MICU2

Summary

MICU2 (mitochondrial calcium uptake 2, HGNC:31830) is a protein-coding gene on chromosome 13q12.11, encoding Calcium uptake protein 2, mitochondrial (Q8IYU8). Calcium sensor of the mitochondrial calcium uniporter (MCU) channel, which senses calcium level via its EF-hand domains.

Enables several functions, including calcium channel regulator activity; calcium ion sensor activity; and protein heterodimerization activity. Involved in calcium import into the mitochondrion; cellular response to calcium ion; and negative regulation of mitochondrial calcium ion concentration. Located in mitochondrial intermembrane space. Part of uniplex complex. Is active in mitochondrial inner membrane.

Source: NCBI Gene 221154 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Limited, ClinGen)
• GWAS associations: 21
• Clinical variants (ClinVar): 78 total
• MANE Select transcript: NM_152726

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31830
Approved symbol	MICU2
Name	mitochondrial calcium uptake 2
Location	13q12.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000165487
Ensembl biotype	protein_coding
OMIM	610632
Entrez	221154

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000382374, ENST00000460488, ENST00000468222, ENST00000469058, ENST00000476895, ENST00000478700, ENST00000479790, ENST00000480341, ENST00000903401, ENST00000903402, ENST00000903403, ENST00000903404, ENST00000903405, ENST00000903406, ENST00000937097, ENST00000954298

RefSeq mRNA: 1 — MANE Select: NM_152726 NM_152726

CCDS: CCDS9297

Canonical transcript exons

ENST00000382374 — 12 exons

Exon	Start	End
ENSE00001093547	21502926	21503097
ENSE00001260786	21496052	21496160
ENSE00001835008	21492691	21493353
ENSE00001873874	21603939	21604170
ENSE00003478066	21514353	21514418
ENSE00003516814	21521245	21521327
ENSE00003525560	21539657	21539688
ENSE00003548202	21566797	21566944
ENSE00003582781	21522603	21522650
ENSE00003631284	21539302	21539377
ENSE00003635266	21495161	21495318
ENSE00003653044	21510004	21510101

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 98.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.4595 / max 270.0191, expressed in 1821 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136391	42.4595	1821

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	98.00	gold quality
heart right ventricle	UBERON:0002080	97.57	gold quality
renal medulla	UBERON:0000362	97.18	gold quality
pigmented layer of retina	UBERON:0001782	96.94	gold quality
cerebellar hemisphere	UBERON:0002245	96.86	gold quality
cerebellar cortex	UBERON:0002129	96.81	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.74	gold quality
nephron tubule	UBERON:0001231	96.52	gold quality
germinal epithelium of ovary	UBERON:0001304	96.14	gold quality
myocardium	UBERON:0002349	96.14	gold quality
left ventricle myocardium	UBERON:0006566	96.01	gold quality
epithelium of nasopharynx	UBERON:0001951	95.97	gold quality
biceps brachii	UBERON:0001507	95.95	gold quality
superior surface of tongue	UBERON:0007371	95.77	gold quality
jejunum	UBERON:0002115	95.68	gold quality
cerebellum	UBERON:0002037	95.66	gold quality
colonic mucosa	UBERON:0000317	95.65	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.63	gold quality
calcaneal tendon	UBERON:0003701	95.62	gold quality
oral cavity	UBERON:0000167	95.57	gold quality
jejunal mucosa	UBERON:0000399	95.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.55	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.55	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.37	gold quality
adrenal tissue	UBERON:0018303	95.32	gold quality
body of tongue	UBERON:0011876	95.30	gold quality
metanephros	UBERON:0000081	95.24	gold quality
bronchial epithelial cell	CL:0002328	95.18	gold quality
skin of hip	UBERON:0001554	95.17	gold quality
kidney epithelium	UBERON:0004819	95.17	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.99

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): YY1

miRNA regulators (miRDB)

30 targeting MICU2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-5590-5P	98.81	68.78	969
HSA-MIR-3149	98.77	67.13	1639
HSA-MIR-5094	98.63	67.11	1062
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-15B-3P	97.85	66.68	974
HSA-MIR-1231	95.10	65.63	663

Literature-anchored findings (GeneRIF, showing 13)

• The results identify MICU2 as a new component of the uniporter complex that may contribute to the tissue-specific regulation of this channel. (PMID:23409044)
• regulation of MCU-mediated mitochondrial calcium handling (PMID:23409044)
• Expression of MICU2 mutants lacking functional Ca2+-binding sites leads to a striking loss of Ca2+ uptake in HEK293 cells. (PMID:24503055)
• MICU1 and MICU2 have roles in tuning the mitochondrial Ca2+ uniporter by exerting opposite effects on MCU activity (PMID:24560927)
• study concludes that cooperative, high-affinity interaction of the MICU1-MICU2 complex with Ca(2+) serves as an on-off switch, leading to a tightly controlled channel, capable of responding directly to cytosolic Ca(2+) signals (PMID:28615291)
• This is the first demonstration of MICU2 deficiency in humans, which we suggest causes a distinct neurodevelopmental phenotype secondary to impaired mitochondrial calcium uniporter-mediated regulation of intracellular calcium homeostasis. (PMID:29053821)
• MICU2 expression in the heart tissues from patients with ventricular hypertrophy. (PMID:29073106)
• MICU2 restricts spatial crosstalk between InsP3R and MCU channels by regulating threshold and gain of MICU1-mediated inhibition and activation of MCU. (PMID:29241542)
• multiple crystal structures of MICU2 and MICU3 from Homo sapiens, were determined. (PMID:30699349)
• Structures reveal gatekeeping of the mitochondrial Ca(2+) uniporter by MICU1-MICU2. (PMID:32667285)
• The structure of the MICU1-MICU2 complex unveils the regulation of the mitochondrial calcium uniporter. (PMID:32790952)
• Mechanisms of EMRE-Dependent MCU Opening in the Mitochondrial Calcium Uniporter Complex. (PMID:33296646)
• Mitochondrial clearance of calcium facilitated by MICU2 controls insulin secretion. (PMID:33932586)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	micu2	ENSDARG00000009939
mus_musculus	Micu2	ENSMUSG00000021973
rattus_norvegicus	Micu2	ENSRNOG00000011168
caenorhabditis_elegans		WBGENE00008345

Paralogs (2): MICU1 (ENSG00000107745), MICU3 (ENSG00000155970)

Protein

Protein identifiers

Calcium uptake protein 2, mitochondrial — Q8IYU8 (reviewed: Q8IYU8)

Alternative names: EF-hand domain-containing family member A1

All UniProt accessions (3): A0A0A0MTD5, A0A0S2Z6V5, Q8IYU8

UniProt curated annotations — full annotation on UniProt →

Function. Calcium sensor of the mitochondrial calcium uniporter (MCU) channel, which senses calcium level via its EF-hand domains. MICU1 and MICU2 form a disulfide-linked heterodimer that stimulates and inhibits MCU activity, depending on the concentration of calcium. At low calcium levels, MICU1 occludes the pore of the MCU channel, preventing mitochondrial calcium uptake. At higher calcium levels, calcium-binding to MICU1 and MICU2 induces a conformational change that weakens MCU-MICU1 interactions and moves the MICU1-MICU2 heterodimer away from the pore, allowing calcium permeation through the MCU channel.

Subunit / interactions. Heterodimer; disulfide-linked; heterodimerizes with MICU1. Component of the uniplex complex, composed of MCU, EMRE/SMDT1, MICU1 and MICU2 in a 4:4:1:1 stoichiometry.

Subcellular location. Mitochondrion intermembrane space. Mitochondrion inner membrane.

Domain organisation. EF-hand domains 1 and 4 have high affinity for calcium and act as sensors of mitochondrial matrix calcium levels. EF-hand domains 2 and 3 are degenerate.

Similarity. Belongs to the MICU1 family. MICU2 subfamily.

RefSeq proteins (1): NP_689939* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR039800	MICU1/2/3	Family

UniProt features (64 total): helix 19, mutagenesis site 13, binding site 11, strand 7, domain 4, turn 4, transit peptide 1, chain 1, modified residue 1, disulfide bond 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
6IIH	X-RAY DIFFRACTION	1.96
6LB7	X-RAY DIFFRACTION	2.1
6AGH	X-RAY DIFFRACTION	2.74
6LE5	X-RAY DIFFRACTION	3.1
6XQO	ELECTRON MICROSCOPY	3.1
6WDN	ELECTRON MICROSCOPY	3.2
6LB8	X-RAY DIFFRACTION	3.28
6XQN	ELECTRON MICROSCOPY	3.3
6K7Y	ELECTRON MICROSCOPY	3.6
6WDO	ELECTRON MICROSCOPY	3.6
6XJV	ELECTRON MICROSCOPY	4.17
6XJX	ELECTRON MICROSCOPY	4.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYU8-F1	75.75	0.38

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (11): 193; 196; 375; 377; 379; 381; 386; 185; 187; 189; 191

Post-translational modifications (1): 205

Disulfide bonds (1): 413

Mutagenesis-validated functional residues (13):

Position	Phenotype
107	does not affect its ability to regulate the activity of mcu; when associated with 120-e-e-121 and r-154.
120–121	does not affect its ability to regulate the activity of mcu; when associated with e-107 and r-154.
154	does not affect its ability to regulate the activity of mcu; when associated with e-107 and 120-e-e-121.
172	does not affect interaction with micu1.
185	abolishes mitochondrial ca(2+) uptake; when associated with a-375 and a-386. in ef1(mut); decreased calcium-binding and
196	in ef1(mut); decreased calcium-binding and abolished ability to interact with micu1 when associated with a-185.
206	does not affect interaction with micu2.
329	does not affect interaction with micu1.
336	decreased interaction with micu1.
352	abolished interaction with micu1.
352	abilished interaction with micu1 and ability to regulate the activity of mcu.
375	abolishes mitochondrial ca(2+) uptake; when associated with a-185 and a-386.
386	abolishes mitochondrial ca(2+) uptake; when associated with a-185 and a-375.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-8949215	Mitochondrial calcium ion transport
R-HSA-8949664	Processing of SMDT1
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-382551	Transport of small molecules
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 134 (showing top): GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_RESPONSE_TO_METAL_ION, GOBP_MITOCHONDRIAL_CALCIUM_ION_HOMEOSTASIS, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOCC_MITOCHONDRIAL_ENVELOPE, SCHLOSSER_SERUM_RESPONSE_DN, GOBP_CELLULAR_RESPONSE_TO_CALCIUM_ION, GOBP_MONOATOMIC_ION_HOMEOSTASIS, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, GOBP_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, ACEVEDO_LIVER_CANCER_UP, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_RESPONSE_TO_CALCIUM_ION, TGGAAA_NFAT_Q4_01, GOCC_ORGANELLE_INNER_MEMBRANE

GO Biological Process (6): mitochondrial calcium ion transmembrane transport (GO:0006851), calcium import into the mitochondrion (GO:0036444), mitochondrial calcium ion homeostasis (GO:0051560), positive regulation of mitochondrial calcium ion concentration (GO:0051561), negative regulation of mitochondrial calcium ion concentration (GO:0051562), cellular response to calcium ion (GO:0071277)

GO Molecular Function (5): calcium channel regulator activity (GO:0005246), calcium ion binding (GO:0005509), protein heterodimerization activity (GO:0046982), calcium ion sensor activity (GO:0061891), protein binding (GO:0005515)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), calcium channel complex (GO:0034704), uniplex complex (GO:1990246), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Transport of small molecules	1
Mitochondrial calcium ion transport	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrial calcium ion homeostasis	2
calcium ion transmembrane transport	1
mitochondrial calcium ion transmembrane transport	1
intercellular transport	1
mitochondrion	1
intracellular calcium ion homeostasis	1
response to calcium ion	1
cellular response to metal ion	1
calcium channel activity	1
ion channel regulator activity	1
metal ion binding	1
protein dimerization activity	1
calcium ion binding	1
metal ion sensor activity	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial envelope	1
organelle envelope lumen	1
cation channel complex	1
calcium channel complex	1
inner mitochondrial membrane protein complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

884 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MICU2	SMDT1	Q9H4I9	999
MICU2	MCUR1	Q96AQ8	998
MICU2	MCUB	Q9NWR8	998
MICU2	MCU	Q8NE86	995
MICU2	MICU1	Q9BPX6	988
MICU2	MICU3	Q86XE3	973
MICU2	SLC25A23	Q9BV35	911
MICU2	VDAC1	P21796	776
MICU2	SLC8B1	Q6J4K2	775
MICU2	FGF20	Q9NP95	767
MICU2	LETM1	O95202	764
MICU2	FGF9	P31371	762
MICU2	ITPR3	Q14573	729
MICU2	ITPR1	Q14643	719
MICU2	CHCHD4	Q8N4Q1	653

IntAct

95 interactions, top by confidence:

