MICAL1

microtubule associated monooxygenase, calponin and LIM domain containing 1, the group of LIM domain containing

Basic information

Region (hg38): 6:109444061-109465968

Previous symbols: [ "NICAL" ]

Links

ENSG00000135596 ∙ NCBI:64780 ∙ OMIM:607129 ∙ HGNC:20619 ∙ Uniprot:Q8TDZ2 ∙ 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 MICAL1 gene.

• not provided (690 variants)
• Inborn genetic diseases (76 variants)
• Epilepsy, familial temporal lobe, 1 (4 variants)
• MICAL1-related Lateral temporal epilepsy (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MICAL1 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			3	124	12	139
missense			327	27	17	371
nonsense			10	4		14
start loss						0
frameshift		1	14	6		21
inframe indel			8	1		9
splice donor/acceptor (+/-2bp)			13	1		14
splice region			15	22	1	38
non coding			17	73	15	105
Total	0	1	392	236	44

Variants in MICAL1

This is a list of pathogenic ClinVar variants found in the MICAL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-109444203-C-G			Likely benign (Mar 19, 2022)
6-109444204-CCT-C			Likely pathogenic (Dec 15, 2023)
6-109444212-C-T			Likely benign (Jan 21, 2024)
6-109444215-G-C			Likely benign (Jul 14, 2022)
6-109444223-C-T			Uncertain significance (Apr 09, 2022)
6-109444224-G-A			Likely benign (Mar 31, 2023)
6-109444224-G-C		not specified	Uncertain significance (Dec 07, 2021)
6-109444232-T-C			Uncertain significance (Feb 27, 2023)
6-109444234-C-T			Uncertain significance (Dec 11, 2023)
6-109444235-G-A			Uncertain significance (Feb 20, 2023)
6-109444235-GCTC-G			Uncertain significance (May 08, 2023)
6-109444244-G-A			Uncertain significance (Dec 01, 2023)
6-109444248-G-T			Likely benign (Dec 17, 2023)
6-109444249-C-T			Uncertain significance (Apr 14, 2023)
6-109444250-G-A			Benign (Jan 24, 2024)
6-109444255-A-T		not specified	Uncertain significance (Aug 02, 2021)
6-109444270-T-C			Uncertain significance (Apr 25, 2022)
6-109444275-C-A		not specified	Conflicting classifications of pathogenicity (Dec 21, 2023)
6-109444281-C-T			Benign (Jan 30, 2024)
6-109444284-C-T			Likely benign (Dec 11, 2023)
6-109444285-A-G			Uncertain significance (Sep 13, 2022)
6-109444287-C-T			Likely benign (Aug 17, 2023)
6-109444293-C-T			Likely benign (Mar 31, 2023)
6-109444295-G-A			Likely benign (Jan 19, 2024)
6-109444315-C-T			Uncertain significance (Jul 31, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MICAL1	protein_coding	protein_coding	ENST00000358807	24	21907

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.38e-22	0.555	124965	6	777	125748	0.00312

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.236	655	638	1.03	0.0000407	6846
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00361	0.00361
Ashkenazi Jewish	0.00169	0.00169
East Asian	0.0181	0.0179
Finnish	0.00213	0.00213
European (Non-Finnish)	0.00178	0.00175
Middle Eastern	0.0181	0.0179
South Asian	0.00304	0.00294
Other	0.00196	0.00179

dbNSFP

Source: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.0711
• hipred: N
• hipred_score: 0.463
• ghis: 0.553

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.813

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mical1

Gene ontology

• Biological process: negative regulation of protein phosphorylation;cytoskeleton organization;signal transduction;blood coagulation;sulfur oxidation;actin filament depolymerization;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;oxidation-reduction process;regulation of regulated secretory pathway
• Cellular component: cytoplasm;cytosol;intermediate filament;midbody;intercellular bridge;hippocampal mossy fiber expansion
• 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;SH3 domain binding;Rab GTPase binding;protein kinase binding;metal ion binding;FAD binding