MICOS13

Summary

MICOS13 (mitochondrial contact site and cristae organizing system subunit 13, HGNC:33702) is a protein-coding gene on chromosome 19p13.3, encoding MICOS complex subunit MIC13 (Q5XKP0). Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. It is a selective cancer dependency (DepMap: 14.5% of cell lines).

Involved in cristae formation. Located in mitochondrial crista junction. Part of MICOS complex. Implicated in combined oxidative phosphorylation deficiency 37.

Source: NCBI Gene 125988 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 38 total — 3 pathogenic, 4 likely-pathogenic
• Expression (HPA): Low tissue specificity — highest in skeletal muscle, heart muscle, tongue
• GTEx eGene: eQTL in 10 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 47
• Cancer dependency (DepMap): dependent in 14.5% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.63 (unconstrained)
• MANE Select transcript: NM_205767

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33702
Approved symbol	MICOS13
Name	mitochondrial contact site and cristae organizing system subunit 13
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	QIL1, P117, MIC13, MIC12
Ensembl gene	ENSG00000174917
Ensembl biotype	protein_coding
OMIM	616658
Entrez	125988

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 18 protein_coding, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000309324

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2, TSL 3: 2, TSL 5: 1

ENST00000309324, ENST00000585605, ENST00000587589, ENST00000587950, ENST00000590075, ENST00000590389, ENST00000896351, ENST00000917836, ENST00000983732, ENST00001039812, ENST00001039814, ENST00001039815, ENST00001062553, ENST00001062554, ENST00001062555, ENST00001099779, ENST00001099780, ENST00001099781, ENST00001099782, ENST00001099783, ENST00001099784, ENST00001099785, ENST00001118967, ENST00001125082, ENST00001125083, ENST00001139636

RefSeq mRNA: 3 — MANE Select: NM_205767 NM_001308240, NM_001365761, NM_205767

CCDS: CCDS12143, CCDS77221

Canonical transcript exons

ENST00000309324 — 4 exons

Exon	Start	End
ENSE00001291271	5680458	5680516
ENSE00001313823	5678422	5678648
ENSE00003662989	5679345	5679396
ENSE00003688464	5679586	5679763

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 99.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 60.1557 / max 249.6912, expressed in 1825 samples.

Highest expression (Bgee): apex of heart, testis, atrium auricular region, cardiac atrium, heart left ventricle.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MICOS13 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 10 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

12 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	3.7e-10	-0.43	19:5698270:T:G
Brain Putamen basal ganglia	eqtl	3.8e-05	+1.29	19:6538030:G:A
Brain Substantia nigra	sqtl	6.3e-03	+1.47	19:5513504:G:T
Breast Mammary Tissue	eqtl	6.5e-03	-0.34	19:6148321:C:T
Heart Left Ventricle	eqtl	8.6e-03	+0.31	19:4893009:G:A
Esophagus Mucosa	eqtl	1.7e-02	-0.40	19:6290289:A:G
Brain Caudate basal ganglia	eqtl	2.7e-02	+0.12	19:4889675:T:C
Artery Tibial	eqtl	2.9e-02	-0.07	19:6624891:T:C
Esophagus Mucosa	sqtl	3.8e-02	+0.48	19:5921341:G:A
Skin Sun Exposed Lower leg	eqtl	4.0e-02	+0.11	19:5228318:C:T
Artery Aorta	eqtl	4.6e-02	-0.09	19:6003668:A:C
Pancreas	eqtl	4.7e-02	-0.34	19:6371400:C:T

FANTOM5 promoters

9 alternative TSS:

Promoter ID	TPM avg	Samples expressed
178552	52.1207	1824
178553	2.9627	1591
178551	2.3849	1260
178554	0.8899	661
178555	0.6595	400
208662	0.4544	251
178550	0.4252	209
178557	0.2334	51
178556	0.0251	6