A	B	Type	Score
MICU2	MICU1	psi-mi:“MI:0915”(physical association)	0.780
MICU1	MICU2	psi-mi:“MI:0914”(association)	0.780
MICU1	MICU2	psi-mi:“MI:0915”(physical association)	0.780
RANBP6	SLC27A2	psi-mi:“MI:0914”(association)	0.640
CHCHD4	SSNA1	psi-mi:“MI:0914”(association)	0.640
KLHL22	METTL15	psi-mi:“MI:0914”(association)	0.640
BPNT1	GTPBP10	psi-mi:“MI:0914”(association)	0.530
TRIM44	ODAD3	psi-mi:“MI:0914”(association)	0.530
SPACA1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
DCAF11	GNPAT	psi-mi:“MI:0914”(association)	0.530
ATG7	GFER	psi-mi:“MI:0914”(association)	0.530
MCU	MICU2	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
ARMC6	SLC27A2	psi-mi:“MI:0914”(association)	0.530
PON1	PON3	psi-mi:“MI:0914”(association)	0.530
PYCR3	RPL23	psi-mi:“MI:0914”(association)	0.530
SMDT1	MICU2	psi-mi:“MI:0915”(physical association)	0.490
HTRA2	HAX1	psi-mi:“MI:2364”(proximity)	0.420
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350

BioGRID (137): MICU2 (Affinity Capture-MS), ASH2L (Affinity Capture-MS), MICU1 (Affinity Capture-MS), ACOX3 (Affinity Capture-MS), CSNK1E (Affinity Capture-MS), CSNK1D (Affinity Capture-MS), GAPVD1 (Affinity Capture-MS), SMAP1 (Affinity Capture-MS), KIAA1217 (Affinity Capture-MS), MICU2 (Affinity Capture-MS), MICU1 (Affinity Capture-MS), ACOX3 (Affinity Capture-MS), KLHL22 (Affinity Capture-MS), SMAP1 (Affinity Capture-MS), MICU2 (Affinity Capture-MS)

ESM2 similar proteins: A0A060LAL9, A0A097ZPE6, A0A1I9R3Y5, A2VEI2, A2XVG1, A8B479, A8WQT4, B3H7A9, F4I1L3, G1JSL4, H2E7T7, O22585, O22788, O45228, O64407, O65015, O81270, P10538, P16098, Q0KHU5, Q19337, Q28C60, Q2QRX6, Q43727, Q5QIT3, Q5R8Y6, Q5Z8Y4, Q66HG5, Q6DCK1, Q7FAX1, Q7JW12, Q8CD10, Q8IYU8, Q8VZQ4, Q95PZ2, Q99805, Q99P63, Q9CAB7, Q9CAB8, Q9D5U0

Diamond homologs: A0A8I6A2H6, Q86XE3, Q8CD10, Q8IYU8, Q99P63, Q9CTY5, A2VEI2, A4IG32, A8WQT4, B1H2N3, D2HZB0, Q0IIL1, Q4R518, Q6P6Q9, Q8VCX5, Q95PZ2, Q9BPX6, Q9SZ45, F1LX07

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MICU2	“form complex”	MCU_MICUB_variant	binding
MICU2	“form complex”	MCU_MICU2_variant	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 119 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Processing of SMDT1	5	46.0×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

78 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2437 predictions. Top by Δscore:

Variant	Effect	Δscore
13:21493350:GTACC:G	acceptor_loss	1.0000
13:21493352:ACCT:A	acceptor_loss	1.0000
13:21493353:CCTG:C	acceptor_loss	1.0000
13:21493362:C:CT	acceptor_gain	1.0000
13:21493362:C:T	acceptor_gain	1.0000
13:21495314:CTCCG:C	acceptor_gain	1.0000
13:21495315:TCCG:T	acceptor_gain	1.0000
13:21495316:CCG:C	acceptor_gain	1.0000
13:21495316:CCGC:C	acceptor_gain	1.0000
13:21495317:CG:C	acceptor_gain	1.0000
13:21495317:CGC:C	acceptor_gain	1.0000
13:21495319:C:CC	acceptor_gain	1.0000
13:21496159:CT:C	acceptor_gain	1.0000
13:21496161:C:CC	acceptor_gain	1.0000
13:21510000:TTAC:T	donor_loss	1.0000
13:21510001:TAC:T	donor_loss	1.0000
13:21510002:A:C	donor_loss	1.0000
13:21510098:CTTC:C	acceptor_gain	1.0000
13:21510100:TCC:T	acceptor_loss	1.0000
13:21510102:C:CC	acceptor_gain	1.0000
13:21510103:T:A	acceptor_loss	1.0000
13:21514348:CATA:C	donor_loss	1.0000
13:21514349:ATAC:A	donor_loss	1.0000
13:21514350:TA:T	donor_loss	1.0000
13:21514351:A:AG	donor_loss	1.0000
13:21514352:C:A	donor_loss	1.0000
13:21521238:CACTT:C	donor_loss	1.0000
13:21521239:ACTTA:A	donor_loss	1.0000
13:21521240:CTTAC:C	donor_loss	1.0000
13:21521241:TTACC:T	donor_loss	1.0000

