IMMT

Summary

IMMT (inner membrane mitochondrial protein, HGNC:6047) is a protein-coding gene on chromosome 2p11.2, encoding MICOS complex subunit MIC60 (Q16891). 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.

Enables RNA binding activity. Involved in cristae formation. Located in mitochondrial inner membrane. Part of MICOS complex.

Source: NCBI Gene 10989 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 132 total
• GTEx eGene: eQTL in 45 tissues, sQTL in 11 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.67 (unconstrained)
• MANE Select transcript: NM_006839
• Interaction hub: 2,674 STRING partners (top 3% of genes corpus-wide)
• Notable: 132 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6047
Approved symbol	IMMT
Name	inner membrane mitochondrial protein
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Aliases	P87, P89, HMP, MINOS2, Mic60, MICOS60
Ensembl gene	ENSG00000132305
Ensembl biotype	protein_coding
OMIM	600378
Entrez	10989

Gene structure

Transcript identifiers

Ensembl transcripts: 81 — 53 protein_coding, 24 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000410111

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 3, TSL 4: 1, TSL 5: 3

ENST00000410111, ENST00000254636, ENST00000409051, ENST00000409258, ENST00000419070, ENST00000442664, ENST00000449247, ENST00000460081, ENST00000474969, ENST00000486633, ENST00000490238, ENST00000910384, ENST00000910385, ENST00000910386, ENST00000910387, ENST00000910388, ENST00000923521, ENST00000923522, ENST00000923523, ENST00000962805, ENST00000962806, ENST00000962807, ENST00000962808, ENST00000962809, ENST00000962810, ENST00000962811, ENST00000962812, ENST00000962813, ENST00000962814, ENST00000962815, ENST00000962816, ENST00000962817, ENST00000962818, ENST00000962819, ENST00000962820, ENST00000962821, ENST00000962822, ENST00000962823, ENST00000962824, ENST00000962825, ENST00000962826, ENST00000962827, ENST00000962828, ENST00000962829, ENST00000962830, ENST00000962831, ENST00000962832, ENST00000962833, ENST00001006999, ENST00001007000, ENST00001007001, ENST00001020707, ENST00001020708, ENST00001020709, ENST00001020710, ENST00001020711, ENST00001020712, ENST00001020713, ENST00001020714, ENST00001020715, ENST00001020716, ENST00001020717, ENST00001020718, ENST00001020719, ENST00001020720, ENST00001020721, ENST00001020723, ENST00001105756, ENST00001115492, ENST00001115493, ENST00001115494, ENST00001115495, ENST00001115496, ENST00001115497, ENST00001127584, ENST00001127585, ENST00001127586, ENST00001127587, ENST00001127588, ENST00001127589, ENST00001140155

RefSeq mRNA: 52 — MANE Select: NM_006839 NM_001100169, NM_001100170, NM_001400086, NM_001400087, NM_001400088, NM_001400089, NM_001400090, NM_001400091, NM_001400100, NM_001400101, NM_001400102, NM_001400103, NM_001400104, NM_001400105, NM_001400106, NM_001400107, NM_001400108, NM_001400109, NM_001400110, NM_001400111, NM_001400112, NM_001400113, NM_001400114, NM_001400115, NM_001400116, NM_001400117, NM_001400118, NM_001400119, NM_001400120, NM_001400121, NM_001400122, NM_001400123, NM_001400124, NM_001400125, NM_001400126, NM_001400127, NM_001400128, NM_001400129, NM_001400130, NM_001400131, NM_001400132, NM_001400133, NM_001400134, NM_001400135, NM_001400137, NM_001400138, NM_001400140, NM_001400142, NM_001400143, NM_001400144, NM_001400145, NM_006839

CCDS: CCDS46355, CCDS46356, CCDS46357, CCDS92794

Canonical transcript exons

ENST00000410111 — 15 exons

Exon	Start	End
ENSE00000768002	86158592	86158721
ENSE00001579120	86151297	86151520
ENSE00001579210	86195338	86195462
ENSE00001603077	86143936	86144881
ENSE00001678065	86146068	86146197
ENSE00001730137	86147702	86147833
ENSE00002515793	86153560	86153574
ENSE00003502701	86171208	86171345
ENSE00003510496	86159536	86159671
ENSE00003514779	86179433	86179622
ENSE00003602665	86173650	86173761
ENSE00003609200	86166508	86166644
ENSE00003610406	86170749	86170844
ENSE00003620029	86161976	86162079
ENSE00003691137	86181299	86181372

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 97.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 79.5383 / max 286.2854, expressed in 1826 samples.

