MCOLN1
mucolipin TRP cation channel 1, the group of Transient receptor potential cation channels
Basic information
Region (hg38): 19:7522624-7534009
Links
Phenotypes
GenCC
Source:
- mucolipidosis type IV (Definitive), mode of inheritance: AR
- mucolipidosis type IV (Definitive), mode of inheritance: AR
- mucolipidosis type IV (Strong), mode of inheritance: AR
- mucolipidosis type IV (Definitive), mode of inheritance: AR
- mucolipidosis type IV (Strong), mode of inheritance: AR
- mucolipidosis type IV (Supportive), mode of inheritance: AR
- mucolipidosis type IV (Definitive), mode of inheritance: AR
- Lisch epithelial corneal dystrophy (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Corneal dystrophy, Lisch epithelial; Mucolipidosis IV | AD/AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Biochemical; Neurologic; Ophthalmologic | 4365943; 166049; 7114093; 3918453; 2438637; 1789285; 9323557; 9600972; 9710036; 10973263; 11030752; 15523648; 17239335; 19006653; 20159435; 37972748 |
ClinVar
This is a list of variants' phenotypes submitted to
- Mucolipidosis_type_IV (848 variants)
- Inborn_genetic_diseases (106 variants)
- not_provided (77 variants)
- Lisch_epithelial_corneal_dystrophy (26 variants)
- MCOLN1-related_disorder (12 variants)
- not_specified (9 variants)
- Growth_delay (2 variants)
- Intellectual_disability (2 variants)
- Atrophy/Degeneration_affecting_the_brainstem (2 variants)
- Delayed_speech_and_language_development (2 variants)
- Corneal_opacity (2 variants)
- Periventricular_leukomalacia (2 variants)
- Delayed_myelination (2 variants)
- Hereditary_spastic_paraplegia_5A (1 variants)
- Hereditary_spastic_paraplegia_39 (1 variants)
- See_cases (1 variants)
- EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
- Mucolipidosis (1 variants)
- Abnormality_of_the_nervous_system (1 variants)
- Retinal_dystrophy (1 variants)
- Spastic_Paraplegia,_Recessive (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MCOLN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020533.3. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 10 | 343 | 354 | |||
| missense | 10 | 153 | 23 | 187 | ||
| nonsense | 15 | 14 | 30 | |||
| start loss | 2 | 2 | ||||
| frameshift | 30 | 19 | 52 | |||
| splice donor/acceptor (+/-2bp) | 22 | 30 | ||||
| Total | 54 | 66 | 167 | 367 | 1 |
Highest pathogenic variant AF is 0.00010472489
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MCOLN1 | protein_coding | protein_coding | ENST00000264079 | 14 | 11384 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000580 | 0.999 | 125655 | 0 | 93 | 125748 | 0.000370 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.61 | 272 | 358 | 0.760 | 0.0000264 | 3769 |
| Missense in Polyphen | 98 | 150.43 | 0.65147 | 1738 | ||
| Synonymous | -1.52 | 187 | 162 | 1.15 | 0.0000129 | 1199 |
| Loss of Function | 3.23 | 11 | 30.1 | 0.365 | 0.00000176 | 318 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000235 | 0.000235 |
| Ashkenazi Jewish | 0.00427 | 0.00428 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000318 | 0.000316 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.000196 | 0.000196 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Nonselective cation channel probably playing a role in the regulation of membrane trafficking events and of metal homeostasis. Proposed to play a major role in Ca(2+) release from late endosome and lysosome vesicles to the cytoplasm, which is important for many lysosome-dependent cellular events, including the fusion and trafficking of these organelles, exocytosis and autophagy (PubMed:11013137, PubMed:12459486, PubMed:15336987, PubMed:14749347, PubMed:29019983). Required for efficient uptake of large particles in macrophages in which Ca(2+) release from the lysosomes triggers lysosomal exocytosis. May also play a role in phagosome-lysosome fusion (By similarity). Involved in lactosylceramide trafficking indicative for a role in the regulation of late endocytic membrane fusion/fission events (PubMed:16978393). By mediating