TEFM

Summary

TEFM (transcription elongation factor, mitochondrial, HGNC:26223) is a protein-coding gene on chromosome 17q11.2, encoding Transcription elongation factor, mitochondrial (Q96QE5). Transcription elongation factor which increases mitochondrial RNA polymerase processivity. It is a selective cancer dependency (DepMap: 39.7% of cell lines).

Enables transcription elongation factor activity. Involved in positive regulation of mitochondrial transcription and regulation of oxidative phosphorylation. Located in mitochondrial nucleoid. Part of ribonucleoprotein complex. Implicated in combined oxidative phosphorylation deficiency.

Source: NCBI Gene 79736 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined oxidative phosphorylation deficiency 58 (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 62 total
• Phenotypes (HPO): 50
• Cancer dependency (DepMap): dependent in 39.7% of screened cell lines
• MANE Select transcript: NM_024683

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26223
Approved symbol	TEFM
Name	transcription elongation factor, mitochondrial
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22729
Ensembl gene	ENSG00000172171
Ensembl biotype	protein_coding
OMIM	616422
Entrez	79736

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000306049, ENST00000541382, ENST00000579183, ENST00000580840, ENST00000581216, ENST00000876800, ENST00000876801, ENST00000876802

RefSeq mRNA: 1 — MANE Select: NM_024683 NM_024683

CCDS: CCDS42291

Canonical transcript exons

ENST00000581216 — 4 exons

Exon	Start	End
ENSE00001161648	30900413	30900562
ENSE00001161655	30904066	30904529
ENSE00001314265	30898986	30899606
ENSE00002730033	30906168	30906238

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 98.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.1597 / max 175.6751, expressed in 1767 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165198	10.0596	1763
165199	0.1002	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.10	gold quality
visceral pleura	UBERON:0002401	90.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.93	gold quality
cerebellar vermis	UBERON:0004720	89.66	gold quality
tendon	UBERON:0000043	89.62	gold quality
buccal mucosa cell	CL:0002336	89.03	gold quality
secondary oocyte	CL:0000655	88.81	gold quality
medial globus pallidus	UBERON:0002477	88.48	gold quality
tibia	UBERON:0000979	88.18	gold quality
pleura	UBERON:0000977	87.93	gold quality
parietal pleura	UBERON:0002400	87.83	gold quality
monocyte	CL:0000576	87.47	gold quality
trabecular bone tissue	UBERON:0002483	87.41	gold quality
oocyte	CL:0000023	87.21	gold quality
mononuclear cell	CL:0000842	87.13	gold quality
nipple	UBERON:0002030	87.08	gold quality
leukocyte	CL:0000738	86.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.36	gold quality
globus pallidus	UBERON:0001875	86.31	gold quality
calcaneal tendon	UBERON:0003701	86.21	gold quality
rectum	UBERON:0001052	85.80	gold quality
amniotic fluid	UBERON:0000173	84.70	gold quality
mucosa of transverse colon	UBERON:0004991	84.59	gold quality
Brodmann (1909) area 23	UBERON:0013554	84.49	gold quality
islet of Langerhans	UBERON:0000006	84.27	gold quality
corpus callosum	UBERON:0002336	83.97	gold quality
pylorus	UBERON:0001166	83.70	gold quality
lymph node	UBERON:0000029	83.37	gold quality
adrenal tissue	UBERON:0018303	83.27	gold quality
endometrium	UBERON:0001295	83.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting TEFM, 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-513B-5P	99.99	69.96	2150
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-4662A-5P	98.48	67.18	1007
HSA-MIR-610	96.84	67.98	905
HSA-MIR-4694-5P	94.62	65.39	532

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 39.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• The TEFM protein is proposed to be a critical component of the transcription apparatus of human mitochondria. (PMID:21278163)
• study found interaction of TEFM with mitochondrial RNA polymerase and nascent transcript prevents generation of replication primers and increases transcription processivity and serves as a molecular switch between replication and transcription, which appear to be mutually exclusive processes in mitochondria (PMID:25635099)
• Data indicate transcription elongation factor (TEFM) as an essential component of the mitochondrial transcription machinery. (PMID:25690892)
• Data provide insights into target specificity of TEFM and mechanisms by which it regulates the switch between transcription and replication of mitochondrial DNA. (PMID:29033127)
• Elevated TEFM expression promotes growth and metastasis through activation of ROS/ERK signaling in hepatocellular carcinoma. (PMID:33771980)
• TEFM variants impair mitochondrial transcription causing childhood-onset neurological disease. (PMID:36823193)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tefm	ENSDARG00000100548
mus_musculus	Tefm	ENSMUSG00000046909
rattus_norvegicus	Tefm	ENSRNOG00000004000
drosophila_melanogaster	CG14450	FBGN0037184

Protein

Protein identifiers

Transcription elongation factor, mitochondrial — Q96QE5 (reviewed: Q96QE5)

All UniProt accessions (2): Q96QE5, J3KTG7

UniProt curated annotations — full annotation on UniProt →

Function. Transcription elongation factor which increases mitochondrial RNA polymerase processivity. Regulates transcription of the mitochondrial genome, including genes important for the oxidative phosphorylation machinery.

Subunit / interactions. Interacts with POLRMT.

Subcellular location. Mitochondrion matrix. Mitochondrion nucleoid.

Disease relevance. Combined oxidative phosphorylation deficiency 58 (COXPD58) [MIM:620451] An autosomal recessive mitochondrial disease manifesting in the first 5 years of life and characterized by a wide range of clinical presentations. Clinical features include neonatal lactic acidosis, epileptic encephalopathy, developmental delay and impaired intellectual development with non-specific brain abnormalities, or mitochondrial myopathy with a treatable neuromuscular transmission defect. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TEFM family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96QE5-1	1	yes
Q96QE5-4	2

RefSeq proteins (1): NP_078959* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010994	RuvA_2-like	Homologous_superfamily
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR036397	RNaseH_sf	Homologous_superfamily
IPR039150	TEFM	Family

Pfam: PF12836

UniProt features (38 total): helix 16, strand 10, sequence variant 6, splice variant 2, transit peptide 1, chain 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
5OL9	X-RAY DIFFRACTION	1.3
5OL8	X-RAY DIFFRACTION	1.9
9BDC	ELECTRON MICROSCOPY	2.54
8U8V	ELECTRON MICROSCOPY	2.74
9BDD	ELECTRON MICROSCOPY	2.86
8U8U	ELECTRON MICROSCOPY	2.9
9MNA	ELECTRON MICROSCOPY	3.77
5OLA	X-RAY DIFFRACTION	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96QE5-F1	81.36	0.63

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 274 (showing top): GOMF_ENDONUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOBP_MITOCHONDRIAL_DNA_METABOLIC_PROCESS, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, chr17q11, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_REGULATION_OF_OXIDATIVE_PHOSPHORYLATION, WANG_LMO4_TARGETS_DN, GOBP_OXIDATIVE_PHOSPHORYLATION, GOBP_MITOCHONDRIAL_RNA_METABOLIC_PROCESS, GAZDA_DIAMOND_BLACKFAN_ANEMIA_ERYTHROID_UP, KIM_GERMINAL_CENTER_T_HELPER_UP, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN

GO Biological Process (3): regulation of oxidative phosphorylation (GO:0002082), transcription elongation by mitochondrial RNA polymerase (GO:0006392), positive regulation of mitochondrial transcription (GO:1903109)

GO Molecular Function (4): transcription elongation factor activity (GO:0003711), RNA binding (GO:0003723), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), mitochondrial nucleoid (GO:0042645), ribonucleoprotein complex (GO:1990904)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrial transcription	2
binding	2
mitochondrion	2
oxidative phosphorylation	1
regulation of aerobic respiration	1
mitochondrial RNA metabolic process	1
DNA-templated transcription elongation	1
positive regulation of DNA-templated transcription	1
regulation of mitochondrial transcription	1
transcription regulator activity	1
nucleic acid binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular organelle lumen	1
mitochondrial matrix	1
nucleoid	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

1180 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TEFM	POLRMT	O00411	952
TEFM	TFB2M	Q9H5Q4	770
TEFM	MTERF1	Q99551	734
TEFM	MRPL12	P52815	706
TEFM	CRLF3	Q8IUI8	702
TEFM	RAB11FIP4	Q86YS3	691
TEFM	TWNK	Q96RR1	680
TEFM	ATAD5	Q96QE3	678
TEFM	UTP6	Q9NYH9	672
TEFM	ADAP2	Q9NPF8	646
TEFM	COPRS	Q9NQ92	635
TEFM	TFAM	Q00059	625
TEFM	LRRC37B	Q96QE4	624
TEFM	EVI2A	P22794	609
TEFM	MTERF2	Q49AM1	603

