MCOLN2

Chr 1

mucolipin TRP cation channel 2

Also known as: TRP-ML2, TRPML2

NCBI Gene: 255231 ENSG00000153898 UniProt: Q8IZK6

The MCOLN2 protein functions as a nonselective cation channel that regulates membrane trafficking events and plays roles in immune processes including chemokine secretion and macrophage migration. Unlike MCOLN1 mutations which cause mucolipidosis IV, no specific human diseases have been definitively linked to MCOLN2 mutations despite the gene being expressed and functionally characterized. The gene shows minimal constraint against loss-of-function variants (very low pLI), suggesting haploinsufficiency may be well-tolerated.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.19

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.19LOEUF

pLI 0.000

Z-score 0.77

OE 0.84 (0.61–1.19)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.53Z-score

OE missense 0.91 (0.83–1.01)

278 obs / 303.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.84 (0.61–1.19)

0≤0.351.4

Missense OE?0.91 (0.83–1.01)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 24 / 28.4Missense obs/exp: 278 / 303.9Syn Z: -0.42

Background carrier burden — how many people carry a rare variant somewhere in MCOLN2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 90

675 rare PASS variants

Rare truncating (LoF)

1 in 840

133 rare PASS variants

Rare synonymous (reference)

1 in 180

254 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MCOLN2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 1,800
South Asian	~43k	1 in 58	1 in 470
Remaining (unassigned)	~30k	1 in 91	1 in 410
European (Finnish)	~27k	1 in 550	1 in 3,800
Admixed American	~22k	1 in 73	1 in 830
African / African American	~21k	1 in 58	1 in 540
East Asian	~20k	1 in 73	1 in 2,000
Ashkenazi Jewish	~13k	1 in 430	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 60	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 14 coding exons well covered in gnomAD exomes; exons 7, 14 marginal. Genomes: all 14.? see exons ↓