MCOLN3

protein-coding

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

Gene summary

This gene encodes one of members of the mucolipin cation channel proteins. Mutation studies of the highly similar protein in mice have shown that the protein is found in cochlea hair cells, and mutant mice show early-onset hearing loss and balance problems. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

MANE transcript

NM_018298.11

Inheritance

—

ClinVar variants

U:68B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr1:85,018,082-85,048,500

External References & Databases

Ensembl (ENSG00000055732)

Transcript & Mutation Effects

hg38 • Region Span ~30.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MCOLN3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 64

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018298.11. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	1 clinvar		3
missense			65 clinvar	1 clinvar		66
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	68	2	0	70

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 62 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018298.11	RefSeq	NP_060768.8	12	MANE Select
ENST00000370589.7	Ensembl	ENSP00000359621.1	12	MANE Select
NM_001253693.2	RefSeq	NP_001240622.1	11	Standard
ENST00000341115.8	Ensembl	ENSP00000342698.3	11	Standard

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

locomotory behavior
inner ear auditory receptor cell differentiation
release of sequestered calcium ion into cytosol
calcium ion transmembrane transport

Molecular Function

calcium channel activity
lipid binding
NAADP-sensitive calcium-release channel activity

Cellular Component

autophagosome membrane
lysosomal membrane
plasma membrane
integral component of membrane
early endosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370589
Coding exons: 12
Length: 30418
Individuals with no LoFs: 125604
Homozygous LoFs: 2
Heterozygous LoFs: 142
Defined: 125748
p: 0.000573

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.623	260	290	0.897	0.0000142	3704
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00062	0.00062	rare
Latino/Admixed American	0.00038	0.00038	rare
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.0030	0.0028	notable
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.133

Intolerance Scores

LoFtool: 0.582
RVIS EVS: -0.69
RVIS percentile EVS: 15.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.210

Gene Damage Prediction

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