IntAct

79 interactions, top by confidence:

A	B	Type	Score
INO80E	YY1	psi-mi:“MI:0914”(association)	0.900
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
TEFM	POLRMT	psi-mi:“MI:0914”(association)	0.560
POLRMT	TFAM	psi-mi:“MI:0914”(association)	0.560
POLRMT	TEFM	psi-mi:“MI:0915”(physical association)	0.560
ARIH1	SPOP	psi-mi:“MI:0914”(association)	0.530
KBTBD7	PLD2	psi-mi:“MI:0914”(association)	0.530
CD44	PDPK1	psi-mi:“MI:0914”(association)	0.530
RPL13	RRP8	psi-mi:“MI:0914”(association)	0.530
RPL4	TEFM	psi-mi:“MI:0914”(association)	0.530
NPM1	WDR46	psi-mi:“MI:0914”(association)	0.480
TEFM	E2	psi-mi:“MI:0915”(physical association)	0.370
Pcna	SIVA1	psi-mi:“MI:0914”(association)	0.350
Ccdc9	ACIN1	psi-mi:“MI:0914”(association)	0.350
KBTBD7	DKFZp686H10254	psi-mi:“MI:0914”(association)	0.350
KBTBD7	THOC2	psi-mi:“MI:0914”(association)	0.350
RPGRIP1L	NPHP1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
CD44	TCAF2	psi-mi:“MI:0914”(association)	0.350
SDC2	METTL8	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
GABARAP		psi-mi:“MI:0914”(association)	0.350

BioGRID (239): TEFM (Affinity Capture-MS), TEFM (Affinity Capture-MS), TEFM (Affinity Capture-MS), TEFM (Affinity Capture-MS), TEFM (Affinity Capture-MS), TEFM (Affinity Capture-MS), TEFM (Affinity Capture-MS), TEFM (Affinity Capture-MS), TEFM (Affinity Capture-MS), RPP25L (Affinity Capture-MS), TEFM (Affinity Capture-MS), TEFM (Affinity Capture-MS), TEFM (Affinity Capture-MS), TEFM (Affinity Capture-MS), TEFM (Affinity Capture-MS)

ESM2 similar proteins: A1L3L1, A2RT67, A3KPW7, A4IIA7, A8C750, A8C752, D2HNY3, E1BGQ2, E1C3P4, Q08CL8, Q08DZ8, Q0IHB3, Q149N8, Q1RMU2, Q1RMZ1, Q3MJ13, Q3T1H6, Q5F3F2, Q5RED8, Q5VVJ2, Q5ZJ87, Q66J91, Q69Z66, Q6AYF5, Q6DE97, Q6GR37, Q6P1E7, Q6PNC0, Q6YHU6, Q7TPQ3, Q8BKW4, Q8BXK4, Q8IWR0, Q8IYF3, Q8IZE3, Q8K2I9, Q8NA31, Q8NEN0, Q8NFZ0, Q96EW2

Diamond homologs: A6QPR9, Q0P4D6, Q4KM51, Q5SSK3, Q96QE5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 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
SRP-dependent cotranslational protein targeting to membrane	9	17.7×	4e-07
Peptide chain elongation	6	14.9×	1e-04
Viral mRNA Translation	6	14.9×	1e-04
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	6	14.8×	1e-04
Selenocysteine synthesis	6	14.1×	1e-04
Eukaryotic Translation Termination	6	14.1×	1e-04
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	6	13.8×	1e-04
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	6	13.8×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	8	20.9×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

676 predictions. Top by Δscore:

Variant	Effect	Δscore
17:30900407:CCTTA:C	donor_loss	1.0000
17:30900408:CTTA:C	donor_loss	1.0000
17:30900409:TTA:T	donor_loss	1.0000
17:30900410:TACCT:T	donor_loss	1.0000
17:30900412:C:T	donor_loss	1.0000
17:30900412:CCT:C	donor_gain	1.0000
17:30900528:G:GC	acceptor_gain	1.0000
17:30900532:C:CT	acceptor_gain	1.0000
17:30900532:C:T	acceptor_gain	1.0000
17:30900533:A:T	acceptor_gain	1.0000
17:30900559:CTGC:C	acceptor_gain	1.0000
17:30899608:T:C	acceptor_gain	0.9900
17:30899611:T:C	acceptor_gain	0.9900
17:30899611:T:TC	acceptor_gain	0.9900
17:30900563:CTAAA:C	acceptor_loss	0.9900
17:30900564:T:C	acceptor_loss	0.9900
17:30906169:T:TA	donor_gain	0.9900
17:30906197:ATCT:A	donor_gain	0.9900
17:30906198:T:C	donor_gain	0.9900
17:30906227:T:TA	donor_gain	0.9900
17:30906240:T:TA	donor_gain	0.9900
17:30900555:TTAA:T	acceptor_gain	0.9800
17:30900563:C:CC	acceptor_gain	0.9800
17:30900569:GAAAA:G	acceptor_loss	0.9800
17:30904525:CCTCT:C	acceptor_gain	0.9800
17:30904526:CTCTC:C	acceptor_gain	0.9800
17:30904527:TCTCT:T	acceptor_gain	0.9800
17:30906170:C:A	donor_gain	0.9800
17:30899607:C:CC	acceptor_gain	0.9700
17:30904061:TATAC:T	donor_loss	0.9700

AlphaMissense

2353 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:30900478:A:G	W194R	0.993
17:30900478:A:T	W194R	0.993
17:30899213:C:G	A347P	0.991
17:30900517:C:G	A181P	0.990
17:30899392:A:G	L287P	0.989
17:30899563:A:T	V230D	0.989
17:30900514:A:G	W182R	0.988
17:30900514:A:T	W182R	0.988
17:30900543:G:A	S172F	0.987
17:30900516:G:T	A181D	0.985
17:30900543:G:T	S172Y	0.985
17:30904331:A:G	L77S	0.984
17:30899218:A:G	L345S	0.983
17:30899397:A:C	F285L	0.983
17:30899397:A:T	F285L	0.983
17:30899399:A:G	F285L	0.983
17:30904252:T:A	R103S	0.983
17:30904252:T:G	R103S	0.983
17:30900511:C:G	A183P	0.980
17:30900504:A:G	L185P	0.979
17:30899489:C:G	A255P	0.978
17:30900486:A:T	V191E	0.978
17:30899206:G:T	A349D	0.977
17:30899207:C:G	A349P	0.977
17:30899557:T:A	E232V	0.977
17:30899374:C:G	R293P	0.976
17:30899482:A:G	L257P	0.976
17:30900544:A:G	S172P	0.975
17:30904327:A:C	N78K	0.974
17:30904327:A:T	N78K	0.974

dbSNP variants (sampled 300 via entrez): RS1000045614 (17:30906490 G>A), RS1000258870 (17:30902909 G>A), RS1000290134 (17:30902447 A>G,T), RS1001011906 (17:30905229 G>A,T), RS1001902773 (17:30901491 A>C), RS1002733634 (17:30901823 C>A,G), RS1003199011 (17:30905913 C>A), RS1003460778 (17:30908137 G>A), RS1003533033 (17:30907701 A>G), RS1003799221 (17:30907272 G>C), RS1003938916 (17:30899148 T>C), RS1004145509 (17:30900543 G>T), RS1004150574 (17:30905911 C>G), RS1004344277 (17:30900090 T>G), RS1004492247 (17:30907655 C>G,T)

Disease associations

OMIM: gene MIM:616422 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
combined oxidative phosphorylation deficiency 58	Strong	Autosomal recessive

Mondo (1): combined oxidative phosphorylation deficiency 58 (MONDO:0957537)

Orphanet (0):

HPO phenotypes

50 total (30 of 50 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000369	Low-set ears
HP:0000426	Prominent nasal bridge
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000572	Visual loss
HP:0000597	Ophthalmoparesis
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001324	Muscle weakness
HP:0001336	Myoclonus
HP:0001943	Hypoglycemia
HP:0002013	Vomiting
HP:0002066	Gait ataxia
HP:0002069	Bilateral tonic-clonic seizure
HP:0002151	Increased circulating lactate concentration
HP:0002171	Gliosis
HP:0002267	Exaggerated startle response
HP:0003155	Elevated circulating alkaline phosphatase concentration
HP:0003200	Ragged-red muscle fibers
HP:0003348	Hyperalaninemia
HP:0003403	EMG: decremental response of compound muscle action potential to repetitive nerve stimulation

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008163_473	Height	5.000000e-07
GCST90000050_75	Age at first birth	5.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009101	age at first birth measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydrogen Peroxide	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Ribonucleotides	affects binding	1
Theophylline	affects cotreatment, increases expression	1
Urethane	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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