MCOLN2
protein-codingmucolipin TRP cation channel 2, the group of Transient receptor potential cation channels
Gene summary
Mucolipins constitute a family of cation channel proteins with homology to the transient receptor potential superfamily. In mammals, the mucolipin family includes 3 members, MCOLN1 (MIM 605248), MCOLN2, and MCOLN3 (MIM 607400), that exhibit a common 6-membrane-spanning topology. Homologs of mammalian mucolipins exist in Drosophila and C. elegans. Mutations in the human MCOLN1 gene cause mucolipodosis IV (MIM 262650) (Karacsonyi et al., 2007 [PubMed 17662026]).[supplied by OMIM, Sep 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~71.5 kbGenCC 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 MCOLN2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_153259.4. 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 | 1 | 1 | 2 | |||
| missense | 76 | 6 | 3 | 85 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 77 | 6 | 4 | 87 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_694991.2 | 14 | MANE Select | |
| Ensembl | ENSP00000359640.3 | 14 | MANE Select | |
| RefSeq | NP_001317576.1 | 13 | Standard | |
| Ensembl | ENSP00000284027.5 | 13 | 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
- adaptive immune response
- chemokine (C-C motif) ligand 2 secretion
- innate immune response
- release of sequestered calcium ion into cytosol
- protein complex oligomerization
Molecular Function
- calcium channel activity
- NAADP-sensitive calcium-release channel activity
Cellular Component
- lysosomal membrane
- plasma membrane
- integral component of membrane
- late endosome membrane
- recycling endosome membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000370608
- Coding exons
- 14
- Length
- 71529
- Individuals with no LoFs
- 125561
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 184
- Defined
- 125746
- p
- 0.000736
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.527 | 278 | 304 | 0.915 | 0.0000155 | 3763 |
| Missense (PolyPhen) | 87 | 110.59 | 0.78666 | 1384 | ||
| Synonymous | -0.419 | 113 | 107 | 1.05 | 0.00000555 | 1005 |
| Loss of Function | 0.768 | 24 | 28.4 | 0.845 | 0.00000128 | 377 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00055 | 0.00055 | rare |
| Latino/Admixed American | 0.00029 | 0.00029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.0035 | 0.0034 | notable |
| Finnish | 0.0020 | 0.0020 | notable |
| European (Non-Finnish) | 0.00033 | 0.00033 | rare |
| South Asian | 0.00054 | 0.00052 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Nonselective 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:19940139, PubMed:19885840). May activate ARF6 and be involved in the trafficking of GPI-anchored cargo proteins to the cell surface via the ARF6-regulated recycling pathway (PubMed:17662026). May play a role in immune processes. In adaptive immunity, TRPML2 and TRPML1 may play redundant roles in the function of the specialized lysosomes of B cells (By similarity). In the innate immune response, may play a role in the regulation of chemokine secretion and macrophage migration (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). {ECO:0000250|UniProtKB:Q8K595, ECO:0000269|PubMed:17662026, ECO:0000269|PubMed:19885840, ECO:0000269|PubMed:19940139, ECO:0000305}.;
Recessive Scores
- pRec
- 0.0834
Intolerance Scores
- RVIS EVS
- 0.71
- RVIS percentile EVS
- 85.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0502
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |