TRPM3

transient receptor potential cation channel subfamily M member 3, the group of MicroRNA protein coding host genes|Transient receptor potential cation channels

Basic information

Region (hg38): 9:70529059-71446904

Links

ENSG00000083067 ∙ NCBI:80036 ∙ OMIM:608961 ∙ HGNC:17992 ∙ Uniprot:Q9HCF6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• schizophrenia (No Known Disease Relationship), mode of inheritance: Unknown
• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
• schizophrenia (Limited), mode of inheritance: AD
• intellectual disability (Limited), mode of inheritance: AD
• cataract-glaucoma syndrome (Limited), mode of inheritance: AD
• neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures (Strong), mode of inheritance: AD
• cataract 50 with or without glaucoma (Strong), mode of inheritance: AD
• neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cataract 50 with or without glaucoma	AD	Ophthalmologic	The condition can include risk of glaucoma, and awareness may allow surveillance and early management	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	25090642,; 31278393; 32343227; 32439617; 32427099; 33484482; 34438093; 35146895

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRPM3 gene.

• not provided (84 variants)
• Inborn genetic diseases (34 variants)
• TRPM3-related condition (4 variants)
• Neurodevelopmental disorder (3 variants)
• Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures (3 variants)
• not specified (2 variants)
• Developmental disorder (1 variants)
• TRPM3-associated epilepsy syndrome (1 variants)
• Birk-Barel syndrome (1 variants)
• See cases (1 variants)
• TRPM3 related neruodevelopmental disorder (1 variants)
• Mulibrey nanism syndrome (1 variants)
• Intellectual disability;Epileptic encephalopathy (1 variants)
• TRPM3-related Intellectual Disability and Epilepsy (1 variants)
• Intellectual disability (1 variants)
• Seizure;Global developmental delay (1 variants)
• Familial progressive retinal dystrophy-iris coloboma-congenital cataract syndrome (1 variants)
• TRPM3 related disorder (1 variants)
• Seizure (1 variants)
• Autosomal dominant non-syndromic intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRPM3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	6	8
missense		6	88	6	3	103
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			2			2
splice region			1	1	1	3
non coding	1		11	1	1	14
Total	1	6	103	9	10

Variants in TRPM3

This is a list of pathogenic ClinVar variants found in the TRPM3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-70535990-G-A			Uncertain significance (Nov 14, 2022)
9-70536026-C-T		Intellectual disability;Epileptic encephalopathy	Uncertain significance (Nov 30, 2021)
9-70536043-G-C		TRPM3-related disorder	Likely benign (Jun 11, 2019)
9-70536068-C-T			Benign (Sep 25, 2020)
9-70536086-C-T		Inborn genetic diseases	Uncertain significance (Dec 28, 2022)
9-70536087-G-A		Inborn genetic diseases	Uncertain significance (May 09, 2023)
9-70536108-T-G			Uncertain significance (May 15, 2020)
9-70536143-G-A		TRPM3-related disorder	Benign/Likely benign (May 01, 2022)
9-70536143-G-T		Inborn genetic diseases	Uncertain significance (Dec 07, 2023)
9-70536170-T-C		Inborn genetic diseases	Uncertain significance (Feb 22, 2023)
9-70536175-G-A		TRPM3-related disorder	Likely benign (Mar 12, 2019)
9-70536191-A-C		Inborn genetic diseases	Uncertain significance (Nov 06, 2023)
9-70536194-G-A		TRPM3-related disorder	Benign (Apr 04, 2019)
9-70536200-T-C			Likely pathogenic (Oct 08, 2021)
9-70536224-T-A		TRPM3-related disorder	Benign (Feb 19, 2019)
9-70536251-A-G		Inborn genetic diseases	Uncertain significance (Feb 14, 2023)
9-70536345-C-A		Inborn genetic diseases	Uncertain significance (Mar 01, 2024)
9-70536415-C-A		Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures	Uncertain significance (Dec 19, 2023)
9-70536426-T-C		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
9-70536428-C-T		Developmental disorder	Likely benign (Jan 06, 2022)
9-70536471-C-T		TRPM3-related disorder	Likely benign (Apr 01, 2024)
9-70536476-T-C			Uncertain significance (Jan 02, 2020)
9-70536546-G-C		Inborn genetic diseases	Uncertain significance (Nov 03, 2023)
9-70536569-C-T		Inborn genetic diseases	Uncertain significance (Nov 28, 2023)
9-70536620-C-G		Neurodevelopmental disorder	Uncertain significance (Jun 24, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRPM3	protein_coding	protein_coding	ENST00000377110	25	917842

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.69e-7	1.00	125670	0	78	125748	0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.18	716	998	0.717	0.0000576	11294
Missense in Polyphen		289	471.78	0.61257		5303
Synonymous	0.133	374	377	0.991	0.0000230	3243
Loss of Function	5.64	27	82.2	0.329	0.00000471	917

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000695	0.000695
Ashkenazi Jewish	0.000710	0.000695
East Asian	0.00	0.00
Finnish	0.000278	0.000277
European (Non-Finnish)	0.000328	0.000325
Middle Eastern	0.00	0.00
South Asian	0.000370	0.000359
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Calcium channel mediating constitutive calcium ion entry. Its activity is increased by reduction in extracellular osmolarity, by store depletion and muscarinic receptor activation. {ECO:0000269|PubMed:12672799, ECO:0000269|PubMed:12672827}.
• Pathway: Stimuli-sensing channels;Ion channel transport;Transport of small molecules;TRP channels (Consensus)

Recessive Scores

• pRec: 0.114

Intolerance Scores

• loftool: 0.767
• rvis_EVS: -1.09
• rvis_percentile_EVS: 6.98

Haploinsufficiency Scores

• pHI: 0.476
• hipred: Y
• hipred_score: 0.747
• ghis: 0.575

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0628

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	High	Medium	High

Mouse Genome Informatics

• Gene name: Trpm3
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: cation transport;detection of temperature stimulus;sensory perception of temperature stimulus;protein tetramerization;calcium ion transmembrane transport
• Cellular component: plasma membrane;integral component of membrane
• Molecular function: calcium activated cation channel activity;cation channel activity;calcium channel activity