TFAM

Summary

TFAM (transcription factor A, mitochondrial, HGNC:11741) is a protein-coding gene on chromosome 10q21.1, encoding Transcription factor A, mitochondrial (Q00059). Binds to the mitochondrial light strand promoter and functions in mitochondrial transcription regulation. It is a selective cancer dependency (DepMap: 65.1% of cell lines).

This gene encodes a key mitochondrial transcription factor containing two high mobility group motifs. The encoded protein also functions in mitochondrial DNA replication and repair. Sequence polymorphisms in this gene are associated with Alzheimer’s and Parkinson’s diseases. There are pseudogenes for this gene on chromosomes 6, 7, and 11. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 7019 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial DNA depletion syndrome 15 (hepatocerebral type) (Strong, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 107 total — 2 likely-pathogenic
• GTEx eGene: eQTL in 40 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 28
• Cancer dependency (DepMap): dependent in 65.1% of screened cell lines
• Constraint (gnomAD): pLI 0.09 (LoF-tolerant), LOEUF 0.74 (unconstrained)
• Transcription factor: yes — 17 downstream targets (CollecTRI)
• MANE Select transcript: NM_003201
• Interaction hub: 3,244 STRING partners (top 2% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11741
Approved symbol	TFAM
Name	transcription factor A, mitochondrial
Location	10q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000108064
Ensembl biotype	protein_coding
OMIM	600438
Entrez	7019

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 9 protein_coding, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000487519

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

ENST00000487519, ENST00000373895, ENST00000373899, ENST00000395377, ENST00000909231, ENST00000935269, ENST00000935270, ENST00000974633, ENST00001086983, ENST00001086985, ENST00001098393, ENST00001098394, ENST00001098395, ENST00001130143, ENST00001141739

RefSeq mRNA: 2 — MANE Select: NM_003201 NM_001270782, NM_003201

CCDS: CCDS59217, CCDS7253

Canonical transcript exons

ENST00000487519 — 7 exons

Exon	Start	End
ENSE00001849163	58394928	58399220
ENSE00001854885	58385410	58385648
ENSE00003493428	58394358	58394414
ENSE00003599654	58388670	58388819
ENSE00003628587	58390765	58390860
ENSE00003665581	58388190	58388260
ENSE00003667136	58386220	58386338

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 95.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.1160 / max 813.3107, expressed in 1821 samples.

Highest expression (Bgee): testis, secondary oocyte, calcaneal tendon, adrenal tissue, ventricular zone.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TFAM is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 40 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 42 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	6.9e-37	-0.30	10:58385319:A:G
Esophagus Muscularis	eqtl	1.1e-28	-0.26	10:58385319:A:G
Nerve Tibial	eqtl	2.2e-27	-0.26	10:58385319:A:G
Brain Cerebellar Hemisphere	eqtl	2.0e-18	-0.38	10:58386082:GTC:G
Adipose Subcutaneous	eqtl	3.1e-18	-0.20	10:58385319:A:G
Thyroid	eqtl	1.7e-16	-0.17	10:58385319:A:G
Esophagus Gastroesophageal Junction	eqtl	1.8e-16	-0.27	10:58385319:A:G
Brain Nucleus accumbens basal ganglia	eqtl	3.5e-16	-0.41	10:58396406:A:G
Artery Aorta	eqtl	4.1e-16	-0.21	10:58385319:A:G
Esophagus Mucosa	eqtl	3.5e-13	+0.16	10:58386082:GTC:G
Heart Atrial Appendage	eqtl	5.2e-13	-0.25	10:58386082:GTC:G
Brain Cerebellum	eqtl	2.7e-12	-0.29	10:58401412:G:A
Colon Sigmoid	eqtl	1.4e-11	-0.18	10:58385319:A:G
Skin Sun Exposed Lower leg	eqtl	2.4e-11	+0.16	10:58385238:C:A
Heart Left Ventricle	eqtl	4.1e-11	-0.25	10:58395360:G:T
Pituitary	eqtl	4.5e-11	-0.25	10:58385319:A:G
Cells Cultured fibroblasts	eqtl	2.0e-10	-0.10	10:58385124:C:T
Brain Caudate basal ganglia	eqtl	3.4e-10	-0.30	10:58385837:G:C
Brain Anterior cingulate cortex BA24	eqtl	7.8e-10	-0.43	10:58396406:A:G
Adrenal Gland	eqtl	9.8e-10	-0.21	10:58385319:A:G

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
104998	52.0816	1821
104999	1.7572	799
104995	0.1466	48
104997	0.1053	27
104996	0.0253	6

Top tissues by expression

showing 100 of 293 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	95.53	gold quality
left testis	UBERON:0004533	95.37	gold quality
secondary oocyte	CL:0000655	94.52	gold quality
testis	UBERON:0000473	94.24	gold quality
calcaneal tendon	UBERON:0003701	92.65	gold quality
adrenal tissue	UBERON:0018303	92.63	gold quality
ventricular zone	UBERON:0003053	91.64	gold quality
monocyte	CL:0000576	91.49	gold quality
germinal epithelium of ovary	UBERON:0001304	91.38	gold quality
tendon	UBERON:0000043	91.36	gold quality
mononuclear cell	CL:0000842	90.96	gold quality
ganglionic eminence	UBERON:0004023	90.93	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.78	gold quality
leukocyte	CL:0000738	90.76	gold quality
oocyte	CL:0000023	90.66	gold quality
medial globus pallidus	UBERON:0002477	90.51	gold quality
lymph node	UBERON:0000029	89.99	gold quality
rectum	UBERON:0001052	89.65	gold quality
islet of Langerhans	UBERON:0000006	89.35	gold quality
globus pallidus	UBERON:0001875	89.12	gold quality
cortical plate	UBERON:0005343	89.06	gold quality
tonsil	UBERON:0002372	88.64	gold quality
vermiform appendix	UBERON:0001154	88.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.38	gold quality
caecum	UBERON:0001153	88.37	gold quality
colonic mucosa	UBERON:0000317	88.32	gold quality
parietal pleura	UBERON:0002400	88.16	gold quality
embryo	UBERON:0000922	88.03	gold quality
body of tongue	UBERON:0011876	87.90	gold quality
amniotic fluid	UBERON:0000173	87.87	gold quality
bone marrow	UBERON:0002371	87.77	gold quality
pericardium	UBERON:0002407	87.54	gold quality
tendon of biceps brachii	UBERON:0008188	87.29	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	87.13	gold quality
nephron tubule	UBERON:0001231	86.80	gold quality
pleura	UBERON:0000977	86.60	gold quality
endometrium	UBERON:0001295	86.54	gold quality
palpebral conjunctiva	UBERON:0001812	86.47	gold quality
muscle of leg	UBERON:0001383	86.31	gold quality
vena cava	UBERON:0004087	86.30	silver quality
pylorus	UBERON:0001166	86.29	gold quality
gastrocnemius	UBERON:0001388	86.25	gold quality
adrenal gland	UBERON:0002369	85.93	gold quality
duodenum	UBERON:0002114	85.91	gold quality
pons	UBERON:0000988	85.88	gold quality
smooth muscle tissue	UBERON:0001135	85.84	gold quality
right adrenal gland cortex	UBERON:0035827	85.72	gold quality
tongue	UBERON:0001723	85.64	gold quality
pharyngeal mucosa	UBERON:0000355	85.63	gold quality
mammary duct	UBERON:0001765	85.62	gold quality
right adrenal gland	UBERON:0001233	85.53	gold quality
visceral pleura	UBERON:0002401	85.48	gold quality
left adrenal gland	UBERON:0001234	85.47	gold quality
choroid plexus epithelium	UBERON:0003911	85.44	gold quality
adrenal cortex	UBERON:0001235	85.24	gold quality
nipple	UBERON:0002030	85.24	gold quality
epithelium of mammary gland	UBERON:0003244	85.22	gold quality
thoracic mammary gland	UBERON:0005200	85.18	gold quality
ovary	UBERON:0000992	85.17	gold quality
superior surface of tongue	UBERON:0007371	85.16	gold quality
mammary gland	UBERON:0001911	85.15	gold quality
left adrenal gland cortex	UBERON:0035825	85.11	gold quality
colonic epithelium	UBERON:0000397	84.99	gold quality
muscle organ	UBERON:0001630	84.97	gold quality
liver	UBERON:0002107	84.91	gold quality
corpus callosum	UBERON:0002336	84.89	gold quality
esophagus squamous epithelium	UBERON:0006920	84.87	gold quality
placenta	UBERON:0001987	84.79	gold quality
bone marrow cell	CL:0002092	84.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.63	gold quality
epithelial cell of pancreas	CL:0000083	84.54	gold quality
cardia of stomach	UBERON:0001162	84.51	gold quality
gall bladder	UBERON:0002110	84.36	gold quality
cartilage tissue	UBERON:0002418	84.31	gold quality
pancreas	UBERON:0001264	84.27	gold quality
heart left ventricle	UBERON:0002084	84.20	gold quality
cardiac ventricle	UBERON:0002082	84.19	gold quality
fallopian tube	UBERON:0003889	84.03	gold quality
biceps brachii	UBERON:0001507	83.92	gold quality
type B pancreatic cell	CL:0000169	83.91	gold quality
epithelium of esophagus	UBERON:0001976	83.87	gold quality
renal medulla	UBERON:0000362	83.79	gold quality
gingival epithelium	UBERON:0001949	83.77	gold quality
heart	UBERON:0000948	83.67	gold quality
skeletal muscle tissue	UBERON:0001134	83.62	gold quality
ventral tegmental area	UBERON:0002691	83.60	gold quality
jejunal mucosa	UBERON:0000399	83.59	gold quality
jejunum	UBERON:0002115	83.57	gold quality
peritoneum	UBERON:0002358	83.52	gold quality
omental fat pad	UBERON:0010414	83.49	gold quality
saphenous vein	UBERON:0007318	83.48	gold quality
adipose tissue of abdominal region	UBERON:0007808	83.45	gold quality
squamous epithelium	UBERON:0006914	83.42	gold quality
female reproductive system	UBERON:0000474	83.41	gold quality
oviduct epithelium	UBERON:0004804	83.38	gold quality
large intestine	UBERON:0000059	83.36	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.29	gold quality
subthalamic nucleus	UBERON:0001906	83.25	gold quality
triceps brachii	UBERON:0001509	83.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.81

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	35.9	low
Frontal cortex	tissue	30.9
Testis	tissue	30.8	medium
Caudate putamen	tissue	29.7
Lymph node	tissue	25.8	medium
Thymus	tissue	23.2
Tonsil	tissue	21.6	medium
Liver	tissue	21.2	low
Midbrain	tissue	20.9
Septum	tissue	20.9
Thalamus	tissue	20.6
Appendix	tissue	20.4	medium
Kidney	tissue	20.1	medium
Medulla oblongata	tissue	20.0
Spinal cord	tissue	19.9
Duodenum	tissue	19.8	medium
Corpus callosum	tissue	19.8
Postcentral gyrus	tissue	19.8
Pons	tissue	19.7
Putamen	tissue	19.7
Superior colliculi	tissue	19.7
Ventral forebrain	tissue	19.3
Placenta	tissue	19.1	medium
Substantia nigra	tissue	18.9
Adrenal gland	tissue	18.9	medium
Colon	tissue	18.7	medium
Hypothalamus	tissue	18.4
Thyroid gland	tissue	18.3	medium
Hippocampal formation	tissue	17.9
Periaqueductal gray	tissue	17.6
Basal ganglia	tissue	17.4	medium
Heart muscle	tissue	17.3	medium
Cerebral cortex	tissue	17.2	medium
Somatosensory cortex	tissue	17.2
Choroid plexus	tissue	16.8
Small intestine	tissue	16.7	medium
Skeletal muscle	tissue	16.6	low
Occipital cortex	tissue	16.6
Olfactory bulb	tissue	16.4
Salivary gland	tissue	16.3	medium
Spleen	tissue	16.3	medium
Breast	tissue	16.2	high
Rectum	tissue	16.2	medium
Cerebellum	tissue	15.8	medium
Motor cortex	tissue	15.7
Urinary bladder	tissue	15.6	medium
Adipose tissue	tissue	15.4	not detected
Retrosplenial cortex	tissue	15.3
Parathyroid gland	tissue	15.2	medium
Stomach 1	tissue	15.1	medium
Tongue	tissue	15.1
Nucleus accumbens	tissue	15.1
Entorhinal cortex	tissue	15.0
Retrosplenial and cingulate cortex	tissue	14.8
Amygdala	tissue	14.6
Prefrontal cortex	tissue	14.5
Ovary	tissue	14.5	low
Locus coeruleus	tissue	14.3
Temporal cortex	tissue	14.3
Insular cortex	tissue	14.0

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Cerebellar cortex (25.0), Vermis (23.0), Flocculonodular lobe (21.6), Corpus callosum, genu (white matter) (20.2), Ventral spinal cord (19.9).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

17 targets:

Target	Regulation
ACADM	Unknown
ATP2A2
AVPR2
BCL2L1
BIRC5
GFM1
GHRHR
HSP90B2P
HSPA4
INS
MT-CO1
NOS2
NRF1
SLC25A5
TFAM
TFB1M
UCP1	Activation

Upstream regulators (CollecTRI, top): E2F4, FOXC1, MYC, NFE2L2, NRF1, PDX1, PPARG, PPARGC1A, TFAM, ZNF143

miRNA regulators (miRDB)

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

showing 30 of 167 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4481	100.00	66.42	1669
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502

Functional genomics

gnomAD constraint: pLI 0.0868, LOEUF 0.742, missense Z 1.19 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000487519 — one region, missense o/e 0.79. DepMap (CRISPR cell-line fitness): dependent in 65.1% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): FU97 (-2.309), NCI-H1437 (-1.521), MEL-HO (-1.42), SU-DHL-10 (-1.307), MCF-7 (-1.265), LP-1 (-1.25), SNU-398 (-1.241), SNU-761 (-1.218), RERF-GC-1B (-1.204), NCI-H841 (-1.183), SNU-1076 (-1.169), HCC2429 (-1.14), KNS-81 (-1.11), TE-11 (-1.105), NCI-H1581 (-1.101).

Literature-anchored findings (GeneRIF, showing 40)

• the effects of mitochondrial transcription factor A (TFAM) and single-stranded DNA-binding protein (mtSSB) on D-loops (PMID:11964388)
• mtTFA plays an important role in the recognition of oxidative DNA damage. (PMID:12127986)
• both the mitochondrial transcription factor TFAM and mitochondrial single-stranded DNA-binding protein colocalize with Twinkle in intramitochondrial foci (PMID:12686611)
• Tfam interacts with p53 protein and helps regulate DNA damage. (PMID:12839966)
• TFB1 interacts with the C-terminal activation region of h-mtTFA and stimulates transcription independently of its RNA methyltransferase activity (PMID:12897151)
• This study describe a family with autosomal dominant progressive external ophthalmoplegia caused by a novel heterozygous A to C transversion at nucleotide 956 of the Twinkle gene. (PMID:12921794)
• There was an association of genotype rs1937G/G with Alzheimer disease in females and an association of a TFAM haplotype with Alzheimer disease both in the whole sample and in females. (PMID:15464268)
• mtDNA amount is finely correlated with the amount of TFAM but not with the transcription level (PMID:15509786)
• TFAM induces a structural change of the promoter that is required for POLRMT-dependent promoter recognition (PMID:15526033)
• Overexpression of mitochondrial transcription factor A (TFAM) stimulates mitochondrial DNA transcription, but is not sufficient to stimulate mitochondrial DNA replication. (PMID:15547250)
• Overexpression of TFAM in transgenic mice inhibited left ventricular remodeling after myocardial infarct and may provide a novel therapeutic strategy of cardiac failure. (PMID:16043643)
• we have determined its chromosomal localization, suggesting that its locus is highly conserved; we have searched for the presence of the delta5 isoform, demonstrating that it is present only in hominids (PMID:16202542)
• PDIP38 is located in the mitochondrial matrix. TFAM and mitochondrial single-stranded DNA binding protein (mtSSB) are co-immunoprecipitated with PDIP38 (PMID:16428295)
• These results suggest that PGC-1alpha variants with Gly/Gly at 482nd amino acid may impair the Tfam transcription, a regulatory function of mitochondrial biogenesis, resulting in dysfunctional mtDNA replication. (PMID:16631115)
• the C-terminal tail of TFAM is important for the strong general binding to mtDNA; this strong DNA-binding conferred by the C-tail may play an important role in the nucleoid structure (PMID:17167045)
• We have determined whether POLG and TFAM have functional roles in post-ejaculatory sperm mtDNA. (PMID:17339235)
• Three polymorphisms in the TFAM gene rs1937, rs2306604 and rs1049432 do not predict endurance capacity/trainability in Chinese males. (PMID:17497594)
• rs2306604 A-allele of mitochondrial transcription factor A could be a moderate risk factor for Alzheimer’s diseae (PMID:17537576)
• Transcription factor ZNF143 is required for expression of TFAM gene. (PMID:17707600)
• Data suggested that the mitochondrial targeting sequence of hTFAM may extend beyond the cleavable presequence. (PMID:18028422)
• TFAM-variants did not contribute to the risk of developing Parkinson disease (PMID:18248889)
• PHB1 maintains the organization and copy number of the mtDNA through both TFAM-independent and -dependent pathways. (PMID:18258228)
• The nigral dopamine neurons of MitoPark mice show respiratory chain dysfunction, accompanied by the development of intraneuronal inclusions and cell death. In early adulthood, the mice show progressing loss of motor function. (PMID:18642640)
• Overexpression of TFAM is therefore considered to ameliorate age-dependent impairment of the brain functions through the prevention of oxidative stress and mitochondrial dysfunctions in microglia. (PMID:18716221)
• determined the variation in the TFAM, TFB1M, and TFB2M genes in cardiac hypertrophy (PMID:19096125)
• Data show that overexpression of delta 5Tfam causes an increase of mitochondrial transcription, so also this isoform as a role in the mitochondrial process. (PMID:19192634)
• The X-ray crystal structure of h-mtTFA box B, revealed the features of a noncanonical HMG box. (PMID:19304746)
• Data suggest that Tfam overexpression protects mitochondria against Abeta-induced oxidative damage in SH-SY5Y cells. (PMID:19496804)
• On supercoiled templates, the promoter-independent activity was strongly suppressed by a putatively physiological amount of TFAM, while promoter-dependent transcription was inhibited to a lesser extent. (PMID:19624753)
• TFAM protein levels are higher in conditions with enhanced oxidative capacity (PMID:19681768)
• These results suggest that TRX2 not only functions as an antioxidant, but also supports mtTFA functions (PMID:19885567)
• Potentially functional polymorphic TFAM variants might influence PD risk alone or depending on mitochondrial haplogroup/haplogroup cluster background. (PMID:19925850)
• Our findings suggest a potential role of promoter TFAM methylation in the pathogenesis of insulin resistance in adolescents. (PMID:20202876)
• only two essential initiation factors, TFAM and TFB2M, and two promoters, LSP and HSP1, are required to drive transcription of the mitochondrial genome (PMID:20410300)
• TFAM gene Ser12Thr polymorphism is associated with physical performance of athletes. (PMID:20432700)
• POLG expression was related to decreased mtDNA copy number, and its overexpression associated with TFAM expression levels also have an impact on long-term survival among GBM type diffusely infiltrating astrocytomas patients. (PMID:20643228)
• TFAM modulates mitochondrial base excision repair by virtue of its DNA binding activity and protein interactions. (PMID:20739229)
• We found four common TFAM polymorphisms, with allele/genotype frequencies that did not differ between early onset myocardial infarction patients and controls. (PMID:20863902)
• This study provides the evidence that variations in TFAM are involved in the pathogenesis of sporadic LOAD in the Han Chinese population. (PMID:20977898)
• comparison between the 5’UTR length and the distribution of the different transcripts showed that the transcripts with the shortest TFAM 5’UTR are present in all the investigated tissues, while the longest 5’UTR seems to be related to tissue-specificity (PMID:21081181)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tfam	ENSDARG00000063145
mus_musculus	Tfam	ENSMUSG00000003923
rattus_norvegicus	Tfam	ENSRNOG00000000613
caenorhabditis_elegans	hmg-3	WBGENE00001973
caenorhabditis_elegans		WBGENE00001974

Paralogs (20): HMGB3 (ENSG00000029993), HMG20B (ENSG00000064961), SP100 (ENSG00000067066), SMARCE1 (ENSG00000073584), SP140 (ENSG00000079263), TOX4 (ENSG00000092203), HMGXB4 (ENSG00000100281), TOX3 (ENSG00000103460), UBTF (ENSG00000108312), HMGB1P1 (ENSG00000124097), TOX2 (ENSG00000124191), SP110 (ENSG00000135899), HMG20A (ENSG00000140382), SSRP1 (ENSG00000149136), HMGB2 (ENSG00000164104), HMGB4 (ENSG00000176256), SP140L (ENSG00000185404), HMGB1 (ENSG00000189403), TOX (ENSG00000198846), UBTFL1 (ENSG00000255009)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:107810) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 76 distinct phenotype terms.

