MTERF3

Summary

MTERF3 (mitochondrial transcription termination factor 3, HGNC:24258) is a protein-coding gene on chromosome 8q22.1, encoding Transcription termination factor 3, mitochondrial (Q96E29). Binds promoter DNA and regulates initiation of transcription. It is a selective cancer dependency (DepMap: 15.3% of cell lines).

Enables transcription cis-regulatory region binding activity. Involved in negative regulation of DNA-templated transcription. Located in cytosol and mitochondrial matrix.

Source: NCBI Gene 51001 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 59 total
• Cancer dependency (DepMap): dependent in 15.3% of screened cell lines
• MANE Select transcript: NM_015942

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24258
Approved symbol	MTERF3
Name	mitochondrial transcription termination factor 3
Location	8q22.1
Locus type	gene with protein product
Status	Approved
Aliases	CGI-12, FLJ10939
Ensembl gene	ENSG00000156469
Ensembl biotype	protein_coding
OMIM	616930
Entrez	51001

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 15 protein_coding, 1 retained_intron

ENST00000287025, ENST00000517720, ENST00000522822, ENST00000523821, ENST00000524341, ENST00000903459, ENST00000903460, ENST00000903461, ENST00000903462, ENST00000903463, ENST00000912663, ENST00000912664, ENST00000912665, ENST00000912666, ENST00000956101, ENST00000956102

RefSeq mRNA: 3 — MANE Select: NM_015942 NM_001286643, NM_001362964, NM_015942

CCDS: CCDS6270, CCDS75772

Canonical transcript exons

ENST00000287025 — 8 exons

Exon	Start	End
ENSE00001026703	96243919	96244080
ENSE00001026704	96246307	96246454
ENSE00001026705	96245860	96245931
ENSE00001026706	96256962	96257114
ENSE00001026707	96258357	96258700
ENSE00001026708	96239402	96239685
ENSE00002128602	96261501	96261610
ENSE00003545938	96250906	96251095

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 99.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.8512 / max 62.7077, expressed in 1763 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94026	9.8512	1763

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.43	gold quality
secondary oocyte	CL:0000655	98.33	gold quality
heart right ventricle	UBERON:0002080	92.43	gold quality
biceps brachii	UBERON:0001507	92.34	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.06	gold quality
cardiac ventricle	UBERON:0002082	89.81	gold quality
heart left ventricle	UBERON:0002084	89.79	gold quality
gastrocnemius	UBERON:0001388	89.58	gold quality
muscle of leg	UBERON:0001383	89.17	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.09	gold quality
muscle organ	UBERON:0001630	88.94	gold quality
germinal epithelium of ovary	UBERON:0001304	88.86	gold quality
vastus lateralis	UBERON:0001379	88.74	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.67	gold quality
heart	UBERON:0000948	88.59	gold quality
parietal pleura	UBERON:0002400	88.42	gold quality
seminal vesicle	UBERON:0000998	88.31	gold quality
left ventricle myocardium	UBERON:0006566	88.17	gold quality
quadriceps femoris	UBERON:0001377	88.16	gold quality
visceral pleura	UBERON:0002401	88.14	gold quality
pleura	UBERON:0000977	88.03	gold quality
skeletal muscle tissue	UBERON:0001134	87.84	gold quality
choroid plexus epithelium	UBERON:0003911	87.82	gold quality
right atrium auricular region	UBERON:0006631	87.81	gold quality
deltoid	UBERON:0001476	87.80	gold quality
endometrium	UBERON:0001295	87.68	gold quality
apex of heart	UBERON:0002098	87.63	gold quality
cardiac atrium	UBERON:0002081	87.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.67

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 15.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• MTERFD1 and MTERFD3 have a role in impairing the completion of mitochondrial DNA replication (PMID:20577816)
• These results demonstrated that MTERFD1 played an oncogenic role in colorectal (CRC) development and enhanced irradiation resistance by regulating IL-6 and IL-11 in CRC cells. MTERFD1 may serve as a potential prognostic and therapeutic marker for radiotherapy in CRC. (PMID:31754344)
• Suppressing MTERF3 inhibits proliferation of human hepatocellular carcinoma via ROS-mediated p38 MAPK activation. (PMID:38177713)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mterf3	ENSDARG00000003207
mus_musculus	Mterf3	ENSMUSG00000021519
rattus_norvegicus	Mterf3	ENSRNOG00000004492
drosophila_melanogaster	mTerf3	FBGN0037008
caenorhabditis_elegans		WBGENE00008236

Protein

Protein identifiers

Transcription termination factor 3, mitochondrial — Q96E29 (reviewed: Q96E29)

Alternative names: Mitochondrial transcription termination factor 3, mTERF domain-containing protein 1, mitochondrial

All UniProt accessions (4): Q96E29, E5RI75, E5RIK9, E5RIY4

UniProt curated annotations — full annotation on UniProt →

Function. Binds promoter DNA and regulates initiation of transcription. Required for normal mitochondrial transcription and translation, and for normal assembly of mitochondrial respiratory complexes. Required for normal mitochondrial function. Maintains 16S rRNA levels and functions in mitochondrial ribosome assembly by regulating the biogenesis of the 39S ribosomal subunit.

Subcellular location. Mitochondrion.

Tissue specificity. Highly expressed in heart, liver, kidney and testis. Detected at lower levels in brain, spleen and lung.

Domain organisation. Contains seven structural repeats of about 35 residues, where each repeat contains three helices. The repeats form a superhelical structure with a solenoid shape.

Similarity. Belongs to the mTERF family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96E29-1	1	yes
Q96E29-2	2
Q96E29-3	3

RefSeq proteins (3): NP_001273572, NP_001349893, NP_057026* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003690	MTERF	Family
IPR038538	MTERF_sf	Homologous_superfamily

Pfam: PF02536

UniProt features (33 total): helix 24, splice variant 2, transit peptide 1, chain 1, region of interest 1, strand 1, compositionally biased region 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3M66	X-RAY DIFFRACTION	1.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96E29-F1	76.28	0.60

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-5205685	PINK1-PRKN Mediated Mitophagy
R-HSA-6793080	rRNA modification in the mitochondrion
R-HSA-9937008	Mitochondrial mRNA modification
R-HSA-1632852	Macroautophagy
R-HSA-5205647	Mitophagy
R-HSA-9612973	Autophagy
R-HSA-9663891	Selective autophagy

MSigDB gene sets: 0 (showing top):

GO Biological Process (5): negative regulation of DNA-templated transcription (GO:0045892), mitochondrial ribosome assembly (GO:0061668), regulation of mitochondrial transcription (GO:1903108), regulation of DNA-templated transcription (GO:0006355), ribosome biogenesis (GO:0042254)

GO Molecular Function (5): transcription cis-regulatory region binding (GO:0000976), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), protein binding (GO:0005515)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), mitochondrial matrix (GO:0005759), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Mitophagy	1
rRNA processing in the mitochondrion	1
Metabolism of RNA	1
Autophagy	1
Selective autophagy	1
Macroautophagy	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
regulation of DNA-templated transcription	2
binding	2
cytoplasm	2
negative regulation of RNA biosynthetic process	1
ribosome assembly	1
mitochondrial transcription	1
regulation of mitochondrial gene expression	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
ribonucleoprotein complex biogenesis	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
nucleic acid binding	1
DNA binding	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
mitochondrion	1
intracellular organelle lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1463 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTERF3	MTERF2	Q49AM1	847
MTERF3	MTERF1	Q99551	840
MTERF3	DDX28	Q9NUL7	777
MTERF3	TFB1M	Q8WVM0	773
MTERF3	NSUN4	Q96CB9	755
MTERF3	MRM3	Q9HC36	752
MTERF3	POLRMT	O00411	743
MTERF3	TFB2M	Q9H5Q4	722
MTERF3	MALSU1	Q96EH3	703
MTERF3	FASTKD2	Q9NYY8	696
MTERF3	ERAL1	O75616	655
MTERF3	TFAM	Q00059	651
MTERF3	TRUB2	O95900	638
MTERF3	PTCD1	O75127	632
MTERF3	MRPL20	Q9BYC9	626

IntAct

216 interactions, top by confidence:

A	B	Type	Score
MED17	MED19	psi-mi:“MI:0914”(association)	0.840
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
FAM120A	SYNCRIP	psi-mi:“MI:0914”(association)	0.640
MTERF3	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.560
AGTRAP	MTERF3	psi-mi:“MI:0915”(physical association)	0.560
MTERF3	FUNDC1	psi-mi:“MI:0915”(physical association)	0.560
CMTM5	MTERF3	psi-mi:“MI:0915”(physical association)	0.560
ARL6IP1	MTERF3	psi-mi:“MI:0915”(physical association)	0.560
MTERF3	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560
MTERF3	CMTM5	psi-mi:“MI:0915”(physical association)	0.560
ADGRE2	MTERF3	psi-mi:“MI:0915”(physical association)	0.560
STX8	MTERF3	psi-mi:“MI:0915”(physical association)	0.560
ERG28	MTERF3	psi-mi:“MI:0915”(physical association)	0.560
MAL2	MTERF3	psi-mi:“MI:0915”(physical association)	0.560
SYP	MTERF3	psi-mi:“MI:0915”(physical association)	0.560
YIF1A	MTERF3	psi-mi:“MI:0915”(physical association)	0.560
SCAMP1	MTERF3	psi-mi:“MI:0915”(physical association)	0.560
FADS6	MTERF3	psi-mi:“MI:0915”(physical association)	0.560
MTERF3	SLC17A9	psi-mi:“MI:0915”(physical association)	0.560
HIGD1C	MTERF3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (417): MTERF3 (Two-hybrid), AGTRAP (Two-hybrid), CMTM5 (Two-hybrid), FUNDC1 (Two-hybrid), MTERF3 (Affinity Capture-MS), MTERF3 (Affinity Capture-MS), MTERF3 (Affinity Capture-MS), MTERF3 (Affinity Capture-MS), MTERF3 (Affinity Capture-MS), MTERF3 (Affinity Capture-MS), MTERF3 (Affinity Capture-MS), MTERF3 (Affinity Capture-MS), MTERF3 (Affinity Capture-MS), MTERF3 (Affinity Capture-MS), MTERF3 (Affinity Capture-MS)

ESM2 similar proteins: A2WX30, A2XEV1, A3BN26, B4F8Z1, B4FTR7, B6TGN4, B6TTV8, B8AK78, B9EJ57, F4I933, F4IHL3, Q01IJ3, Q0DVX2, Q0JCU7, Q0WUF6, Q10CI8, Q10PZ4, Q49AM1, Q5N800, Q5QLS7, Q5R6G1, Q5R9U8, Q5VRY0, Q5XIE2, Q5ZJC8, Q60EH4, Q65XL5, Q67UU0, Q6ATB4, Q6AUK6, Q6EUK7, Q6K9C1, Q6P6Q6, Q6Y9P5, Q6YSY5, Q7X745, Q7XAP4, Q84QA7, Q84X53, Q8BKY8

Diamond homologs: Q5ZJC8, Q6P6Q6, Q8R3J4, Q96E29, Q9VPD5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 157 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Mitochondrial ribosome-associated quality control	18	21.7×	4e-17
Mitochondrial translation initiation	16	19.9×	7e-15
Mitochondrial translation elongation	16	19.9×	7e-15
Mitochondrial translation	14	18.9×	9e-13
Transport of Mature Transcript to Cytoplasm	5	18.7×	2e-04
Mitochondrial translation termination	16	17.2×	6e-14
RNA Polymerase II Transcription Termination	5	10.8×	2e-03
Translation	17	10.3×	3e-11

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial large ribosomal subunit assembly	7	46.9×	2e-08
positive regulation of cytoplasmic translation	5	33.5×	3e-05
mitochondrial translation	17	20.0×	5e-15
regulation of alternative mRNA splicing, via spliceosome	8	13.2×	2e-05
mRNA stabilization	5	12.4×	3e-03
translation	14	9.7×	4e-08
mRNA transport	5	8.9×	9e-03
RNA processing	6	8.9×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1399 predictions. Top by Δscore:

