MICAL2

protein-coding

microtubule associated monooxygenase, calponin and LIM domain containing 2, the group of MicroRNA protein coding host genes|LIM domain containing

Gene summary

The protein encoded by this gene is a monooxygenase that enhances depolymerization of F-actin and is therefore involved in cytoskeletal dynamics. The encoded protein is a regulator of the SRF signaling pathway. Increased expression of this gene has been associated with cancer progression and metastasis. [provided by RefSeq, Oct 2016]

Previous symbols:

MICALCL

MANE transcript

NM_001282663.2

Inheritance

—

ClinVar variants

U:205B:13

Top phenotype

Breast ductal adenocarcinoma

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr11:12,094,008-12,359,144

External References & Databases

Ensembl (ENSG00000133816)

Transcript & Mutation Effects

hg38 • Region Span ~265.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MICAL2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 198

not providedTotal: 11

Breast ductal adenocarcinomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001282663.2. 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			1 clinvar	2 clinvar	1 clinvar	4
missense			199 clinvar	7 clinvar	3 clinvar	209
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	205	9	4	218

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 137 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001282663.2	RefSeq	NP_001269592.1	25	MANE Select
ENST00000683283.1	Ensembl	ENSP00000507067.1	25	MANE Select
NM_001282664.1	RefSeq	NP_001269593.1	24	Standard
NM_001282665.1	RefSeq	NP_001269594.1	21	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

heart looping
cytoskeleton organization
heart development
positive regulation of transcription via serum response element binding
sulfur oxidation

Molecular Function

actin binding
NAD(P)H oxidase activity
oxidoreductase 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
NADPH:sulfur oxidoreductase activity

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000256194
Coding exons: 25
Length: 169792
Individuals with no LoFs: 123496
Homozygous LoFs: 24
Heterozygous LoFs: 2228
Defined: 125748
p: 0.00899

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.793	612	670	0.914	0.0000409	7362
Missense (PolyPhen)		224	302.28	0.74104		3352
Synonymous	-1.54	300	268	1.12	0.0000168	2206
Loss of Function	3.49	29	57.6	0.503	0.00000290	670

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0034	0.0034	notable
Latino/Admixed American	0.0013	0.0013	notable
Ashkenazi Jewish	0.0031	0.0031	notable
East Asian	0.00027	0.00027	rare
Finnish	0.0069	0.0070	notable
European (Non-Finnish)	0.017	0.017	notable
South Asian	0.0014	0.0013	notable
Other	0.0071	0.0070	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Nuclear 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 (PubMed:24440334). In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2) (By similarity). Acts as a key regulator of the SRF signaling pathway elicited by nerve growth factor and serum: mediates oxidation and subsequent depolymerization of nuclear actin, leading to increase MKL1/MRTF-A presence in the nucleus and promote SRF:MKL1/MRTF-A-dependent gene transcription. Does not activate SRF:MKL1/MRTF-A through RhoA (PubMed:24440334). {ECO:0000250|UniProtKB:Q8TDZ2, ECO:0000269|PubMed:24440334}.;

Recessive Scores

pRec: 0.103

Intolerance Scores

RVIS EVS: 0.55
RVIS percentile EVS: 81.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.151

Gene Damage Prediction

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