TRPM1

Chr 15AR

transient receptor potential cation channel subfamily M member 1

Also known as: CSNB1C, LTRPC1, MLSN1

NCBI Gene: 4308 ENSG00000134160 UniProt: Q7Z4N2 OMIM: 603576

This gene encodes TRPM1, a constitutively open calcium-permeable cation channel that plays an essential role in the depolarizing photoresponse of retinal ON bipolar cells by mediating calcium and other divalent cation influx. Mutations cause autosomal recessive complete congenital stationary night blindness-1C, a condition present from birth affecting night vision. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with its recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the transient receptor potential melastatin subfamily of transient receptor potential ion channels. The encoded protein is a calcium permeable cation channel that is expressed in melanocytes and may play a role in melanin synthesis. Specific mutations in this gene are the cause autosomal recessive complete congenital stationary night blindness-1C. The expression of this protein is inversely correlated with melanoma aggressiveness and as such it is used as a prognostic marker for melanoma metastasis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.071 OMIM phenotype

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

123 unique Pathogenic / Likely Pathogenic· 650 VUS of 1445 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — TRPM1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.13Z-score

OE missense 1.01 (0.96–1.07)

914 obs / 903.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.88 (0.72–1.07)

0≤0.351.4

Missense OE?1.01 (0.96–1.07)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveTRPM1-related night blindness, congenital stationaryLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6357th %ile

GOF

0.75top 25%

LOF

0.3941th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

1445 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic68

Likely Pathogenic55

VUS650

Likely Benign491

Benign105

Conflicting72

Pathogenic

Likely Pathogenic

650

VUS

491

Likely Benign

105

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	60	0	8	0	68
Likely Pathogenic	34	18	3	0	55
VUS	14	584	43	9	650
Likely Benign	9	31	179	272	491
Benign	1	17	74	13	105
Conflicting	—				72
Total	118	650	307	294	1,441

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

181 pathogenic / likely-pathogenic (of 246) ClinVar copy-number / structural variants overlap TRPM1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →