MCOLN3

mucolipin TRP cation channel 3, the group of Transient receptor potential cation channels

Basic information

Region (hg38): 1:85018081-85048500

Links

ENSG00000055732 ∙ NCBI:55283 ∙ OMIM:607400 ∙ HGNC:13358 ∙ Uniprot:Q8TDD5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MCOLN3 gene.

• Inborn genetic diseases (20 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MCOLN3 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				1		1
missense			20			20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	20	1	0

Variants in MCOLN3

This is a list of pathogenic ClinVar variants found in the MCOLN3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-85019152-C-G		not specified	Uncertain significance (May 24, 2023)
1-85021137-C-A		not specified	Uncertain significance (Feb 10, 2022)
1-85021203-G-A		not specified	Uncertain significance (Feb 26, 2024)
1-85022166-C-T			Likely benign (Jul 01, 2022)
1-85025973-A-G		not specified	Uncertain significance (Oct 06, 2021)
1-85025987-G-T		not specified	Uncertain significance (Dec 21, 2023)
1-85026072-A-T		not specified	Uncertain significance (Apr 18, 2023)
1-85026195-T-C		not specified	Likely benign (Jan 03, 2024)
1-85026263-A-C		not specified	Uncertain significance (Jan 27, 2022)
1-85029150-T-C		not specified	Uncertain significance (May 01, 2022)
1-85029153-T-C		not specified	Uncertain significance (Dec 09, 2023)
1-85032757-G-T		not specified	Uncertain significance (May 02, 2023)
1-85032945-C-T		not specified	Uncertain significance (Jan 20, 2023)
1-85034113-G-C		not specified	Uncertain significance (Dec 16, 2022)
1-85034148-T-G		not specified	Uncertain significance (Oct 12, 2021)
1-85034227-C-T		not specified	Uncertain significance (Jan 24, 2024)
1-85034239-A-G		not specified	Uncertain significance (Oct 03, 2022)
1-85041035-T-C		not specified	Uncertain significance (Jun 05, 2023)
1-85041056-T-C		not specified	Uncertain significance (Jun 27, 2022)
1-85041087-T-C		not specified	Uncertain significance (Jul 19, 2023)
1-85041107-T-C		not specified	Uncertain significance (Nov 09, 2023)
1-85045147-T-C		not specified	Uncertain significance (Mar 13, 2023)
1-85045162-T-C		not specified	Uncertain significance (Dec 28, 2023)
1-85045194-C-T		not specified	Uncertain significance (Oct 26, 2022)
1-85045215-G-C		not specified	Uncertain significance (Dec 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MCOLN3	protein_coding	protein_coding	ENST00000370589	12	30418

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.32e-11	0.870	125604	2	142	125748	0.000573

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.623	260	290	0.897	0.0000142	3704
Missense in Polyphen		73	84.508	0.86383		1087
Synonymous	1.43	82	100	0.819	0.00000498	981
Loss of Function	1.82	21	32.1	0.654	0.00000187	352

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000995	0.000993
Ashkenazi Jewish	0.000109	0.0000992
East Asian	0.000328	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000229	0.000229
Middle Eastern	0.000328	0.000326
South Asian	0.00295	0.00285
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Nonselective ligand-gated cation channel probably playing a role in the regulation of membrane trafficking events. Acts as Ca(2+)-permeable cation channel with inwardly rectifying activity (PubMed:18369318, PubMed:19497048, PubMed:19522758, PubMed:19885840, PubMed:29106414). Mediates release of Ca(2+) from endosomes to the cytoplasm, contributes to endosomal acidification and is involved in the regulation of membrane trafficking and fusion in the endosomal pathway (PubMed:21245134). Does not seem to act as mechanosensory transduction channel in inner ear sensory hair cells. Proposed to play a critical role at the cochlear stereocilia ankle-link region during hair-bundle growth (By similarity). Involved in the regulation of autophagy (PubMed:19522758). Through association with GABARAPL2 may be involved in autophagosome formation possibly providing Ca(2+) for the fusion process (By similarity). Through a possible and probably tissue-specific heteromerization with MCOLN1 may be at least in part involved in many lysosome-dependent cellular events (PubMed:19885840). Possible heteromeric ion channel assemblies with TRPV5 show pharmacological similarity with TRPML3 (PubMed:23469151). {ECO:0000250|UniProtKB:Q8R4F0, ECO:0000269|PubMed:18369318, ECO:0000269|PubMed:19497048, ECO:0000269|PubMed:19522758, ECO:0000269|PubMed:19885840, ECO:0000269|PubMed:20378547, ECO:0000269|PubMed:21245134, ECO:0000269|PubMed:23469151, ECO:0000269|PubMed:29106414, ECO:0000305}.
• Pathway: Stimuli-sensing channels;Ion channel transport;Transport of small molecules;TRP channels (Consensus)

Recessive Scores

• pRec: 0.133

Intolerance Scores

• loftool: 0.582
• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.12

Haploinsufficiency Scores

• pHI: 0.102
• hipred: N
• hipred_score: 0.476
• ghis: 0.555

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.210

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mcoln3
• Phenotype: growth/size/body region 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); reproductive system phenotype; pigmentation phenotype; limbs/digits/tail phenotype; 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); hearing/vestibular/ear phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: locomotory behavior;inner ear auditory receptor cell differentiation;release of sequestered calcium ion into cytosol;calcium ion transmembrane transport
• Cellular component: autophagosome membrane;lysosomal membrane;plasma membrane;integral component of membrane;early endosome membrane;late endosome membrane
• Molecular function: calcium channel activity;lipid binding;NAADP-sensitive calcium-release channel activity