MTFR2

Summary

MTFR2 (mitochondrial fission regulator 2, HGNC:21115) is a protein-coding gene on chromosome 6q23.3, encoding Mitochondrial fission regulator 2 (Q6P444). May play a role in mitochondrial aerobic respiration essentially in the testis.

Predicted to be involved in aerobic respiration and mitochondrial fission. Located in mitochondrion.

Source: NCBI Gene 113115 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 72 total
• MANE Select transcript: NM_001099286

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21115
Approved symbol	MTFR2
Name	mitochondrial fission regulator 2
Location	6q23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000146410
Ensembl biotype	protein_coding
Entrez	113115

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000367784, ENST00000418509, ENST00000420702, ENST00000445767, ENST00000451457, ENST00000527338, ENST00000532958, ENST00000919551, ENST00000952723

RefSeq mRNA: 3 — MANE Select: NM_001099286 NM_001099286, NM_001318738, NM_138419

CCDS: CCDS5176

Canonical transcript exons

ENST00000420702 — 8 exons

Exon	Start	End
ENSE00001629537	136249976	136250311
ENSE00003515364	136241444	136241676
ENSE00003559383	136231034	136231388
ENSE00003565761	136244765	136244869
ENSE00003573198	136233325	136233499
ENSE00003592532	136249037	136249153
ENSE00003636140	136242861	136242973
ENSE00003642674	136239466	136239820

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 94.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.9445 / max 88.6392, expressed in 968 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75742	2.9445	968

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	94.87	gold quality
secondary oocyte	CL:0000655	92.50	gold quality
oocyte	CL:0000023	91.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.44	gold quality
sperm	CL:0000019	86.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.04	gold quality
ventricular zone	UBERON:0003053	79.22	gold quality
ileal mucosa	UBERON:0000331	77.24	gold quality
right testis	UBERON:0004534	76.16	gold quality
testis	UBERON:0000473	76.00	gold quality
bone marrow	UBERON:0002371	75.96	gold quality
left testis	UBERON:0004533	75.48	gold quality
mucosa of transverse colon	UBERON:0004991	75.11	gold quality
rectum	UBERON:0001052	73.43	gold quality
trabecular bone tissue	UBERON:0002483	73.21	gold quality
ganglionic eminence	UBERON:0004023	73.12	gold quality
vermiform appendix	UBERON:0001154	72.81	gold quality
stromal cell of endometrium	CL:0002255	71.62	gold quality
tibialis anterior	UBERON:0001385	70.46	gold quality
lymph node	UBERON:0000029	70.18	gold quality
gingival epithelium	UBERON:0001949	70.18	gold quality
esophagus mucosa	UBERON:0002469	68.96	gold quality
epithelium of nasopharynx	UBERON:0001951	68.93	gold quality
lower esophagus mucosa	UBERON:0035834	68.19	gold quality
amniotic fluid	UBERON:0000173	67.89	gold quality
thymus	UBERON:0002370	67.66	gold quality
granulocyte	CL:0000094	67.37	gold quality
palpebral conjunctiva	UBERON:0001812	67.10	gold quality
pancreatic ductal cell	CL:0002079	66.95	silver quality
adult organism	UBERON:0007023	66.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.49

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
TP53	Unknown

miRNA regulators (miRDB)

22 targeting MTFR2, 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-3185	99.99	68.12	1959
HSA-MIR-4496	99.88	68.89	2236
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-6796-3P	98.68	65.49	689
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-924	97.78	66.21	681
HSA-MIR-376C-3P	97.63	68.88	1263
HSA-MIR-592	96.59	67.59	817
HSA-MIR-6806-5P	96.37	68.74	587
HSA-MIR-217-3P	95.67	68.42	1000

Literature-anchored findings (GeneRIF, showing 6)

• Mitochondrial fission regulator 2 (MTFR2) promotes growth, migration, invasion and tumour progression in breast cancer cells. (PMID:31740625)
• Evaluation of clinical value and potential mechanism of MTFR2 in lung adenocarcinoma via bioinformatics. (PMID:34039308)
• Upregulated expression of MTFR2 as a novel biomarker predicts poor prognosis in hepatocellular carcinoma by bioinformatics analysis. (PMID:34156259)
• Transcription factor HOXC10 activates the expression of MTFR2 to regulate the proliferation, invasion and migration of colorectal cancer cells. (PMID:34523692)
• Dysregulation of MTFR2, ATP5IF1 and BAK1 in Sertoli cells relates to idiopathic non-obstructive azoospermia via inhibiting mitochondrial fission and inducing mitochondrial dysfunctiondagger. (PMID:37903059)
• MTFR2-dependent mitochondrial fission promotes HCC progression. (PMID:38238834)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mtfr2	ENSDARG00000060394
mus_musculus	Mtfr2	ENSMUSG00000019992
rattus_norvegicus		ENSRNOG00000078862

Paralogs (2): MTFR1 (ENSG00000066855), MTFR1L (ENSG00000117640)

Protein

Protein identifiers

Mitochondrial fission regulator 2 — Q6P444 (reviewed: Q6P444)

Alternative names: DUF729 domain-containing protein 1

All UniProt accessions (3): Q6P444, E9PN39, H0YEA6

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in mitochondrial aerobic respiration essentially in the testis. Can also promote mitochondrial fission.

Subcellular location. Mitochondrion.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the MTFR1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6P444-1	1	yes
Q6P444-2	2

RefSeq proteins (3): NP_001092756, NP_001305667, NP_612428 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007972	Mtfr1	Family

Pfam: PF05308

UniProt features (13 total): modified residue 4, compositionally biased region 3, splice variant 2, region of interest 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P444-F1	62.11	0.11

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 (4): 328, 2, 119, 291

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 158 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_ORGANELLE_FISSION, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_DN, FOSTER_TOLERANT_MACROPHAGE_UP, GOBP_MITOCHONDRIAL_FISSION, DODD_NASOPHARYNGEAL_CARCINOMA_UP, FISCHER_DREAM_TARGETS, TURASHVILI_BREAST_CARCINOMA_DUCTAL_VS_LOBULAR_UP, GOBP_CELLULAR_RESPIRATION, NUYTTEN_EZH2_TARGETS_DN, MARSON_BOUND_BY_E2F4_UNSTIMULATED

GO Biological Process (3): mitochondrial fission (GO:0000266), mitochondrion organization (GO:0007005), aerobic respiration (GO:0009060)

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

GO Cellular Component (1): mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion organization	1
organelle fission	1
organelle organization	1
cellular respiration	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1166 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTFR2	DERL1	Q9BUN8	431
MTFR2	KRTAP19-7	Q3SYF9	431
MTFR2	C4orf46	Q504U0	374
MTFR2	OR6X1	Q8NH79	370
MTFR2	OR13J1	Q8NGT2	366
MTFR2	ZNF565	Q8N9K5	359
MTFR2	SHCBP1	Q8NEM2	348
MTFR2	TTK	P33981	338
MTFR2	FAM181A	Q8N9Y4	305
MTFR2	CENPN	Q96H22	304
MTFR2	ZNF781	Q8N8C0	303
MTFR2	POTEM	A6NI47	303
MTFR2	FAM72B	Q86X60	274
MTFR2	TTC14	Q96N46	271
MTFR2	ZNF791	Q3KP31	269
MTFR2	PHETA1	Q8N4B1	269

IntAct

53 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ALAS1	MTFR2	psi-mi:“MI:0915”(physical association)	0.560
MTFR2	ALAS1	psi-mi:“MI:0915”(physical association)	0.560
MTFR2	TRIM23	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	MTFR2	psi-mi:“MI:0915”(physical association)	0.560
MAGEA12	MTFR2	psi-mi:“MI:0915”(physical association)	0.560
TFIP11	MTFR2	psi-mi:“MI:0915”(physical association)	0.560
TRIM23	MTFR2	psi-mi:“MI:0915”(physical association)	0.560
MTFR2	GOLGA2	psi-mi:“MI:0915”(physical association)	0.560
MTFR2	TFIP11	psi-mi:“MI:0915”(physical association)	0.560
MTFR2	MAGEA12	psi-mi:“MI:0915”(physical association)	0.560
SLC2A12	METTL15	psi-mi:“MI:0914”(association)	0.530
NPY2R	RTL8C	psi-mi:“MI:0914”(association)	0.530
SCNN1D	ABHD16A	psi-mi:“MI:0914”(association)	0.530
ATG14	CETN2	psi-mi:“MI:0914”(association)	0.530
MTFR2	CFTR	psi-mi:“MI:0915”(physical association)	0.520
HTRA2	HAX1	psi-mi:“MI:2364”(proximity)	0.420
MTFR2	SIRT1	psi-mi:“MI:0915”(physical association)	0.400
MTFR2	KLHDC2	psi-mi:“MI:0915”(physical association)	0.400
MTFR2	SPTB	psi-mi:“MI:0915”(physical association)	0.400
PB2	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (66): MTFR2 (Two-hybrid), MTFR2 (Two-hybrid), MTFR2 (Two-hybrid), MTFR2 (Two-hybrid), MTFR2 (Two-hybrid), KLHDC2 (Affinity Capture-MS), MTFR2 (Affinity Capture-MS), MTFR2 (Affinity Capture-MS), MTFR2 (Affinity Capture-MS), MTFR2 (Affinity Capture-MS), MTFR2 (Affinity Capture-MS), SIRT1 (Affinity Capture-MS), MTFR2 (Affinity Capture-MS), MTFR2 (Affinity Capture-MS), MTFR2 (Affinity Capture-MS)

ESM2 similar proteins: A2AIW0, A2YX04, A5WUN7, A8MWX3, B0K035, B2GUZ2, D3IUT5, D4A4D7, F1RCE7, G3V9A7, Q08BD8, Q0VFP3, Q3ZBW7, Q4R707, Q4V7T5, Q52KF3, Q58CR1, Q5R3Z9, Q5T5Y3, Q5XII9, Q640U0, Q641E3, Q6AWX6, Q6DF94, Q6GP48, Q6IRN6, Q6NPP4, Q6P444, Q6S7F2, Q6Z8M8, Q700C2, Q75LH6, Q7T3E8, Q7YR76, Q8BHE0, Q8C263, Q8GSA7, Q8IZQ8, Q8K298, Q8RY95

Diamond homologs: B0K035, F1RCE7, G3V9A7, Q08BD8, Q0VFP3, Q3ZBW7, Q4V7T5, Q58CR1, Q5R3Z9, Q5RFN3, Q5XII9, Q6GP48, Q6P444, Q7T3E8, Q8VED8, Q99MB2, Q9CWE0, Q9H019, Q15390, Q9PTD5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1050 predictions. Top by Δscore:

Variant	Effect	Δscore
6:136231384:CCAAA:C	acceptor_gain	1.0000
6:136231385:CAAA:C	acceptor_gain	1.0000
6:136231385:CAAAC:C	acceptor_gain	1.0000
6:136231388:ACTG:A	acceptor_loss	1.0000
6:136231389:C:CC	acceptor_gain	1.0000
6:136233319:GCTTA:G	donor_loss	1.0000
6:136233320:CTTA:C	donor_loss	1.0000
6:136233322:T:TG	donor_loss	1.0000
6:136233323:A:AC	donor_gain	1.0000
6:136233323:AC:A	donor_gain	1.0000
6:136233324:C:CC	donor_gain	1.0000
6:136233324:C:CT	donor_loss	1.0000
6:136233324:CC:C	donor_gain	1.0000
6:136241440:TTA:T	donor_loss	1.0000
6:136241441:TAC:T	donor_loss	1.0000
6:136241442:A:AC	donor_gain	1.0000
6:136241442:ACTAG:A	donor_loss	1.0000
6:136241443:C:A	donor_loss	1.0000
6:136241443:C:CA	donor_gain	1.0000
6:136241443:CT:C	donor_gain	1.0000
6:136241443:CTA:C	donor_gain	1.0000
6:136241443:CTAG:C	donor_gain	1.0000
6:136241443:CTAGA:C	donor_gain	1.0000
6:136241467:T:A	donor_gain	1.0000
6:136241672:TATTT:T	acceptor_gain	1.0000
6:136241673:ATTT:A	acceptor_gain	1.0000
6:136241674:TTT:T	acceptor_gain	1.0000
6:136241675:TT:T	acceptor_gain	1.0000
6:136241677:C:CC	acceptor_gain	1.0000
6:136241678:T:C	acceptor_loss	1.0000

AlphaMissense

2537 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:136244825:A:C	S36R	0.988
6:136244825:A:T	S36R	0.988
6:136244827:T:G	S36R	0.988
6:136241512:A:G	L149P	0.987
6:136244820:A:T	V38D	0.980
6:136241503:A:G	L152P	0.976
6:136233406:A:C	F321L	0.975
6:136233406:A:T	F321L	0.975
6:136233408:A:G	F321L	0.975
6:136233419:A:T	L317H	0.975
6:136244817:C:G	R39P	0.975
6:136233340:A:C	S343R	0.970
6:136233340:A:T	S343R	0.970
6:136233342:T:G	S343R	0.970
6:136233419:A:G	L317P	0.970
6:136244818:G:T	R39S	0.969
6:136233423:C:G	A316P	0.967
6:136241489:C:G	A157P	0.966
6:136239505:A:G	L277P	0.964
6:136241494:T:G	Q155P	0.963
6:136241524:A:G	L145P	0.958
6:136233431:A:T	I313K	0.957
6:136241500:C:G	R153P	0.952
6:136244777:T:A	R52S	0.950
6:136244777:T:G	R52S	0.950
6:136244808:C:T	G42E	0.946
6:136244826:C:A	S36I	0.943
6:136233431:A:G	I313T	0.942
6:136244828:C:A	R35S	0.942
6:136244828:C:G	R35S	0.942

dbSNP variants (sampled 300 via entrez): RS1000303532 (6:136236006 C>T), RS1000494300 (6:136247485 T>C), RS1000895421 (6:136251735 A>G), RS1001083912 (6:136248045 C>G), RS1001110114 (6:136246069 C>A,T), RS1001536579 (6:136247564 T>C), RS1001545979 (6:136243197 C>A,T), RS1001581877 (6:136246924 A>G), RS1001632248 (6:136240918 CG>C), RS1001717004 (6:136232403 T>C), RS1001819076 (6:136235642 A>C), RS1001834395 (6:136249351 T>C), RS1001884750 (6:136244542 C>T), RS1002057356 (6:136233769 T>C), RS1002469940 (6:136245258 T>A,G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_790	Metabolite levels	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010395	sphingomyelin 22:0 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	3
sodium arsenite	increases expression, decreases expression	2
(+)-JQ1 compound	decreases expression, increases expression	2
Valproic Acid	decreases methylation, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
afuresertib	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
bisphenol A	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	decreases expression	1
teriflunomide	decreases expression	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Dasatinib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Vorinostat	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1

Clinical trials (associated diseases)

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