MICAL1
protein-codingmicrotubule associated monooxygenase, calponin and LIM domain containing 1, the group of LIM domain containing
Gene summary
This gene encodes an enzyme that oxidizes methionine residues on actin, thereby promoting depolymerization of actin filaments. This protein interacts with and regulates signalling by NEDD9/CAS-L (neural precursor cell expressed, developmentally down-regulated 9). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]
- NICAL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~21.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005027
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0010898
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MICAL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022765.4. 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 | 11 | 227 | 11 | 249 | ||
| missense | 2 | 590 | 49 | 13 | 654 | |
| nonsense | 1 | 15 | 8 | 1 | 25 | |
| start loss | 0 | |||||
| frameshift | 2 | 17 | 23 | 1 | 43 | |
| splice donor/acceptor (+/-2bp) | 1 | 28 | 1 | 30 | ||
| Total | 1 | 5 | 661 | 308 | 26 | 1001 |
Highest pathogenic variant AF is 0.00009231905
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_073602.3 | 24 | MANE Select | |
| Ensembl | ENSP00000351664.3 | 24 | MANE Select | |
| RefSeq | NP_001152763.1 | 23 | Standard | |
| RefSeq | NP_001273542.1 | 25 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of protein phosphorylation
- cytoskeleton organization
- signal transduction
- blood coagulation
- sulfur oxidation
Molecular Function
- actin binding
- monooxygenase activity
- protein binding
- NAD(P)H oxidase activity
- oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen
Cellular Component
- cytoplasm
- cytosol
- intermediate filament
- midbody
- intercellular bridge
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000358807
- Coding exons
- 24
- Length
- 21907
- Individuals with no LoFs
- 124965
- Homozygous LoFs
- 6
- Heterozygous LoFs
- 777
- Defined
- 125748
- p
- 0.00312
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.236 | 655 | 638 | 1.03 | 0.0000407 | 6846 |
| Missense (PolyPhen) | 235 | 221.29 | 1.0619 | 2516 | ||
| Synonymous | 0.321 | 250 | 257 | 0.975 | 0.0000151 | 2216 |
| Loss of Function | 2.09 | 43 | 60.5 | 0.710 | 0.00000341 | 604 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0017 | 0.0017 | notable |
| Latino/Admixed American | 0.0019 | 0.0019 | notable |
| Ashkenazi Jewish | 0.0017 | 0.0017 | notable |
| East Asian | 0.018 | 0.018 | notable |
| Finnish | 0.0021 | 0.0021 | notable |
| European (Non-Finnish) | 0.0018 | 0.0018 | notable |
| South Asian | 0.0030 | 0.0029 | notable |
| Other | 0.0020 | 0.0018 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization (By similarity). In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2) (PubMed:21864500, PubMed:26845023). Acts as a cytoskeletal regulator that connects NEDD9 to intermediate filaments. Also acts as a negative regulator of apoptosis via its interaction with STK38 and STK38L; acts by antagonizing STK38 and STK38L activation by MST1/STK4. Involved in regulation of lamina-specific connectivity in the nervous system such as the development of lamina-restricted hippocampal connections. Through redox regulation of the actin cytoskeleton controls the intracellular distribution of secretory vesicles containing L1/neurofascin/NgCAM family proteins in neurons, thereby regulating their cell surface levels (By similarity). May act as Rab effector protein and play a role in vesicle trafficking. {ECO:0000250|UniProtKB:Q8VDP3, ECO:0000269|PubMed:18305261, ECO:0000269|PubMed:21864500, ECO:0000269|PubMed:26845023, ECO:0000269|PubMed:28230050, ECO:0000305, ECO:0000305|PubMed:27552051}.;
Recessive Scores
- pRec
- 0.102
Intolerance Scores
- LoFtool
- 0.878
- RVIS EVS
- -0.78
- RVIS percentile EVS
- 12.64
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.813
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |