TRPM1

Chr 15AR

transient receptor potential cation channel subfamily M member 1

NCBI Gene: 4308 ENSG00000134160 UniProt: Q7Z4N2

Constitutively open nonselective divalent cation-conducting channels which mediate the influx of Ca(2+), Mg(2+), Mn(2+), Ba(2+), and Ni(2+) into the cytoplasm, leading to membrane depolarization (PubMed:11535825, PubMed:19436059, PubMed:21278253). Impermeable to zinc ions (PubMed:21278253). In addition, forms heteromultimeric ion channels with TRPM3 which are permeable for calcium and zinc ions (PubMed:21278253). Plays an essential role for the depolarizing photoresponse of retinal ON bipolar cells (PubMed:19878917, PubMed:19896109). In the dark, tonic release of glutamate activates the G-protein coupled receptor for glutamate, GRM6, its activation induces the release of G(o) protein and the beta-gamma G protein dimer. Both subunits can interact and inactivate the TRPM1 channel. A light onset, induces decrease in glutamate release and deactivation of GRM6 leading to channel opening and membrane depolarization (By similarity). May play a role in metastasis suppression (PubMed:9537257)

Primary Disease Associations & Inheritance

Night blindness, congenital stationary (complete), 1C, autosomal recessiveMIM #613216

596

ClinVar variants

Pathogenic / LP

0.00

pLI score

Active trials

Clinical Summary— TRPM1

🧬

Gene-Disease Validity (ClinGen)

TRPM1-related retinopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

88 Pathogenic / Likely Pathogenic· 261 VUS of 596 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

1.07LOEUF

pLI 0.000

Z-score 1.03

OE 0.88 (0.72–1.07)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

-0.13Z-score

OE missense 1.01 (0.96–1.07)

914 obs / 903.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.88 (0.72–1.07)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.96–1.07)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07

0≤1.21.6

LoF obs/exp: 70 / 80.0Missense obs/exp: 914 / 903.0Syn Z: -0.98