Variant	Effect	Δscore
8:96244077:AAACC:A	acceptor_loss	1.0000
8:96244078:AACCT:A	acceptor_loss	1.0000
8:96244079:ACCTA:A	acceptor_loss	1.0000
8:96244080:CCTAA:C	acceptor_loss	1.0000
8:96244081:C:A	acceptor_loss	1.0000
8:96244082:T:G	acceptor_loss	1.0000
8:96245927:CTAGT:C	acceptor_gain	1.0000
8:96245938:T:C	acceptor_gain	1.0000
8:96245938:T:TC	acceptor_gain	1.0000
8:96246294:T:A	donor_gain	1.0000
8:96256957:CTTA:C	donor_loss	1.0000
8:96256958:TTAC:T	donor_loss	1.0000
8:96256959:TA:T	donor_loss	1.0000
8:96256960:A:AC	donor_gain	1.0000
8:96256960:AC:A	donor_gain	1.0000
8:96256961:C:CC	donor_gain	1.0000
8:96256961:CC:C	donor_gain	1.0000
8:96256961:CCTAG:C	donor_gain	1.0000
8:96257110:CAGTT:C	acceptor_gain	1.0000
8:96257112:GTT:G	acceptor_gain	1.0000
8:96257113:TT:T	acceptor_gain	1.0000
8:96257114:TCT:T	acceptor_loss	1.0000
8:96257115:C:CC	acceptor_gain	1.0000
8:96257116:T:C	acceptor_gain	1.0000
8:96257117:T:C	acceptor_gain	1.0000
8:96257117:T:TC	acceptor_gain	1.0000
8:96259270:T:TA	donor_gain	1.0000
8:96244076:TAAAC:T	acceptor_gain	0.9900
8:96245854:TCCTA:T	donor_loss	0.9900
8:96245855:CCTA:C	donor_loss	0.9900

AlphaMissense

2769 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:96239639:A:G	L369P	0.989
8:96244058:A:G	F307S	0.989
8:96239650:T:A	R365S	0.988
8:96239650:T:G	R365S	0.988
8:96239506:G:C	F413L	0.985
8:96239506:G:T	F413L	0.985
8:96239508:A:G	F413L	0.985
8:96245921:A:G	L279P	0.983
8:96246359:A:G	L258P	0.983
8:96246443:A:G	L230P	0.981
8:96239642:A:G	F368S	0.980
8:96246401:A:T	V244D	0.980
8:96250915:A:G	L223P	0.980
8:96239537:G:T	A403D	0.979
8:96239639:A:T	L369H	0.979
8:96246340:A:C	F264L	0.976
8:96246340:A:T	F264L	0.976
8:96246342:A:G	F264L	0.976
8:96239651:C:G	R365T	0.974
8:96246428:A:G	F235S	0.974
8:96246393:C:G	A247P	0.973
8:96239641:A:C	F368L	0.972
8:96239641:A:T	F368L	0.972
8:96239643:A:G	F368L	0.972
8:96239639:A:C	L369R	0.971
8:96245906:G:C	P284R	0.971
8:96246454:C:A	R226S	0.969
8:96246454:C:G	R226S	0.969
8:96245897:A:C	L287R	0.968
8:96245906:G:T	P284Q	0.968

dbSNP variants (sampled 300 via entrez): RS1000291831 (8:96260716 A>C), RS1000298839 (8:96254205 A>G), RS1000339743 (8:96251485 C>A), RS1000392704 (8:96258465 T>C), RS1000407665 (8:96261047 TAAAG>T), RS1000625100 (8:96253029 T>G), RS1000631169 (8:96253898 C>T), RS1000690243 (8:96251730 T>C), RS1001033635 (8:96240164 G>A,T), RS1001071410 (8:96248991 T>A), RS1001079881 (8:96252843 A>G), RS1001100537 (8:96241418 CAAAAA>C,CA,CAAAA,CAAAAAA), RS1001131780 (8:96247275 C>T), RS1001284315 (8:96241810 T>G), RS1001385056 (8:96240868 C>T)

Disease associations

OMIM: gene MIM:616930 | 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
GCST004691_8	Huntington’s disease progression	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008336	disease progression measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	affects cotreatment, increases expression	3
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
manganese chloride	increases abundance, increases expression	1
ochratoxin A	decreases acetylation, decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases expression, decreases reaction	1
benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone	decreases expression, decreases reaction	1
monomethylarsonous acid	decreases expression	1
K 7174	increases expression	1
abrine	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Temozolomide	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ammonium Chloride	decreases reaction, decreases expression	1
Chloroquine	decreases expression, decreases reaction	1
Cycloheximide	decreases expression, decreases reaction	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Diazinon	increases methylation	1
Diuron	decreases expression	1
Doxorubicin	increases expression	1
Formaldehyde	decreases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Manganese	increases abundance, increases expression	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XQ68	HAP1 MTERFD1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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