Highest expression (Bgee): heart left ventricle, cardiac ventricle, adrenal tissue, gastrocnemius, apex of heart.

Genetic regulation across tissues (GTEx eQTL / sQTL)

IMMT is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 45 tissues and its splicing (sQTL) in 11 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 56 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Not Sun Exposed Suprapubic	eqtl	1.0e-78	-0.50	2:86172969:G:T
Skin Sun Exposed Lower leg	eqtl	3.6e-76	-0.45	2:86187730:G:C
Artery Tibial	eqtl	5.4e-70	-0.38	2:86195693:T:G
Testis	eqtl	8.6e-67	-0.78	2:86152990:G:A
Whole Blood	eqtl	2.1e-61	-0.28	2:86171083:C:T
Nerve Tibial	eqtl	3.1e-49	-0.33	2:86178284:T:C
Esophagus Mucosa	eqtl	2.2e-47	-0.32	2:86187730:G:C
Cells EBV-transformed lymphocytes	eqtl	1.4e-45	-0.50	2:86150426:A:G
Esophagus Muscularis	eqtl	1.8e-45	-0.36	2:86172969:G:T
Esophagus Gastroesophageal Junction	eqtl	4.0e-39	-0.31	2:86172969:G:T
Pancreas	eqtl	3.9e-38	-0.57	2:86156048:C:A
Artery Aorta	eqtl	2.6e-37	-0.41	2:86178284:T:C
Adipose Subcutaneous	eqtl	5.0e-36	-0.29	2:86172969:G:T
Cells Cultured fibroblasts	eqtl	8.7e-35	-0.17	2:86187730:G:C
Colon Sigmoid	eqtl	8.0e-32	-0.36	2:86151169:T:C
Lung	eqtl	1.7e-29	-0.24	2:86168838:T:C
Colon Transverse	eqtl	4.6e-29	-0.22	2:86156048:C:A
Stomach	eqtl	4.1e-24	-0.20	2:86178284:T:C
Thyroid	eqtl	3.3e-23	-0.22	2:86156048:C:A
Brain Nucleus accumbens basal ganglia	eqtl	1.6e-18	-0.34	2:86150426:A:G

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
29526	77.7681	1826
29527	1.5862	1017
29525	0.1840	77