Top tissues by expression

showing 100 of 256 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.26	gold quality
left testis	UBERON:0004533	98.85	gold quality
right atrium auricular region	UBERON:0006631	98.84	gold quality
right testis	UBERON:0004534	98.81	gold quality
cardiac atrium	UBERON:0002081	98.68	gold quality
heart left ventricle	UBERON:0002084	98.68	gold quality
cardiac ventricle	UBERON:0002082	98.59	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.58	gold quality
gastrocnemius	UBERON:0001388	98.37	gold quality
mucosa of transverse colon	UBERON:0004991	98.33	gold quality
anterior cingulate cortex	UBERON:0009835	98.29	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.24	gold quality
left ventricle myocardium	UBERON:0006566	98.21	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.17	gold quality
prefrontal cortex	UBERON:0000451	98.16	gold quality
lower esophagus	UBERON:0013473	98.16	gold quality
heart	UBERON:0000948	98.10	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.10	gold quality
hypothalamus	UBERON:0001898	97.98	gold quality
left coronary artery	UBERON:0001626	97.97	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.97	gold quality
muscle of leg	UBERON:0001383	97.96	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.94	gold quality
tibialis anterior	UBERON:0001385	97.91	gold quality
right frontal lobe	UBERON:0002810	97.90	gold quality
amygdala	UBERON:0001876	97.85	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.84	gold quality
metanephros cortex	UBERON:0010533	97.81	gold quality
adenohypophysis	UBERON:0002196	97.71	gold quality
nucleus accumbens	UBERON:0001882	97.70	gold quality
right lobe of thyroid gland	UBERON:0001119	97.68	gold quality
caudate nucleus	UBERON:0001873	97.68	gold quality
coronary artery	UBERON:0001621	97.66	gold quality
putamen	UBERON:0001874	97.66	gold quality
transverse colon	UBERON:0001157	97.65	gold quality
body of stomach	UBERON:0001161	97.64	gold quality
left adrenal gland cortex	UBERON:0035825	97.59	gold quality
right adrenal gland	UBERON:0001233	97.50	gold quality
left adrenal gland	UBERON:0001234	97.49	gold quality
right coronary artery	UBERON:0001625	97.41	gold quality
mucosa of stomach	UBERON:0001199	97.39	gold quality
ascending aorta	UBERON:0001496	97.39	gold quality
thoracic aorta	UBERON:0001515	97.38	gold quality
popliteal artery	UBERON:0002250	97.38	gold quality
tibial artery	UBERON:0007610	97.38	gold quality
right uterine tube	UBERON:0001302	97.37	gold quality
aorta	UBERON:0000947	97.31	gold quality
left lobe of thyroid gland	UBERON:0001120	97.31	gold quality
esophagus	UBERON:0001043	97.26	gold quality
right adrenal gland cortex	UBERON:0035827	97.23	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.22	gold quality
spinal cord	UBERON:0002240	97.14	gold quality
pituitary gland	UBERON:0000007	97.11	gold quality
lower esophagus mucosa	UBERON:0035834	97.08	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.03	gold quality
omental fat pad	UBERON:0010414	97.03	gold quality
substantia nigra	UBERON:0002038	97.02	gold quality
peritoneum	UBERON:0002358	97.00	gold quality
adult mammalian kidney	UBERON:0000082	96.99	gold quality
tibial nerve	UBERON:0001323	96.99	gold quality
skin of leg	UBERON:0001511	96.98	gold quality
minor salivary gland	UBERON:0001830	96.96	gold quality
descending thoracic aorta	UBERON:0002345	96.95	gold quality
skin of abdomen	UBERON:0001416	96.94	gold quality
right lobe of liver	UBERON:0001114	96.87	gold quality
endocervix	UBERON:0000458	96.84	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.79	gold quality
adrenal cortex	UBERON:0001235	96.78	gold quality
myocardium	UBERON:0002349	96.78	gold quality
heart right ventricle	UBERON:0002080	96.76	gold quality
esophagus mucosa	UBERON:0002469	96.76	gold quality
frontal cortex	UBERON:0001870	96.68	gold quality
ectocervix	UBERON:0012249	96.68	gold quality
left uterine tube	UBERON:0001303	96.53	gold quality
body of pancreas	UBERON:0001150	96.52	gold quality
neocortex	UBERON:0001950	96.45	gold quality
cortex of kidney	UBERON:0001225	96.44	gold quality
colon	UBERON:0001155	96.42	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.41	gold quality
testis	UBERON:0000473	96.34	gold quality
midbrain	UBERON:0001891	96.34	gold quality
thyroid gland	UBERON:0002046	96.34	gold quality
body of uterus	UBERON:0009853	96.28	gold quality
large intestine	UBERON:0000059	96.23	gold quality
kidney epithelium	UBERON:0004819	96.19	gold quality
mouth mucosa	UBERON:0003729	96.12	gold quality
upper lobe of left lung	UBERON:0008952	96.07	gold quality
right ovary	UBERON:0002118	96.06	gold quality
zone of skin	UBERON:0000014	96.01	gold quality
skeletal muscle tissue	UBERON:0001134	95.98	gold quality
forebrain	UBERON:0001890	95.98	gold quality
ileal mucosa	UBERON:0000331	95.96	gold quality
adrenal gland	UBERON:0002369	95.95	gold quality
stromal cell of endometrium	CL:0002255	95.93	gold quality
deltoid	UBERON:0001476	95.92	gold quality
muscle tissue	UBERON:0002385	95.92	gold quality
granulocyte	CL:0000094	95.87	gold quality
right lung	UBERON:0002167	95.83	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.68	gold quality
small intestine	UBERON:0002108	95.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.28

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	262.0	low
Heart muscle	tissue	253.6	medium
Tongue	tissue	174.0
Caudate putamen	tissue	150.7
Frontal cortex	tissue	131.2
Locus coeruleus	tissue	119.5
Pituitary gland	tissue	104.7
Nucleus accumbens	tissue	99.5
Choroid plexus	tissue	96.5
Hippocampus	tissue	92.0	low
Parathyroid gland	tissue	91.3	high
Salivary gland	tissue	89.6	medium
Postcentral gyrus	tissue	88.4
Vagina	tissue	85.5	medium
Pancreas	tissue	81.7	low
Esophagus	tissue	81.6	medium
Duodenum	tissue	73.8	medium
Colon	tissue	71.5	medium
Adipose tissue	tissue	66.6	not detected
Adrenal gland	tissue	64.8	low
Fallopian tube	tissue	63.2	medium
Small intestine	tissue	62.7	medium
Kidney	tissue	60.8	medium
Stomach 1	tissue	57.3	medium
Seminal vesicle	tissue	57.1	medium
Lymph node	tissue	56.5	low
Liver	tissue	55.7	medium
Skin 1	tissue	55.5	low
Testis	tissue	54.0	medium
Thyroid gland	tissue	54.0	medium
Ovary	tissue	53.2	medium
Breast	tissue	53.0	low
Urinary bladder	tissue	51.7	medium
Pons	tissue	51.6
Bone marrow	tissue	50.7	medium
Gallbladder	tissue	50.3	medium
Thalamus	tissue	48.0
Appendix	tissue	45.6	medium
Prostate	tissue	45.2	medium
Superior colliculi	tissue	45.1
Spleen	tissue	42.3	medium
Medulla oblongata	tissue	42.1
Lung	tissue	41.6	medium
Epididymis	tissue	41.4	medium
Cervix	tissue	41.2	medium
Smooth muscle	tissue	40.8	low
Spinal cord	tissue	40.5
Midbrain	tissue	39.5
Putamen	tissue	38.9
Rectum	tissue	38.1	medium
Substantia nigra	tissue	37.6
Hippocampal formation	tissue	36.5
Thymus	tissue	36.1
Septum	tissue	36.1
Cerebral cortex	tissue	35.9	medium
Somatosensory cortex	tissue	35.9
Placenta	tissue	35.5	medium
Motor cortex	tissue	34.9
Basal ganglia	tissue	33.6	medium
Occipital cortex	tissue	33.3

