MTLN

Summary

MTLN (mitoregulin, HGNC:27339) is a protein-coding gene on chromosome 2q13, encoding Mitoregulin (Q8NCU8). Positively regulates mitochondrial complex assembly and/or stability.

Involved in several processes, including positive regulation of mitochondrial membrane potential; positive regulation of sequestering of calcium ion; and triglyceride homeostasis. Located in mitochondrion.

Source: NCBI Gene 205251 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001384134

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27339
Approved symbol	MTLN
Name	mitoregulin
Location	2q13
Locus type	gene with protein product
Status	Approved
Aliases	MOXI, LEMP, MPM, TILR
Ensembl gene	ENSG00000175701
Ensembl biotype	protein_coding
OMIM	620770
Entrez	205251

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000414416, ENST00000426713, ENST00000611969

RefSeq mRNA: 1 — MANE Select: NM_001384134 NM_001384134

CCDS: CCDS92837

Canonical transcript exons

ENST00000611969 — 2 exons

Exon	Start	End
ENSE00001529771	110211529	110211622
ENSE00003739412	110212215	110212547

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 99.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.1833 / max 458.2304, expressed in 1764 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30123	39.6028	1764
30122	2.0211	1159
30121	0.5594	249

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	99.28	gold quality
apex of heart	UBERON:0002098	99.02	gold quality
tibialis anterior	UBERON:0001385	98.86	gold quality
gastrocnemius	UBERON:0001388	98.84	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.75	gold quality
muscle of leg	UBERON:0001383	98.24	gold quality
biceps brachii	UBERON:0001507	97.96	gold quality
skeletal muscle tissue	UBERON:0001134	97.88	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.88	gold quality
heart left ventricle	UBERON:0002084	97.87	gold quality
body of tongue	UBERON:0011876	97.83	gold quality
cardiac ventricle	UBERON:0002082	97.75	gold quality
right atrium auricular region	UBERON:0006631	97.09	gold quality
pancreatic ductal cell	CL:0002079	96.81	gold quality
cardiac atrium	UBERON:0002081	96.73	gold quality
left ventricle myocardium	UBERON:0006566	96.62	gold quality
heart	UBERON:0000948	96.54	gold quality
quadriceps femoris	UBERON:0001377	96.38	gold quality
lower esophagus	UBERON:0013473	96.03	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.03	gold quality
muscle tissue	UBERON:0002385	96.02	gold quality
mucosa of transverse colon	UBERON:0004991	95.98	gold quality
vastus lateralis	UBERON:0001379	95.91	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.73	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.70	gold quality
left coronary artery	UBERON:0001626	95.60	gold quality
deltoid	UBERON:0001476	95.59	gold quality
anterior cingulate cortex	UBERON:0009835	95.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.39	gold quality
tongue	UBERON:0001723	95.23	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.48
E-GEOD-93593	yes	7.95

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• LINC00116 enhances cervical cancer tumorigenesis through miR-106a/c-Jun pathway. (PMID:31693227)
• Mitoregulin Controls beta-Oxidation in Human and Mouse Adipocytes. (PMID:32243843)
• Long non-coding RNA TILR constitutively represses TP53 and apoptosis in lung cancer. (PMID:36522487)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mtln	ENSMUSG00000051319

Protein

Protein identifiers

Mitoregulin — Q8NCU8 (reviewed: Q8NCU8)

Alternative names: Micropeptide in mitochondria, Micropeptide regulator of beta-oxidation, Small integral membrane protein 37, lncRNA-encoded micropeptide

All UniProt accessions (1): Q8NCU8

UniProt curated annotations — full annotation on UniProt →

Function. Positively regulates mitochondrial complex assembly and/or stability. Increases mitochondrial membrane potential while decreasing mitochondrial reactive oxygen species. Increases mitochondrial respiration rate. Increased mitochondrial respiratory activity promotes myogenic differentiation which facilitates muscle growth and regeneration. Increases mitochondrial calcium retention capacity. Plays a role in maintenance of cellular lipid composition through its interaction with cytochrome b5 reductase CYB5R3 which is required for mitochondrial respiratory complex I activity. Interacts with the mitochondrial trifunctional enzyme complex (MTE) and enhances fatty acid beta-oxidation. Not required for MTE formation or stability. Modulates triglyceride clearance in adipocytes through its role in regulating fatty acid beta-oxidation and lipolysis.

Subunit / interactions. Interacts with mitochondrial trifunctional enzyme, a heterotetrameric complex composed of 2 HADHA subunits and 2 HADHB subunits. Interacts with cytochrome b5 reductase CYB5R3; the interaction is required to maintain cellular lipid composition and leads to stimulation of mitochondrial respiratory complex I activity. Interacts with ATP synthase subunit ATP5F1B/ATP5B.

Subcellular location. Mitochondrion inner membrane.

Similarity. Belongs to the mitoregulin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NCU8-2	Short	yes
Q8NCU8-1	Long

RefSeq proteins (1): NP_001371063* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR038778	Mtln	Family

Pfam: PF22002

UniProt features (6 total): topological domain 2, initiator methionine 1, chain 1, transmembrane region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NCU8-F1	90.16	0.72

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 105 (showing top): GOBP_LIPID_MODIFICATION, GOBP_ACYLGLYCEROL_HOMEOSTASIS, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_SEQUESTERING_OF_CALCIUM_ION, TGCACTT_MIR519C_MIR519B_MIR519A, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_KETONE_METABOLIC_PROCESS, GOBP_REGULATION_OF_FATTY_ACID_METABOLIC_PROCESS, GOBP_LIPID_HOMEOSTASIS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (9): lipid metabolic process (GO:0006629), fatty acid beta-oxidation (GO:0006635), positive regulation of mitochondrial membrane potential (GO:0010918), positive regulation of protein-containing complex assembly (GO:0031334), positive regulation of fatty acid beta-oxidation (GO:0032000), cellular respiration (GO:0045333), striated muscle cell differentiation (GO:0051146), obsolete positive regulation of sequestering of calcium ion (GO:0051284), triglyceride homeostasis (GO:0070328)

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

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	1
fatty acid catabolic process	1
fatty acid ligase activity	1
fatty acid oxidation	1
positive regulation of membrane potential	1
regulation of mitochondrial membrane potential	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
fatty acid beta-oxidation	1
regulation of fatty acid beta-oxidation	1
positive regulation of fatty acid oxidation	1
positive regulation of lipid catabolic process	1
energy derivation by oxidation of organic compounds	1
muscle cell differentiation	1
acylglycerol homeostasis	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

124 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTLN	NBDY	A0A0U1RRE5	583
MTLN	C20orf204	A0A1B0GTL2	573
MTLN	STRIT1	P0DN84	545
MTLN	MRLN	P0DMT0	507
MTLN	SPAAR	A0A1B0GVQ0	398
MTLN	CYB5R3	P00387	373
MTLN	UQCC6	Q69YU5	366
MTLN	MPG	P29372	365
MTLN	MYMK	A6NI61	338
MTLN	CYB5RL	Q6IPT4	328
MTLN	NCBP2AS2	Q69YL0	323
MTLN	SMIM22	K7EJ46	308
MTLN	SMIM30	A4D0T7	305
MTLN	CYB5R4	Q7L1T6	304
MTLN	ERLN	P0DI80	300

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A2BPC1, A2BUV0, A2C0G6, A2C9Q5, A2CBR5, A3N0M3, A3PB44, A8G2Y1, B0BPE7, B0CG09, B0JI44, B1X0Z7, B1XN58, B3H1K2, B4EYB8, B7K2V6, B7KHV5, O07516, P40780, P55148, P57047, P57800, P59112, P72752, P73202, P73628, P73930, P74433, P75028, Q0I206, Q10YZ5, Q2JN84, Q2JRR7, Q31CK8, Q31PJ8, Q3MDY0, Q46H47, Q4JUF6, Q5N4M6, Q65VA2

Diamond homologs: Q8BT35, Q8NCU8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1134 predictions. Top by Δscore:

Variant	Effect	Δscore
2:110215676:CCA:C	donor_gain	1.0000
2:110211619:CAAG:C	acceptor_gain	0.9900
2:110212874:ACC:A	acceptor_loss	0.9900
2:110212875:CCTGT:C	acceptor_loss	0.9900
2:110212876:C:CG	acceptor_loss	0.9900
2:110212877:T:A	acceptor_loss	0.9900
2:110214575:ACCTC:A	acceptor_gain	0.9900
2:110215675:A:AC	donor_gain	0.9900
2:110215676:C:CC	donor_gain	0.9900
2:110215676:CCACT:C	donor_gain	0.9900
2:110215807:CCTT:C	acceptor_gain	0.9900
2:110215810:T:C	acceptor_gain	0.9900
2:110215810:T:TC	acceptor_gain	0.9900
2:110215818:A:T	acceptor_gain	0.9900
2:110217652:CACT:C	donor_loss	0.9900
2:110217653:ACTC:A	donor_loss	0.9900
2:110217654:CTCA:C	donor_loss	0.9900
2:110217655:TCACC:T	donor_loss	0.9900
2:110217656:CACCT:C	donor_loss	0.9900
2:110217657:A:C	donor_loss	0.9900
2:110217658:C:CA	donor_loss	0.9900
2:110211623:C:CC	acceptor_gain	0.9800
2:110212876:C:CC	acceptor_gain	0.9800
2:110214576:CCTCT:C	acceptor_gain	0.9800
2:110214577:CTCT:C	acceptor_gain	0.9800
2:110214579:C:G	acceptor_gain	0.9800
2:110215803:TGGGC:T	acceptor_gain	0.9800
2:110215808:C:CC	acceptor_gain	0.9800
2:110215809:T:C	acceptor_gain	0.9800
2:110217651:GCACT:G	donor_loss	0.9800

AlphaMissense

344 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:110212468:C:G	G20R	0.983
2:110212468:C:T	G20R	0.983
2:110212467:C:T	G20E	0.982
2:110212455:C:T	G24D	0.980
2:110212456:C:G	G24R	0.977
2:110212473:G:T	A18D	0.974
2:110212479:G:T	A16D	0.967
2:110212464:A:T	V21E	0.951
2:110212475:G:C	F17L	0.940
2:110212475:G:T	F17L	0.940
2:110212477:A:G	F17L	0.940
2:110212401:A:G	L42P	0.936
2:110212447:C:G	A27P	0.933
2:110212389:A:G	L46P	0.931
2:110212446:G:T	A27E	0.910
2:110212453:A:G	W25R	0.909
2:110212453:A:T	W25R	0.909
2:110212440:C:G	R29P	0.899
2:110212482:A:T	V15E	0.894
2:110212476:A:G	F17S	0.891
2:110212415:C:A	W37C	0.887
2:110212415:C:G	W37C	0.887
2:110212368:A:G	L53P	0.883
2:110212426:A:C	Y34D	0.878
2:110212434:C:G	R31P	0.873
2:110212461:A:T	L22H	0.872
2:110212488:A:T	V13E	0.872
2:110212461:A:C	L22R	0.868
2:110212410:T:A	K39I	0.863
2:110212455:C:A	G24V	0.859

dbSNP variants (sampled 300 via entrez): RS1000114144 (2:110213707 A>G), RS1002176158 (2:110211755 C>T), RS1002213443 (2:110212199 T>A), RS1002220318 (2:110211683 C>T), RS1005731703 (2:110214282 G>A,T), RS1006376355 (2:110211393 A>G), RS1007343820 (2:110212548 G>A,T), RS1007394468 (2:110212221 T>A,C), RS1007415683 (2:110212850 G>A), RS1008346319 (2:110213989 T>A), RS1008421284 (2:110214449 T>C), RS1009718650 (2:110211366 C>T), RS1010044741 (2:110211062 C>T), RS1011454584 (2:110211829 G>A), RS1011873141 (2:110213761 A>G)

Disease associations

OMIM: gene MIM:620770 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	3
sodium arsenite	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
bisphenol A	affects cotreatment, increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
fipronil	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	affects response to substance, decreases expression	1
DEET	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Smoke	increases abundance, decreases expression	1
Thiram	decreases expression	1
Valproic Acid	decreases expression	1

Clinical trials (associated diseases)

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