MCOLN2

mucolipin TRP cation channel 2, the group of Transient receptor potential cation channels

Basic information

Region (hg38): 1:84925582-84997113

Links

ENSG00000153898 ∙ NCBI:255231 ∙ OMIM:607399 ∙ HGNC:13357 ∙ Uniprot:Q8IZK6 ∙ 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 MCOLN2 gene.

• Inborn genetic diseases (19 variants)
• not provided (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MCOLN2 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			19		3	22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	0	0	19	0	6

Variants in MCOLN2

This is a list of pathogenic ClinVar variants found in the MCOLN2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-84926717-T-C		not specified	Likely benign (Nov 22, 2023)
1-84929565-G-A		not specified	Uncertain significance (Apr 22, 2022)
1-84929567-C-G		not specified	Uncertain significance (Jan 29, 2024)
1-84929651-G-C		not specified	Uncertain significance (Oct 30, 2023)
1-84931381-T-C		not specified	Uncertain significance (Oct 03, 2022)
1-84931454-G-A		not specified	Uncertain significance (Nov 07, 2023)
1-84937762-T-C		not specified	Uncertain significance (Sep 13, 2023)
1-84937834-C-T		not specified	Uncertain significance (May 05, 2023)
1-84937887-A-T			Benign (Feb 20, 2018)
1-84938028-C-G		not specified	Uncertain significance (Apr 20, 2023)
1-84938036-G-A		not specified	Uncertain significance (Dec 20, 2022)
1-84939543-C-T			Benign (Jun 18, 2018)
1-84939555-T-G			Benign (Aug 03, 2017)
1-84939570-T-C			Benign (Jun 18, 2018)
1-84939674-T-G		not specified	Uncertain significance (Oct 27, 2023)
1-84940883-C-T		not specified	Uncertain significance (Jun 30, 2023)
1-84947114-C-A		not specified	Uncertain significance (Sep 26, 2022)
1-84952244-G-A		not specified	Uncertain significance (Mar 02, 2023)
1-84952278-G-A		not specified	Uncertain significance (May 23, 2023)
1-84952304-C-A		not specified	Uncertain significance (Dec 11, 2023)
1-84952313-T-A		not specified	Uncertain significance (Jul 14, 2023)
1-84952488-G-A		not specified	Uncertain significance (Jun 21, 2023)
1-84952504-G-A		not specified	Uncertain significance (Jan 19, 2022)
1-84956443-C-T		not specified	Uncertain significance (Jan 02, 2024)
1-84956481-G-T		not specified	Uncertain significance (Apr 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MCOLN2	protein_coding	protein_coding	ENST00000370608	14	71529

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.25e-14	0.0835	125561	1	184	125746	0.000736

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.527	278	304	0.915	0.0000155	3763
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000849	0.000848
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.00349	0.00343
Finnish	0.00203	0.00203
European (Non-Finnish)	0.000327	0.000325
Middle Eastern	0.00349	0.00343
South Asian	0.000536	0.000523
Other	0.000817	0.000815

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Stimuli-sensing channels;Ion channel transport;Transport of small molecules;TRP channels (Consensus)

Recessive Scores

• pRec: 0.0834

Intolerance Scores

• rvis_EVS: 0.71
• rvis_percentile_EVS: 85.73

Haploinsufficiency Scores

• pHI: 0.0851
• hipred: N
• hipred_score: 0.197
• ghis: 0.479

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0502

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mcoln2
• Phenotype: immune system phenotype; hematopoietic system phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• 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;calcium ion transmembrane transport;positive regulation of monocyte chemotactic protein-1 production;positive regulation of macrophage inflammatory protein 1 alpha production;positive regulation of chemokine (C-C motif) ligand 5 production;macrophage migration;neutrophil migration;positive regulation of chemokine (C-X-C motif) ligand 2 production
• Cellular component: lysosomal membrane;plasma membrane;integral component of membrane;late endosome membrane;recycling endosome membrane
• Molecular function: calcium channel activity;NAADP-sensitive calcium-release channel activity