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Mammillary body (133.8), Cerebellar nuclei (131.2), Posterior thalamic nucleus (129.8), Blood vessel (128.3), Spinal trigeminal nucleus, interpolar (121.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting MICOS13 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

3 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-11399	98.71	65.69	869
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-6781-5P	94.61	59.49	155

Functional genomics

gnomAD constraint: pLI 7.93e-08, LOEUF 1.63, missense Z -0.378 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000309324 — one region, missense o/e 1.06. DepMap (CRISPR cell-line fitness): dependent in 14.5% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): KELLY (-1.672), WSU-NHL (-1.293), SIMA (-1.245), RCH-ACV (-1.168), OCI-LY18 (-1.167), NCI-H716 (-1.165), HG-3 (-1.153), COV434 (-1.151), SUM-190PT (-1.119), NCI-H1048 (-1.092), TTC-549 (-1.079), JAR (-1.065), SH-SY5Y (-1.002), RI-1 (-0.991), C-4 II (-0.983).

Literature-anchored findings (GeneRIF, showing 5)

• we identified QIL1 (C19orf70) as a novel conserved MICOS subunit. (PMID:25997101)
• MIC13 has a fundamental role in crista junction formation and that assembly of respiratory chain supercomplexes is independent of mitochondrial cristae shape. (PMID:27479602)
• Mitochondrial hepato-encephalopathy patients were found to be homozygous for the p.(Gly15Glufs*75) variant in the QIL1 . QIL1 deficiency is associated with disassembly of the MICOS complex, aberration of cristae morphology and mitochondrial respiratory dysfunction. (PMID:27485409)
• Taken together, these data provide the first evidence of altered mitochondrial contact site assembly linked with a human mitochondrial disease and confirm a central role for QIL1 in stable mitochondrial contact site complex formation. (PMID:27623147)
• Conserved GxxxG and WN motifs of MIC13 are essential for bridging two MICOS subcomplexes. (PMID:34271005)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	micos13	ENSDARG00000071378
mus_musculus	Micos13	ENSMUSG00000049760
rattus_norvegicus	Micos13	ENSRNOG00000046002

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2442174) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating HDL cholesterol level	1
decreased circulating phosphate level	1
decreased circulating cholesterol level	1
decreased circulating creatinine level	1
decreased blood urea nitrogen level	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	Q2ACH7	99.2%	Diamond
Sus scrofa	A1XQR7	85.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
HSD11B1L	protein-coding	374875
SAFB	protein-coding	6294
SAFB2	protein-coding	9667
TINCR	protein-coding	257000
CATSPERD	protein-coding	257062
RPL36	protein-coding	25873
LONP1	protein-coding	9361
PRR22	protein-coding	163154

Protein

Protein identifiers

MICOS complex subunit MIC13 — Q5XKP0 (reviewed: Q5XKP0)

Alternative names: Protein P117

All UniProt accessions (4): A0A140TA84, A0A140TA86, K7EIR2, Q5XKP0

UniProt curated annotations — full annotation on UniProt →

Function. Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. Constituent of mature MICOS complex, it is required for the formation of cristae junction (CJ) and maintenance of cristae morphology. Required for the incorporation of MICOS10/MIC10 into the MICOS complex.

Subunit / interactions. Component of the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOO/MIC26, MICOS13/MIC13, APOOL/MIC27 and IMMT/MIC60. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex.

Subcellular location. Mitochondrion inner membrane.

Disease relevance. Combined oxidative phosphorylation deficiency 37 (COXPD37) [MIM:618329] An autosomal recessive disorder due to mitochondrial dysfunction and characterized by hypotonia, failure to thrive, progressive neurodegeneration with neurologic deterioration after the first months of life, global developmental delay, as well as liver dysfunction. Some patients may have hypertrophic cardiomyopathy, loss of vision and hearing, and/or seizures. Death in first months or years of life is observed in most patients. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the MICOS complex subunit Mic13 family.