lysosomal Ca(2+) release is involved in regulation of mTORC1 signaling and in mTOR/TFEB- dependent lysosomal adaptation to environmental cues such as nutrient levels (PubMed:27787197, PubMed:25733853). Seems to act as lysosomal active oxygen species (ROS) sensor involved in ROS- induced TFEB activation and autophagy (PubMed:27357649). Functions as a Fe(2+) permeable channel in late endosomes and lysosomes (PubMed:18794901). Proposed to play a role in zinc homeostasis probably implicating its association with TMEM163 (PubMed:25130899) In adaptive immunity, TRPML2 and TRPML1 may play redundant roles in the function of the specialized lysosomes of B cells (By similarity). {ECO:0000250|UniProtKB:Q99J21, ECO:0000269|PubMed:12459486, ECO:0000269|PubMed:14749347, ECO:0000269|PubMed:15336987, ECO:0000269|PubMed:16978393, ECO:0000269|PubMed:18794901, ECO:0000269|PubMed:25130899, ECO:0000269|PubMed:25733853, ECO:0000269|PubMed:27357649, ECO:0000269|PubMed:27787197, ECO:0000269|PubMed:29019983, ECO:0000305|PubMed:11013137}.;
- Disease
- DISEASE: Mucolipidosis 4 (ML4) [MIM:252650]: An autosomal recessive lysosomal storage disorder characterized by severe psychomotor retardation and ophthalmologic abnormalities, including corneal opacity, retinal degeneration and strabismus. Storage bodies of lipids and water-soluble substances are seen by electron microscopy in almost every cell type of the patients. Most patients are unable to speak or walk independently and reach a maximal developmental level of 1-2 years. All patients have constitutive achlorhydia associated with a secondary elevation of serum gastrin levels. {ECO:0000269|PubMed:10973263, ECO:0000269|PubMed:11013137, ECO:0000269|PubMed:11030752, ECO:0000269|PubMed:11317355, ECO:0000269|PubMed:12182165, ECO:0000269|PubMed:14749347, ECO:0000269|PubMed:15178326, ECO:0000269|PubMed:15523648, ECO:0000269|PubMed:16978393, ECO:0000269|PubMed:18794901, ECO:0000269|PubMed:21256127, ECO:0000269|PubMed:28112729}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Lysosome - Homo sapiens (human);Iron metabolism in placenta;Transferrin endocytosis and recycling;Stimuli-sensing channels;Ion channel transport;Transport of small molecules;TRP channels;Iron uptake and transport
(Consensus)
Recessive Scores
- pRec
- 0.172
Intolerance Scores
- loftool
- 0.270
- rvis_EVS
- -0.93
- rvis_percentile_EVS
- 9.61
Haploinsufficiency Scores
- pHI
- 0.239
- hipred
- Y
- hipred_score
- 0.563
- ghis
- 0.531
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.957
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Mcoln1
- Phenotype
- 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); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system 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); digestive/alimentary phenotype; vision/eye 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); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; muscle phenotype;
Zebrafish Information Network
- Gene name
- mcoln1a
- Affected structure
- cornea
- Phenotype tag
- abnormal
- Phenotype quality
- increased amount
Gene ontology
- Biological process
- adaptive immune response;cation transport;calcium-mediated signaling;transferrin transport;iron ion transmembrane transport;release of sequestered calcium ion into cytosol;protein homotetramerization;calcium ion transmembrane transport;cellular response to calcium ion;cellular response to pH;autophagosome maturation
- Cellular component
- phagocytic cup;lysosome;lysosomal membrane;late endosome;cytosol;plasma membrane;integral component of plasma membrane;endosome membrane;integral component of membrane;phagocytic vesicle membrane;late endosome membrane;cell projection;receptor complex
- Molecular function
- cation channel activity;calcium channel activity;iron ion transmembrane transporter activity;protein binding;lipid binding;NAADP-sensitive calcium-release channel activity;intracellular phosphatidylinositol-3,5-bisphosphate-sensitive cation channel activity;ligand-gated calcium channel activity