Top tissues by expression

showing 100 of 301 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
heart left ventricle	UBERON:0002084	97.94	gold quality
cardiac ventricle	UBERON:0002082	97.92	gold quality
adrenal tissue	UBERON:0018303	97.89	gold quality
gastrocnemius	UBERON:0001388	97.80	gold quality
apex of heart	UBERON:0002098	97.63	gold quality
right atrium auricular region	UBERON:0006631	97.60	gold quality
biceps brachii	UBERON:0001507	97.55	gold quality
muscle of leg	UBERON:0001383	97.52	gold quality
cardiac atrium	UBERON:0002081	97.44	gold quality
heart right ventricle	UBERON:0002080	97.38	gold quality
heart	UBERON:0000948	97.30	gold quality
muscle organ	UBERON:0001630	97.22	gold quality
skeletal muscle organ	UBERON:0014892	97.22	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.11	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.08	gold quality
right adrenal gland cortex	UBERON:0035827	97.06	gold quality
right adrenal gland	UBERON:0001233	97.02	gold quality
body of tongue	UBERON:0011876	96.96	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.79	gold quality
deltoid	UBERON:0001476	96.77	gold quality
left ventricle myocardium	UBERON:0006566	96.77	gold quality
triceps brachii	UBERON:0001509	96.72	gold quality
left adrenal gland	UBERON:0001234	96.65	gold quality
skeletal muscle tissue	UBERON:0001134	96.63	gold quality
adrenal gland	UBERON:0002369	96.46	gold quality
left adrenal gland cortex	UBERON:0035825	96.40	gold quality
adrenal cortex	UBERON:0001235	96.39	gold quality
gluteal muscle	UBERON:0002000	96.38	gold quality
renal medulla	UBERON:0000362	96.32	gold quality
myocardium	UBERON:0002349	96.30	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.28	gold quality
colonic mucosa	UBERON:0000317	96.27	gold quality
rectum	UBERON:0001052	96.27	gold quality
muscle tissue	UBERON:0002385	96.25	gold quality
mucosa of transverse colon	UBERON:0004991	96.20	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.13	gold quality
vastus lateralis	UBERON:0001379	96.12	gold quality
quadriceps femoris	UBERON:0001377	96.10	gold quality
secondary oocyte	CL:0000655	95.93	gold quality
substantia nigra pars compacta	UBERON:0001965	95.76	gold quality
tibialis anterior	UBERON:0001385	95.64	gold quality
transverse colon	UBERON:0001157	95.56	gold quality
jejunum	UBERON:0002115	95.51	gold quality
duodenum	UBERON:0002114	95.27	gold quality
jejunal mucosa	UBERON:0000399	95.26	gold quality
adult mammalian kidney	UBERON:0000082	95.25	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.18	gold quality
ventricular zone	UBERON:0003053	95.06	gold quality
tongue	UBERON:0001723	95.01	gold quality
large intestine	UBERON:0000059	94.99	gold quality
islet of Langerhans	UBERON:0000006	94.98	gold quality
colon	UBERON:0001155	94.98	gold quality
ganglionic eminence	UBERON:0004023	94.93	gold quality
lateral globus pallidus	UBERON:0002476	94.90	gold quality
embryo	UBERON:0000922	94.83	gold quality
body of stomach	UBERON:0001161	94.82	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.80	gold quality
sigmoid colon	UBERON:0001159	94.79	gold quality
lower esophagus	UBERON:0013473	94.79	gold quality
intestine	UBERON:0000160	94.78	gold quality
metanephros cortex	UBERON:0010533	94.72	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.60	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.54	gold quality
left testis	UBERON:0004533	94.54	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.51	gold quality
right testis	UBERON:0004534	94.46	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.31	gold quality
body of pancreas	UBERON:0001150	94.29	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.29	gold quality
stomach	UBERON:0000945	94.22	gold quality
kidney	UBERON:0002113	94.18	gold quality
small intestine	UBERON:0002108	94.17	gold quality
cortical plate	UBERON:0005343	94.13	gold quality
pancreas	UBERON:0001264	94.04	gold quality
oral cavity	UBERON:0000167	93.96	gold quality
pons	UBERON:0000988	93.95	gold quality
testis	UBERON:0000473	93.94	gold quality
popliteal artery	UBERON:0002250	93.88	gold quality
vena cava	UBERON:0004087	93.88	gold quality
tibial artery	UBERON:0007610	93.88	gold quality
esophagus	UBERON:0001043	93.84	gold quality
fundus of stomach	UBERON:0001160	93.80	gold quality
dorsal root ganglion	UBERON:0000044	93.77	gold quality
right frontal lobe	UBERON:0002810	93.75	gold quality
mucosa of stomach	UBERON:0001199	93.74	gold quality
stromal cell of endometrium	CL:0002255	93.71	gold quality
smooth muscle tissue	UBERON:0001135	93.68	gold quality
prefrontal cortex	UBERON:0000451	93.67	gold quality
lymph node	UBERON:0000029	93.64	gold quality
middle temporal gyrus	UBERON:0002771	93.64	gold quality
aorta	UBERON:0000947	93.57	gold quality
left coronary artery	UBERON:0001626	93.57	gold quality
pharyngeal mucosa	UBERON:0000355	93.56	gold quality
superior surface of tongue	UBERON:0007371	93.53	gold quality
descending thoracic aorta	UBERON:0002345	93.47	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.44	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.43	gold quality
coronary artery	UBERON:0001621	93.42	gold quality
oocyte	CL:0000023	93.33	gold quality
diaphragm	UBERON:0001103	93.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Tongue	tissue	270.0
Skeletal muscle	tissue	186.6	low
Heart muscle	tissue	148.3	high
Frontal cortex	tissue	107.2
Caudate putamen	tissue	99.7
Parathyroid gland	tissue	84.7	high
Cerebral cortex	tissue	78.9	low
Somatosensory cortex	tissue	78.9
Kidney	tissue	75.5	high
Pons	tissue	73.6
Superior colliculi	tissue	72.1
Occipital cortex	tissue	71.7
Thalamus	tissue	71.3
Motor cortex	tissue	70.6
Prefrontal cortex	tissue	70.4
Midbrain	tissue	67.3
Retrosplenial and cingulate cortex	tissue	66.5
Substantia nigra	tissue	65.6
Choroid plexus	tissue	65.5
Hippocampal formation	tissue	64.3
Entorhinal cortex	tissue	64.3
Cerebellum	tissue	63.7	medium
Temporal cortex	tissue	63.6
Retrosplenial cortex	tissue	62.5
Spinal cord	tissue	61.4
Medulla oblongata	tissue	61.2
Adrenal gland	tissue	60.4	medium
Olfactory bulb	tissue	59.2
Putamen	tissue	58.1
Ventral forebrain	tissue	57.9
Insular cortex	tissue	55.6
Liver	tissue	55.3	low
Septum	tissue	55.3
Hypothalamus	tissue	54.9
Rectum	tissue	54.6	medium
Duodenum	tissue	54.0	medium
Colon	tissue	53.4	medium
Periaqueductal gray	tissue	53.0
Basal ganglia	tissue	51.6	low
Locus coeruleus	tissue	51.3
Amygdala	tissue	51.0
Postcentral gyrus	tissue	50.3
Thymus	tissue	48.7
Tonsil	tissue	44.2	medium
Small intestine	tissue	43.9	medium
Corpus callosum	tissue	43.7
Lymph node	tissue	41.4	medium
Stomach 1	tissue	41.4	high
Testis	tissue	40.8	medium
Retina	tissue	39.3
Nucleus accumbens	tissue	39.3
Bone marrow	tissue	38.1	not detected
Urinary bladder	tissue	37.7	medium
Hippocampus	tissue	37.3	medium
Adipose tissue	tissue	37.1	not detected
Smooth muscle	tissue	36.3	low
Esophagus	tissue	35.7	low
Salivary gland	tissue	35.7	low
Placenta	tissue	34.5	low
Pancreas	tissue	34.0	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Ventral spinal cord (61.4), Dorsal hippocampus (61.0), Subiculum (59.7), Ventral hippocampus (59.6), Dorsal spinal cord (54.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

showing 30 of 36 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-4684-3P	98.24	69.91	1075
HSA-MIR-506-5P	98.02	67.41	1065

Functional genomics

gnomAD constraint: pLI 0.000396, LOEUF 0.668, missense Z 0.81 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000410111 — one region, missense o/e 0.91.

Literature-anchored findings (GeneRIF, showing 23)

• Data show that the nuclear matrix protein matrin 3, cytoskeletal motor protein HMP, and the circadian clock protein lark were significantly decreased in fetal Down syndrome brain. (PMID:12469345)
• mitofilin is a critical organizer of the mitochondrial cristae morphology and thus indispensable for normal mitochondrial function (PMID:15647377)
• role in protein import related to maintenance of mitochondrial structure is suggested; mitofilin helps regulate mitochondrial morphology and four of the associated proteins (metaxins 1 and 2, SAM50 and CHCHD3) have been implicated in protein import (PMID:17624330)
• The mitochondrial dysfunction induced by DISC1 deficiency was partially reversed by coexpression of Mitofilin, confirming a functional link between DISC1 and Mitofilin for the normal mitochondrial function. (PMID:20880836)
• CHCM1/CHCHD6, novel mitochondrial protein linked to regulation of mitofilin and mitochondrial cristae morphology. (PMID:22228767)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• mitofilin distinctly functions in mitochondrial cristae remodeling and controls cytochrome c release during apoptosis. (PMID:23058921)
• APOOL is a cardiolipin-binding component of the Mitofilin/MINOS protein complex. (PMID:23704930)
• Mitofilin, a mitochondria protein, is shown to be related to cardiac hypertrophy for the first time, which enhances our understanding of the role of mitochondria in cardiac hypertrophy. (PMID:24555791)
• Transgenic overexpression of mitofilin preserves mitochondrial structure, leading to restoration of mitochondrial function and attenuation of cardiac contractile dysfunction in the diabetic heart. (PMID:25463274)
• Mic60 interacted with mtDNA and was involved in the architecture of mtDNA D-loop region. Taken together, our findings reveal a previously unrecognized important role of Mic60 in mtDNA transcription. (PMID:25612828)
• Mitofilin-knockdown cells showed decreased mitochondrial membrane potential (DeltaPsim) and intracellular ATP content, which were minimally affected in CHCHD6-knockout cells. (PMID:26530328)
• PKA-mediated phosphorylation of MIC60 negatively regulates mitochondrial clearance that is initiated by PINK1 and Parkin. (PMID:27153535)
• Sub-mitochondrial localization of the genetic-tagged mitochondrial intermembrane space-bridging components Mic19, Mic60 and Sam50. (PMID:28808085)
• It analyses revealed that Trak1 interacts and colocalizes with mitofusins on the outer mitochondrial membrane and functions with mitofusins to promote mitochondrial tethering and fusion. (PMID:28924745)
• Mitofilin, apoptosis-inducing factor (AIF) and poly(ADP-ribose) polymerase (PARP) expression were measured by Western blot analysis. (PMID:29489384)
• Pediatric ependymoma: GNAO1, ASAH1, IMMT and IPO7 protein expression and 5-year prognosis correlation. (PMID:31505435)
• Study demonstrated that high-IMMT expression is related to some clinicopathological parameters of patients with lung adenocarcinoma, and that its expression is an independent prognostic predictor of poorer survival. (PMID:31583841)
• CHCHD10-regulated OPA1-mitofilin complex mediates TDP-43-induced mitochondrial phenotypes associated with frontotemporal dementia. (PMID:32369233)
• Multicolor 3D MINFLUX nanoscopy of mitochondrial MICOS proteins. (PMID:32788360)
• Conserved GxxxG and WN motifs of MIC13 are essential for bridging two MICOS subcomplexes. (PMID:34271005)
• Mitochondrial developmental encephalopathy with bilateral optic neuropathy related to homozygous variants in IMMT gene. (PMID:34842280)
• Suppressing mitochondrial inner membrane protein (IMMT) inhibits the proliferation of breast cancer cells through mitochondrial remodeling and metabolic regulation. (PMID:38834715)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	immt	ENSDARG00000102874
mus_musculus	Immt	ENSMUSG00000052337
rattus_norvegicus	Immt	ENSRNOG00000009097
drosophila_melanogaster	Mitofilin	FBGN0019960
caenorhabditis_elegans		WBGENE00012315
caenorhabditis_elegans		WBGENE00020511

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1923864) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 37 distinct phenotype terms.

Mouse phenotype (MP)	Records
small cerebellum	1
decreased Purkinje cell number	1
impaired coordination	1
abnormal gait	1
short stride length	1
decreased embryo size	1
abnormal motor capabilities/coordination/movement	1
increased cellular sensitivity to X-ray irradiation induced cell death	1
increased neuron apoptosis	1
neurofibrillary tangles	1
oxidative stress	1
increased cellular glucose import	1
increased oxygen consumption	1
decreased oxygen consumption	1
increased circulating glucose level	1
abnormal mitochondrial physiology	1
enlarged lateral ventricles	1
increased carbon dioxide production	1
decreased carbon dioxide production	1
increased circulating creatine kinase level	1
increased respiratory quotient	1
decreased respiratory quotient	1
abnormal mitochondrial ATP synthesis coupled electron transport	1
abnormal oxidative phosphorylation	1
embryonic lethality during organogenesis, complete penetrance	1

+12 more (showing top 25).

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
POLR1A	protein-coding	25885
MRPL35	protein-coding	51318
PTCD3	protein-coding	55037
REEP1	protein-coding	65055
SNORD94	snoRNA	692225
MIR4779	ncRNA	100616159
KDM3A	protein-coding	55818

Protein

Protein identifiers

MICOS complex subunit MIC60 — Q16891 (reviewed: Q16891)

Alternative names: Cell proliferation-inducing gene 4/52 protein, Mitochondrial inner membrane protein, Mitofilin, p87/89

All UniProt accessions (5): B9A067, C9J406, D6RAW4, Q16891, H7C463

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. Plays an important role in the maintenance of the MICOS complex stability and the mitochondrial cristae morphology.

Subunit / interactions. Component of the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and MICOS13/MIC13. This complex was also known under the names MINOS or MitOS complex. 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. Interacts with HSPA1A/HSPA1B and OPA1, preferentially with the soluble OPA1 form. Interacts with MICOS13/MIC13, MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, SAMM50 and TMEM11. Interacts with APOO/MIC23/MIC26 and APOOL/MIC27. Interacts with ARMC1. Interacts with ARMC12. Interacts with mitochondrial microprotein SHMOOSE. (Microbial infection) Interacts with human cytomegalovirus protein UL13; this interaction alters cristae architecture.

Subcellular location. Mitochondrion inner membrane. Mitochondrion.

Similarity. Belongs to the MICOS complex subunit Mic60 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q16891-1	1	yes
Q16891-2	2
Q16891-3	3
Q16891-4	4

RefSeq proteins (52): NP_001093639, NP_001093640, NP_001387015, NP_001387016, NP_001387017, NP_001387018, NP_001387019, NP_001387020, NP_001387029, NP_001387030, NP_001387031, NP_001387032, NP_001387033, NP_001387034, NP_001387035, NP_001387036, NP_001387037, NP_001387038, NP_001387039, NP_001387040, NP_001387041, NP_001387042, NP_001387043, NP_001387044, NP_001387045, NP_001387046, NP_001387047, NP_001387048, NP_001387049, NP_001387050, NP_001387051, NP_001387052, NP_001387053, NP_001387054, NP_001387055, NP_001387056, NP_001387057, NP_001387058, NP_001387059, NP_001387060, NP_001387061, NP_001387062, NP_001387063, NP_001387064, NP_001387066, NP_001387067, NP_001387069, NP_001387071, NP_001387072, NP_001387073, NP_001387074, NP_006830* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019133	MIC60	Family

Pfam: PF09731

UniProt features (33 total): sequence conflict 11, modified residue 9, splice variant 3, topological domain 2, sequence variant 2, region of interest 2, transit peptide 1, chain 1, transmembrane region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
9QWR	MIC60 helical bundle dimer	X-RAY DIFFRACTION	2.78

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16891-F1	74.81	0.32

Human Protein Atlas

Protein class: Transporters, Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria

Antibody reliability (HPA): IH supported · IF enhanced

Functional residue map

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

Post-translational modifications (9)

Type	Positions
Phosphoserine	113, 223, 388, 390, 103, 112
N6-acetyllysine	211, 222, 451

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: 245 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, MORF_DNMT1, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCGCANK_UNKNOWN, MORF_BUB1, LFA1_Q6, MORF_RRM1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, DITTMER_PTHLH_TARGETS_UP, AACYNNNNTTCCS_UNKNOWN, TGACCTY_ERR1_Q2, MORF_HDAC2, GOBP_CRISTAE_FORMATION, ATGTTAA_MIR302C

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

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (9): SAM complex (GO:0001401), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), membrane (GO:0016020), mitochondrial crista junction (GO:0044284), MICOS complex (GO:0061617), MIB complex (GO:0140275), mitochondrial envelope (GO:0005740)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Mitochondrial biogenesis	1
Organelle biogenesis and maintenance	1

GO top-level categories

17 GO namespaces:

Category	Terms
inner mitochondrial membrane protein complex	2
mitochondrial membrane organization	1
inner mitochondrial membrane organization	1
nucleic acid binding	1
binding	1
mitochondrial outer membrane translocase complex	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial envelope	1
organelle envelope lumen	1
cellular anatomical structure	1
mitochondrial inner membrane	1
organelle membrane contact site	1
mitochondrion	1
organelle envelope	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 13 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 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
membrane	CC	high-throughput assay
mitochondrial inner membrane	CC	direct assay
mitochondrion	CC	direct assay
RNA binding	MF	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 2,674 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IMMT	CHCHD3	Q9NX63	935
IMMT	SAMM50	Q9Y512	923
IMMT	OXA1L	Q15070	836
IMMT	MPV17	P39210	824
IMMT	COQ7	Q99807	797
IMMT	APOOL	Q6UXV4	787
IMMT	COX18	Q8N8Q8	783
IMMT	PET100	P0DJ07	769
IMMT	APOO	Q9BUR5	763
IMMT	SLC25A16	P16260	758
IMMT	CLK3	P49761	755
IMMT	CHCHD6	Q9BRQ6	751
IMMT	COX11	Q9Y6N1	748
IMMT	TRIM13	O60858	737
IMMT	ERCC3	P19447	720

IntAct

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

showing 30 of 78 partners by confidence:

Partner	Interaction type	MIscore	Records
MTX2	association	0.730	1
HTT	physical association	0.670	6
CHCHD10	association	0.600	4
PDE4DIP	physical association	0.570	2
CHD3	physical association	0.550	2
MRPL44	physical association	0.550	2
PFDN1	physical association	0.550	2
KDM1A	physical association	0.510	2
PDHA1	physical association	0.500	1
ATXN3	physical association	0.460	4
HTRA2	cleavage reaction	0.440	1
FAM107A	physical association	0.400	1
GBP5	physical association	0.400	1
MAP4	physical association	0.400	1
MED13L	physical association	0.400	1
NOL8	physical association	0.400	1
PPID	physical association	0.400	1
SF3A2	physical association	0.400	1
SKIC3	physical association	0.400	1
UBTFL6	physical association	0.400	1
ZFP1	physical association	0.400	1
ALB	physical association	0.370	1
ATXN1	physical association	0.370	1
C8orf33	physical association	0.370	1
CDC37	physical association	0.370	1
CEP126	physical association	0.370	1
CVC2	physical association	0.370	1
EEF1A1	physical association	0.370	1
EP300	physical association	0.370	1
FEZ1	physical association	0.370	1

BioGRID (687 interactions; top human partners by supporting records in a sample of 600 records): CHCHD3 (Affinity Capture-Western; 9 records), SAMM50 (Affinity Capture-Western; 6 records), MARCH5 (Proximity Label-MS; 5 records), MTX2 (Co-fractionation; 5 records), SLC25A46 (Co-fractionation; 4 records), AIFM1 (Affinity Capture-MS; 3 records), BOD1L1 (Cross-Linking-MS (XL-MS); 3 records), CD244 (Affinity Capture-MS; 3 records), DST (Cross-Linking-MS (XL-MS); 3 records), HTRA2 (Proximity Label-MS; 3 records), NCAPD2 (Cross-Linking-MS (XL-MS); 3 records), OCIAD1 (Affinity Capture-MS; 3 records), PDE2A (Affinity Capture-Western; 3 records), PINK1 (Affinity Capture-MS; 3 records), TOMM22 (Proximity Label-MS; 3 records)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
IMMT	“up-regulates activity”	PINK1	binding
PRKACA	“down-regulates activity”	IMMT	phosphorylation

Protein complexes (CORUM) (5)

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

5 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
Mitofilin complex, mitochondrial	7	CHCHD6, DNAJC11, IMMT, MTX1, MTX2, SAMM50, CHCHD3
MICOS subcomplex (CHCHD3, IMMT, MICOS10), mitochondrial	3	IMMT, MICOS10, CHCHD3
MICOS subcomplex (APOO, IMMT), mitochondrial	2	APOO, IMMT

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 78 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.

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrion organization	6	12.8×	4e-03
positive regulation of neuron projection development	6	11.6×	4e-03

Disease & clinical

Genetic variants

Variant evidence for IMMT: 132 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	11
Benign	5

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 24 predictions of 1,059):

Position(s)	Effect	Δscore	Sites
2:86144882–86144883	acceptor_loss	1.0000	5
2:86146056	donor_gain	1.0000
2:86146066–86146067	donor_loss	1.0000	4
2:86146198–86146199	acceptor_loss	1.0000	3
2:86146203	acceptor_gain	1.0000
2:86146210	acceptor_gain	1.0000
2:86147269	acceptor_gain	1.0000
2:86147700–86147701	donor_loss	1.0000	5
2:86147834–86147835	acceptor_loss	1.0000	2
2:86147836	acceptor_gain	1.0000

AlphaMissense

1,060 missense substitutions predicted likely pathogenic (of 4,910 scored), across 374 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
H493	8	0.932	0.991
H490	8	0.894	0.993
F369	8	0.892	0.988
D492	8	0.872	0.950
F71	8	0.834	0.964
D496	8	0.785	0.915
W724	7	0.989	0.999
F635	7	0.971	0.993
W274	7	0.968	0.994
W570	7	0.928	0.987
F535	7	0.921	0.978
H407	7	0.912	0.984
E733	7	0.911	0.984
H409	7	0.884	0.988
E372	7	0.864	0.919
F608	7	0.848	0.965
E716	7	0.846	0.945
H252	7	0.835	0.948
F688	7	0.813	0.951
E476	7	0.792	0.932

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	unfavorable	1.1e-06
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	2e-06
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000139

Disease associations

OMIM: gene MIM:600378 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST004730_1	Facial emotion recognition (sad faces)	2e-6
GCST003542_62	Night sleep phenotypes	5e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0008329	facial emotion recognition measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105768 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 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

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.13	Kd	7.429	nM	CHEMBL5653589
8.13	ED50	7.429	nM	CHEMBL5653589
5.24	Kd	5746	nM	CHEMBL3752910
5.24	ED50	5746	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 6 total; 2 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	2148586: Binding affinity to human IMMT incubated for 45 mins by Kinobead based pull down assay	kd	0.0074	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148586: Binding affinity to human IMMT incubated for 45 mins by Kinobead based pull down assay	kd	5.7461	uM

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression, affects cotreatment, decreases expression	2
bisphenol A	decreases expression, increases expression	2
sodium arsenite	affects cotreatment, increases expression, decreases expression	2
Air Pollutants	increases abundance, decreases expression, affects expression	2
Quercetin	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
beauvericin	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
trichostatin A	increases expression	1
cadmium sulfate	decreases expression	1
microcystin RR	decreases expression, increases expression	1
di-n-butylphosphoric acid	affects expression	1
enniatins	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Irinotecan	affects expression	1
Acetaminophen	increases expression	1
Atrazine	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4012554	Binding	Binding affinity to MICOS complex subunit MIC60 in human INA-6 cells after 3 hrs by nanoLC-MS/MS method	Ugi Reaction-Derived α-Acyl Aminocarboxamides Bind to Phosphatidylinositol 3-Kinase-Related Kinases, Inhibit HSF1-Dependent Heat Shock Response, and Induce Apoptosis in Multiple Myeloma Cells. — *J Med Chem*

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SS54	HAP1 IMMT (-) 1	Cancer cell line	Male
CVCL_SS55	HAP1 IMMT (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

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