RefSeq proteins (3): NP_001295169, NP_001352690, NP_991330* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026769	Mic13	Family

Pfam: PF15884

UniProt features (5 total): topological domain 2, chain 1, transmembrane region 1, sequence conflict 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5XKP0-F1	86.01	0.45

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes, Congenital disorders of metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria; nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-8949613	Cristae formation	electronic
R-HSA-1592230	Mitochondrial biogenesis	—
R-HSA-1852241	Organelle biogenesis and maintenance	—

MSigDB gene sets: 210 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_CRISTAE_FORMATION, GOBP_INNER_MITOCHONDRIAL_MEMBRANE_ORGANIZATION, GOCC_MITOCHONDRIAL_ENVELOPE, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, RFX1_02, GOBP_MEMBRANE_ORGANIZATION, GOCC_ORGANELLE_MEMBRANE_CONTACT_SITE, GOCC_OUTER_MITOCHONDRIAL_MEMBRANE_PROTEIN_COMPLEX, GOCC_ORGANELLE_INNER_MEMBRANE, GOCC_INNER_MITOCHONDRIAL_MEMBRANE_PROTEIN_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOCC_MITOCHONDRIAL_PROTEIN_CONTAINING_COMPLEX, chr19p13, STAT1_02

GO Biological Process (2): inner mitochondrial membrane organization (GO:0007007), cristae formation (GO:0042407)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (6): SAM complex (GO:0001401), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial crista junction (GO:0044284), MICOS complex (GO:0061617), MIB complex (GO:0140275)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Mitochondrial biogenesis	1
Organelle biogenesis and maintenance	1

GO top-level categories

11 GO namespaces:

Category	Terms
inner mitochondrial membrane protein complex	2
mitochondrial membrane organization	1
inner mitochondrial membrane organization	1
binding	1
mitochondrial outer membrane translocase complex	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial inner membrane	1
organelle membrane contact site	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 9 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
cristae formation	BP	mutant phenotype
MIB complex	CC	high-throughput assay
MICOS complex	CC	direct assay
SAM complex	CC	high-throughput assay
mitochondrial crista junction	CC	direct assay
mitochondrial inner membrane	CC	direct assay
mitochondrion	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,134 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MICOS13	APOOL	Q6UXV4	805
MICOS13	CHCHD6	Q9BRQ6	783
MICOS13	APOO	Q9BUR5	778
MICOS13	CHCHD3	Q9NX63	763
MICOS13	MICOS10	Q5TGZ0	728
MICOS13	IMMT	Q16891	716
MICOS13	SAMM50	Q9Y512	672
MICOS13	DNAJC11	Q9NVH1	619
MICOS13	CHCHD5	Q9BSY4	574
MICOS13	MTX2	O75431	561
MICOS13	CHCHD10	Q8WYQ3	494
MICOS13	B8ZZ87	B8ZZ87	484
MICOS13	CARD19	Q96LW7	482
MICOS13	ZNF48	Q96MX3	479
MICOS13	AFG3L2	Q9Y4W6	470

IntAct

Human interaction partners of MICOS13 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

13 partners by confidence:

Partner	Interaction type	MIscore	Records
ACSF2	physical association	0.560	3
APOC1	physical association	0.560	3
APOC4	physical association	0.560	3
DIABLO	physical association	0.560	3
HSFX1	physical association	0.560	3
PBX3	physical association	0.560	3
RHBDD2	physical association	0.560	3
TEX44	physical association	0.560	3
HLA-A	physical association	0.000	1
PELO	physical association	0.000	1
TNFRSF14	physical association	0.000	1
TSC22D1	physical association	0.000	1
VHL	physical association	0.000	1

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
MIB complex, mitochondrial	12	MTX1, SAMM50, CHCHD3, DNAJC11, MICOS10, MTX2, MTX3, APOO, APOOL, CHCHD6, IMMT, MICOS13
MICOS complex, mitochondrial	7	CHCHD6, IMMT, MICOS10, MICOS13, APOO, APOOL, CHCHD3

Disease & clinical

Genetic variants

Variant evidence for MICOS13: 38 ClinVar records (7 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	4
Uncertain significance	8
Likely benign	15
Benign	1

Top pathogenic / likely-pathogenic (7)

Showing all 7 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
425157	NM_205767.3(MICOS13):c.260-2A>G	Pathogenic	criteria provided, single submitter	2
3703972	NM_205767.3(MICOS13):c.78C>G (p.Tyr26Ter)	Pathogenic	criteria provided, single submitter	1
3126314	NM_205767.3(MICOS13):c.78C>A (p.Tyr26Ter)	Likely pathogenic	criteria provided, single submitter	1
4278449	NM_205767.3(MICOS13):c.162dup (p.Phe55fs)	Likely pathogenic	criteria provided, single submitter	1
4846855	NM_205767.3(MICOS13):c.169C>T (p.Gln57Ter)	Likely pathogenic	criteria provided, single submitter	1
4850746	NM_205767.3(MICOS13):c.150dup (p.Ala51fs)	Likely pathogenic	criteria provided, single submitter	1
619099	NM_205767.3(MICOS13):c.30-1G>A	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore MICOS13’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 297):

Position(s)	Effect	Δscore	Sites
19:5678649	acceptor_loss	1.0000
19:5679584–5679585	donor_loss	1.0000	5
19:5679764–5679765	acceptor_loss	1.0000	5
19:5678649–5678650	acceptor_loss	0.9900	4
19:5679343–5679344	donor_loss	0.9900	4
19:5679397–5679398	acceptor_loss	0.9900	6
19:5679657	donor_gain	0.9900
19:5679772	acceptor_gain	0.9900
19:5679344	donor_loss	0.9800
19:5678651	acceptor_gain	0.9700

AlphaMissense

163 missense substitutions predicted likely pathogenic (of 755 scored), across 63 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
W84	7	0.909	0.966
K14	6	0.843	0.959
P99	6	0.739	0.829
F55	5	0.756	0.891
W110	5	0.754	0.789
N85	5	0.695	0.770
S16	4	0.927	0.987
G19	4	0.911	0.949
S37	4	0.843	0.922
G87	4	0.814	0.912
Y23	4	0.793	0.933
D27	4	0.738	0.872
F11	4	0.720	0.792
Y105	4	0.701	0.764
S34	4	0.692	0.727
G15	3	0.959	0.973
L95	3	0.903	0.920
L30	3	0.847	0.861
L12	3	0.846	0.899
I88	3	0.808	0.830

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:616658 | disease phenotypes: MIM:618329 (Combined oxidative phosphorylation deficiency 37)

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
mitochondrial disease	Definitive	Autosomal recessive
3-methylglutaconic aciduria type 3	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (8 panels, 8 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

8 panels:

Panel	Rating
Fetal anomalies	green
Hypotonic infant	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Mitochondrial disorders	green
Paediatric disorders	green
Possible mitochondrial disorder, nuclear genes	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (3): mitochondrial disease (MONDO:0044970), 3-methylglutaconic aciduria type 3 (MONDO:0009787), combined oxidative phosphorylation deficiency 37 (MONDO:0032679)

HPO phenotypes

47 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000505	Visual impairment
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000817	Reduced eye contact
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001321	Cerebellar hypoplasia
HP:0001347	Hyperreflexia
HP:0001403	Macrovesicular hepatic steatosis
HP:0001408	Bile duct proliferation
HP:0001410	Decreased liver function
HP:0001508	Failure to thrive
HP:0001639	Hypertrophic cardiomyopathy
HP:0001943	Hypoglycemia
HP:0002045	Hypothermia
HP:0002093	Respiratory insufficiency
HP:0002151	Increased circulating lactate concentration
HP:0002313	Spastic paraparesis
HP:0002344	Progressive neurologic deterioration
HP:0002421	Poor head control
HP:0002878	Respiratory failure
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003073	Hypoalbuminemia
HP:0003128	Lactic acidosis
HP:0003348	Hyperalaninemia
HP:0003535	3-Methylglutaconic aciduria
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003676	Progressive
HP:0005484	Secondary microcephaly
HP:0008151	Prolonged prothrombin time
HP:0008936	Axial hypotonia
HP:0011968	Feeding difficulties
HP:0030948	Elevated gamma-glutamyltransferase level
HP:0032794	Myoclonic seizure
HP:0032988	Persistent head lag
HP:0040031	Chorioretinal hyperpigmentation

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C535311	Costeff optic atrophy syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067437 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.77	Kd	169.1	nM	CHEMBL5653589
6.77	ED50	169.1	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149164: Binding affinity to human QIL1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1691	uM

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	decreases reaction, increases reaction, affects binding	1
chloropicrin	increases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	decreases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
MT19c compound	decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cisplatin	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Methotrexate	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Antirheumatic Agents	affects cotreatment, decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652206	Binding	Binding affinity to human QIL1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SG13	HAP1 C19orf70 (-) 1	Cancer cell line	Male
CVCL_SG14	HAP1 C19orf70 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 104 trials:

