GeneBe

TRPM1

protein-coding

transient receptor potential cation channel subfamily M member 1, the group of MicroRNA protein coding host genes|Transient receptor potential cation channels

Gene summary

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]

Previous symbols:
  • MLSN1

MANE transcript

NM_001252024.2

Inheritance

AR

ClinVar variants

P:149U:651B:394

Top phenotype

Night blindness, congenital stationary, type 1C

gnomAD constraint

pLI —, LoF o/e 0.88

Max pathogenic AF

—

Genomic locus

chr15:31,001,065-31,161,160

External References & Databases

Ensembl (ENSG00000134160)NCBI Gene (4308)OMIM (603576)HGNC:7146GenCCUniProt (Q7Z4N2)AlphaFoldClinVar (TRPM1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~160.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital stationary night blindness 1CSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013183

Submitter: PanelApp Australia

congenital stationary night blindness 1CDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013183

Submitter: G2P

TRPM1-related retinopathyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0800402

Submitter: ClinGen

*TRPM1* was first reported in relation to autosomal recessive cases of congenital stationary night blindness type 1C by three groups in 2009 (PMIDs: 19878917, 19896109, 19896113). The hallmark CSNB phenotype is night blindness from birth or early childhood with a severely reduced or completely absent scotopic b-wave in an ERG, but normal or mildly affected a-wave. Patients also commonly present with myopia, nystagmus and/or strabismus. Because of the broad spectrum of potential phenotypes, these cases with causal variants in *TRPM1* have been curated under the inclusive disease name *TRPM1*-related retinopathy (MONDO:0800402). Twelve variants (four nonsense, three missense, two frameshift, and three intronic) that have been reported in eight probands in five publications (PMIDs: 35633130, 19896113, 20300565, 19896109, 19878917) are included in this curation. The mechanism of pathogenicity appears to be biallelic loss-of-function. This gene-disease association is also supported by experimental evidence that *TRPM1* exhibits its highest expression levels in retina tissue (PMID: 19878917). Additionally, expression of TRPM1 in the retina of horses with a CSNB phenotype is 0.05% of the level found in horses with normal vision (PMID: 18660533). Immunolocalization shows that TRPM1 is localized to ON bipolar cell dendrites in the outer plexiform layer (OPL) of the retina (PMID: 19896109). The ERG b-wave is absent (a defining phenotype of CSNB) in a *Trpm1 (-/-)* knockout mouse (PMID: 20300565). These ERG results have been replicated in another *Trpm1* null mutant mouse experiment (PMID: 19861548). Furthermore, this group has also found that TRPM1 immuno-staining is absent in the OPL layer of retinal cells in *Trpm1(−/−)* mice. They go on to show that OKR response is reduced in knockout mice. Finally, these authors show that cell response is absent (in rod cells) or highly altered (in cone cells) in *Trpm1 (-/-)* mice (PMID: 19861548). In summary, *TRPM1* is definitively associated with autosomal recessive inheritance of *TRPM1*-related retinopathy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time without the emergence of contradictory evidence, leading to a Definitive classification according to the ClinGen template. This classification was approved by the ClinGen Retina GCEP on October 6, 2022 (SOP Version 9).

congenital stationary night blindness 1CSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013183

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Night blindness, congenital stationary, type 1CAR

Manifestation: Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Comments: Dermatologic findings (eg, dry skin; a condition resembling epidermolysis bullosa simplex) have been described, but it is not clear if these are part of the core phenotype

Refs: 19896113; 19878917; 19896109; 20300565Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TRPM1 variants in ClinVar

15 Conditions Cataloged
not providedTotal: 1244
TRPM1-related disorderTotal: 235
Inborn genetic diseasesTotal: 212
not specifiedTotal: 197
Congenital stationary night blindness 1CTotal: 154
Retinal dystrophyTotal: 19
Congenital stationary night blindnessTotal: 11
Retinal disorderTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001252024.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
7
clinvar
316
clinvar
3
clinvar
 328
missense
1
clinvar
34
clinvar
634
clinvar
64
clinvar
2
clinvar
 735
nonsense
18
clinvar
17
clinvar
2
clinvar
3
clinvar
 40
start loss
0
frameshift
26
clinvar
16
clinvar
8
clinvar
6
clinvar
 56
splice donor/acceptor (+/-2bp)
5
clinvar
30
clinvar
 35
Total509965138951194

Highest pathogenic variant AF is 0.00030605064

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001252024.2RefSeqNP_001238953.127MANE Select
ENST00000256552.11EnsemblENSP00000256552.727MANE Select
NM_001252020.2RefSeqNP_001238949.127Standard
NM_001252030.2RefSeqNP_001238959.12Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Stimuli-sensing channels
  • Ion channel transport
  • Transport of small molecules
  • TRP channels

Biological Process

  • G protein-coupled glutamate receptor signaling pathway
  • visual perception
  • retinal rod cell development
  • protein tetramerization
  • calcium ion transport into cytosol

Molecular Function

  • calcium channel activity

Cellular Component

  • plasma membrane
  • integral component of plasma membrane
  • new growing cell tip

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000542188
Coding exons
27
Length
160213
Individuals with no LoFs
109924
Homozygous LoFs
681
Heterozygous LoFs
14678
Defined
125283
p
0.0633
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.1319149031.010.000056110813
Missense (PolyPhen)347355.740.975434200
Synonymous-0.9813803561.070.00002393120
Loss of Function1.037080.00.8750.00000457942

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0820.080notable
Latino/Admixed American0.0350.035notable
Ashkenazi Jewish0.0700.069notable
East Asian0.0110.011notable
Finnish0.0690.069notable
European (Non-Finnish)0.0590.059notable
South Asian0.130.13notable
Other0.0660.066notable

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Cation channel essential for the depolarizing photoresponse of retinal ON bipolar cells. It is part of the GRM6 signaling cascade. May play a role in metastasis suppression (By similarity). May act as a spontaneously active, calcium-permeable plasma membrane channel. {ECO:0000250, ECO:0000269|PubMed:11535825, ECO:0000269|PubMed:19878917, ECO:0000269|PubMed:19896109}.;
Disease
DISEASE: Night blindness, congenital stationary, 1C (CSNB1C) [MIM:613216]: A non-progressive retinal disorder characterized by impaired night vision, often associated with nystagmus and myopia. {ECO:0000269|PubMed:19878917, ECO:0000269|PubMed:19896109, ECO:0000269|PubMed:19896113}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.140

Intolerance Scores

LoFtool
0.884
RVIS EVS
1.75
RVIS percentile EVS
96.69

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.156

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.