MICU2

mitochondrial calcium uptake 2, the group of EF-hand domain containing

Basic information

Region (hg38): 13:21492691-21604181

Previous symbols: [ "EFHA1" ]

Links

ENSG00000165487 ∙ NCBI:221154 ∙ OMIM:610632 ∙ HGNC:31830 ∙ Uniprot:Q8IYU8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial disease (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MICU2 gene.

• not_specified (52 variants)
• not_provided (5 variants)
• MICU2-related_disorder (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MICU2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000152726.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense			46	7		53
nonsense			1	1		2
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	48	9	0

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MICU2	protein_coding	protein_coding	ENST00000382374	12	111518

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.72e-21	0.000576	124856	2	890	125748	0.00355

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.311	234	221	1.06	0.0000109	2844
Missense in Polyphen		50	62.574	0.79906		846
Synonymous	-1.27	90	75.9	1.19	0.00000372	766
Loss of Function	-0.515	29	26.2	1.11	0.00000140	310

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00686	0.00676
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.000503	0.000489
Finnish	0.000374	0.000370
European (Non-Finnish)	0.00551	0.00547
Middle Eastern	0.000503	0.000489
South Asian	0.00147	0.00144
Other	0.00447	0.00441

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Key regulator of mitochondrial calcium uniporter (MCU) required to limit calcium uptake by MCU when cytoplasmic calcium is low (PubMed:24503055, PubMed:24560927, PubMed:26903221). MICU1 and MICU2 form a disulfide-linked heterodimer that stimulate and inhibit MCU activity, depending on the concentration of calcium (PubMed:24560927). MICU2 acts as a gatekeeper of MCU that senses calcium level via its EF-hand domains: prevents channel opening at resting calcium, avoiding energy dissipation and cell-death triggering (PubMed:24560927). {ECO:0000269|PubMed:24503055, ECO:0000269|PubMed:24560927, ECO:0000269|PubMed:26387864, ECO:0000269|PubMed:26903221}.
• Pathway: Transport of small molecules;Mitochondrial calcium ion transport;Processing of SMDT1 (Consensus)

Recessive Scores

• pRec: 0.101

Intolerance Scores

• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.96

Haploinsufficiency Scores

• pHI: 0.507
• hipred: N
• hipred_score: 0.177
• ghis: 0.567

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Micu2
• Phenotype: cellular phenotype; muscle 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); 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)

Gene ontology

• Biological process: mitochondrial calcium ion transmembrane transport;calcium import into the mitochondrion;mitochondrial calcium ion homeostasis;positive regulation of mitochondrial calcium ion concentration;negative regulation of mitochondrial calcium ion concentration
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial intermembrane space;calcium channel complex;uniplex complex
• Molecular function: calcium ion binding;protein binding;protein heterodimerization activity