AlphaMissense

2885 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:21502999:A:G	L287P	0.998
13:21495312:A:G	F350S	0.997
13:21566829:A:G	F109S	0.997
13:21495248:A:C	F371L	0.996
13:21495248:A:T	F371L	0.996
13:21495250:A:G	F371L	0.996
13:21503055:G:C	F268L	0.996
13:21503055:G:T	F268L	0.996
13:21503057:A:G	F268L	0.996
13:21495216:A:G	L382P	0.995
13:21495216:A:T	L382H	0.995
13:21495239:A:C	F374L	0.995
13:21495239:A:T	F374L	0.995
13:21495241:A:G	F374L	0.995
13:21495252:A:T	V370D	0.995
13:21503011:A:G	F283S	0.995
13:21503056:A:G	F268S	0.995
13:21495201:A:G	F387S	0.994
13:21496060:A:T	V345D	0.994
13:21496141:A:G	F318S	0.994
13:21503003:A:G	W286R	0.994
13:21503003:A:T	W286R	0.994
13:21521299:A:C	F181L	0.994
13:21521299:A:T	F181L	0.994
13:21521301:A:G	F181L	0.994
13:21522617:A:G	L167P	0.994
13:21566876:A:C	F93L	0.994
13:21566876:A:T	F93L	0.994
13:21566878:A:G	F93L	0.994
13:21566885:G:C	F90L	0.994

dbSNP variants (sampled 300 via entrez): RS1000007474 (13:21493412 T>C,G), RS1000110671 (13:21576462 T>C), RS1000190205 (13:21538009 T>C), RS1000201238 (13:21546132 A>T), RS1000216648 (13:21529465 G>C), RS1000258202 (13:21525172 T>C), RS1000289251 (13:21499416 C>T), RS1000394077 (13:21517989 A>G), RS1000394234 (13:21588040 G>C), RS1000401321 (13:21501191 T>C), RS1000405153 (13:21603685 G>A,T), RS1000430748 (13:21562931 T>A,C), RS1000451708 (13:21598229 T>C), RS1000452272 (13:21501348 T>C), RS1000472243 (13:21588254 T>G)

Disease associations

OMIM: gene MIM:610632 | disease phenotypes:

GenCC curated gene-disease

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mitochondrial disease	Limited	AR

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST002456_7	PR segment duration	3.000000e-10
GCST007045_37	PR interval	3.000000e-24
GCST007226_3	PR interval	7.000000e-12
GCST009391_1799	Metabolite levels	6.000000e-08
GCST009391_1882	Metabolite levels	3.000000e-06
GCST009391_1891	Metabolite levels	2.000000e-06
GCST010321_145	PR interval	1.000000e-51
GCST010796_3876	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-11
GCST010796_3877	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-10
GCST010796_3878	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-09
GCST010796_3879	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_3917	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-13
GCST010796_3918	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-12
GCST010796_3919	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-11
GCST010796_3920	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-11
GCST010796_3921	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-12
GCST010796_3922	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-11
GCST010796_3923	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-11
GCST010796_3924	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-11
GCST010796_3925	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-12
GCST011010_21	Electrocardiographic traits (multivariate)	4.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005095	PR segment
EFO:0004462	PR interval
EFO:0010529	ribose-5-phosphate measurement
EFO:0010530	ribulose-5-phosphate measurement
EFO:0010414	triacylglycerol 52:2 measurement
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other ic — Mitochondrial calcium uniporter (MCU) complex

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylselenic acid	decreases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
manganese chloride	increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
(+)-JQ1 compound	increases expression	1
MT19c compound	increases expression	1
Temozolomide	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression	1
Urethane	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8QL	Ubigene HCT 116 MICU2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.