM7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 36

2,082 rare PASS variants

Rare truncating (LoF)

1 in 840

281 rare PASS variants

Rare synonymous (reference)

1 in 94

760 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRPM7. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 50	1 in 930
South Asian	~43k	1 in 42	1 in 560
Remaining (unassigned)	~30k	1 in 36	1 in 500
European (Finnish)	~27k	1 in 140	1 in 1,100
Admixed American	~22k	1 in 32	1 in 870
African / African American	~21k	1 in 36	1 in 700
East Asian	~20k	1 in 37	1 in 940
Ashkenazi Jewish	~13k	1 in 230	1 in 830
Middle Eastern	~2,884	1 in 39	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 30 of 39 coding exons well covered in gnomAD exomes; exons 8, 10, 11, 20, 23 and 4 more marginal. Genomes: all 39.? see exons ↓