NCT	Phase	Status	Title
NCT03351998	Phase 4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
NCT00432744	Phase 3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
NCT05162768	Phase 3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT06451757	Phase 3	RECRUITING	KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
NCT02398201	Phase 2	COMPLETED	A Study of Bezafibrate in Mitochondrial Myopathy
NCT02473445	Phase 2	TERMINATED	A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease
NCT02500628	Phase 2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT02805790	Phase 2	COMPLETED	Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
NCT02909400	Phase 2	COMPLETED	The KHENERGY Study
NCT02976038	Phase 2	TERMINATED	Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
NCT03177798	Phase 2	COMPLETED	Mitochondria and Chronic Kidney Disease
NCT03866954	Phase 2	WITHDRAWN	Trial of Erythrocyte Encapsulated Thymidine Phosphorylase In Mitochondrial Neurogastrointestinal Encephalomyopathy
NCT04165239	Phase 2	COMPLETED	The KHENERGYZE Study
NCT04604548	Phase 2	COMPLETED	The KHENEREXT Study
NCT04802707	Phase 2	RECRUITING	Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
NCT04846036	Phase 2	SUSPENDED	The KHENERGYC Study
NCT05650229	Phase 2	RECRUITING	Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease
NCT05972954	Phase 2	COMPLETED	OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)
NCT06017869	Phase 2	RECRUITING	Evaluate the Safety and Therapeutic Effects of a Single Intravenous Infusion (IV) of Autologous CD34+ Cells Enriched With Allogenic Placenta-derived Mitochondria in Patients With a Diagnosis of Pearson Syndrome (PS)
NCT07514338	Phase 2	RECRUITING	Open Label Extension to Assess Long Term Safety and Efficacy of KL1333 in Patients With Primary Mitochondrial Disease
NCT00060515	Phase 1	TERMINATED	RG2133 (2’,3’,5’-Tri-O-Acetyluridine) in Mitochondrial Disease
NCT02348125	Phase 1	UNKNOWN	Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?
NCT02544217	Phase 1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT03888716	Phase 1	COMPLETED	A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
NCT04086329	Phase 1	RECRUITING	Validation of Oxygen Nanosensor in Mitochondrial Myopathy
NCT04643249	Phase 1	COMPLETED	Drug-drug Interaction Study of KL1333 in Healthy Subjects
NCT05241262	Phase 1	RECRUITING	Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels
NCT05569122	Phase 1	RECRUITING	Applying pGz in Mitochondrial Disease
NCT06819683	Phase 1	RECRUITING	Validation of Nanosensor Oxygen Measurement
NCT07258667	Phase 1	NOT_YET_RECRUITING	Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber’s Hereditary Optic Neuropathy
NCT04378075	Phase 2/3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy
NCT01642056	Phase 1/2	COMPLETED	EPI-743 for Metabolism or Mitochondrial Disorders
NCT03384420	Phase 1/2	COMPLETED	A Study to Evaluate the Safety and Therapeutic Effects of Transplantation of MNV-BM-BLD in Pediatric Patients With Pearson Syndrome
NCT06051448	Phase 1/2	COMPLETED	Promoting Resilience in Stress Management (PRISM) and Clinical-focused Narrative (CFN) Pilot in Adults With Primary Mitochondrial Disease (PMD).
NCT01252979	Early Phase 1	COMPLETED	Ketones & Mitochondrial Heteroplasmy
NCT00786539	Not specified	COMPLETED	Mitochondria Inborn Errors of Metabolism and ANT Defects in Mitochondria Diseases
NCT00829270	Not specified	COMPLETED	Economic and Medical Evaluation of the Whole Mitochondrial DNA Screening by Surveyor and Mitochips Techniques
NCT00831948	Not specified	UNKNOWN	Identification of Large-Scale Mutations of POLG Gene by QMPSF in Patients With Mitochondrial DNA Instability.
NCT01001585	Not specified	TERMINATED	Anesthetic Effects in Mitochondrial Disease
NCT01148550	Not specified	SUSPENDED	Longitudinal Study of Mitochondrial Hepatopathies
NCT01264471	Not specified	COMPLETED	Mechanisms of Mitochondrial Defects in Gulf War Syndrome
NCT01301235	Not specified	COMPLETED	Defining 31Phosphorous Magnetic Resonance Spectroscopy Characteristics in Patients With Mitochondrial Myopathy
NCT01370447	Not specified	NO_LONGER_AVAILABLE	EPI-743 for Mitochondrial Respiratory Chain Diseases
NCT01694940	Not specified	RECRUITING	North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC)
NCT01776918	Not specified	COMPLETED	Energy Requirements in Mitochondrial Disease
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01803906	Not specified	ENROLLING_BY_INVITATION	Tissue Sample Study for Mitochondrial Disorders
NCT02000284	Not specified	ACTIVE_NOT_RECRUITING	Mitochondrial Dysfunction in Autism Spectrum Disorder
NCT02053766	Not specified	TERMINATED	Anesthesia in Patients With Mitochondrial Disease
NCT02154711	Not specified	COMPLETED	Magnetic Resonance Imaging (MRI) Muscle Phenotyping in Mitochondrial Disease
NCT02284334	Not specified	COMPLETED	Glycemic Index in Mitochondrial Disease
NCT02311257	Not specified	COMPLETED	Survey on Supplement Use in Mitochondrial Disease
NCT02375438	Not specified	COMPLETED	Nutritional Assessment in Mitochondrial Cytopathy
NCT02678637	Not specified	COMPLETED	Calf Muscle Strength in Mitochondrial Diseases
NCT02745938	Not specified	COMPLETED	GDF-15 as a Biomarker for Mitochondrial Disease
NCT02809170	Not specified	COMPLETED	The Effect of Arginine and Citrulline Supplementation on Endothelial Dysfunction in Mitochondrial Diseases
NCT02920671	Not specified	COMPLETED	Muscle OXPHOS and Nutrient Homeostasis
NCT02985710	Not specified	COMPLETED	Assessment of Small Fiber Neuropathy in Rare Diseases Using Sudoscan
NCT03048617	Not specified	COMPLETED	An Observational Study of Patients With Primary Mitochondrial Disease (SPIMM-300)
NCT03213067	Not specified	COMPLETED	Mitochondrial and Microbiota Relationship

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MICOS13 across ~30M SureChEMBL compounds — explore on Sugi Predict.