Mouse phenotype (MP)	Records
premature death	6
abnormal respiratory electron transport chain	5
decreased body size	3
decreased mitochondrial DNA content	3
postnatal growth retardation	2
neurodegeneration	2
dilated heart left ventricle	2
increased heart weight	2
bradykinesia	2
axon degeneration	2
abnormal blood flow velocity	1
abnormal vascular development	1
abnormal heart development	1
enlarged heart	1
decreased hair follicle number	1
abnormal colon morphology	1
abnormal small intestine morphology	1
abnormal liver development	1
absent sebaceous gland	1
muscle spasm	1
tremors	1
abnormal enteric neuron morphology	1
abnormal PNS glial cell morphology	1
thick epidermis	1
weight loss	1

+51 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q0II87	91.4%	Diamond
Sus scrofa	Q5D144	91.4%	Diamond
Trachypithecus cristatus	Q4H0T5	91.0%	Diamond
Arabidopsis thaliana	P93047	86.1%	Diamond
Tetrahymena thermophila	P11873	73.7%	Diamond
Tetrahymena pyriformis	P40625	73.7%	Diamond
Saccharomyces cerevisiae S288C	P33417	44.2%	Diamond
Tetrahymena thermophila SB210	P40631	41.9%	Diamond

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
UBE2D1	protein-coding	7321
BICC1	protein-coding	80114
CISD1	protein-coding	55847
IPMK	protein-coding	253430

Protein

Protein identifiers

Transcription factor A, mitochondrial — Q00059 (reviewed: Q00059)

Alternative names: Mitochondrial transcription factor 1, Transcription factor 6, Transcription factor 6-like 2

All UniProt accessions (3): Q00059, E5KSU5, H7BYN3

UniProt curated annotations — full annotation on UniProt →

Function. Binds to the mitochondrial light strand promoter and functions in mitochondrial transcription regulation. Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT that is required for basal transcription of mitochondrial DNA. In this complex, TFAM recruits POLRMT to a specific promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand. Required for accurate and efficient promoter recognition by the mitochondrial RNA polymerase. Promotes transcription initiation from the HSP1 and the light strand promoter by binding immediately upstream of transcriptional start sites. Is able to unwind DNA. Bends the mitochondrial light strand promoter DNA into a U-turn shape via its HMG boxes. Required for maintenance of normal levels of mitochondrial DNA. May play a role in organizing and compacting mitochondrial DNA.

Subunit / interactions. Monomer; binds DNA as a monomer. Homodimer. Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT. In this complex TFAM recruits POLRMT to the promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand. Upon metabolic stress, forms a complex composed of FOXO3, SIRT3, TFAM and POLRMT. Interacts with TFB1M and TFB2M. Interacts with CLPX; this enhances DNA-binding.

Subcellular location. Mitochondrion. Mitochondrion matrix. Mitochondrion nucleoid.

Post-translational modifications. Phosphorylation by PKA within the HMG box 1 impairs DNA binding and promotes degradation by the AAA+ Lon protease.

Disease relevance. Mitochondrial DNA depletion syndrome 15, hepatocerebral type (MTDPS15) [MIM:617156] An autosomal recessive mitochondrial disorder characterized by severe intrauterine growth restriction, neonatal-onset hypoglycemia and liver dysfunction, mitochondrial DNA depletion in liver and skeletal muscle, and abnormal mitochondrial morphology observed in skeletal muscle. Hepatic pathology includes cirrhosis, steatosis and cholestasis. Progression to liver failure and death is rapid with no evidence of neurological impairment or other organ involvement. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Binds DNA via its HMG boxes. When bound to the mitochondrial light strand promoter, bends DNA into a U-turn shape, each HMG box bending the DNA by 90 degrees.

Isoforms (2)

UniProt ID	Names	Canonical?
Q00059-1	1	yes
Q00059-2	2

RefSeq proteins (2): NP_001257711, NP_003192* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009071	HMG_box_dom	Domain
IPR036910	HMG_box_dom_sf	Homologous_superfamily
IPR050342	HMGB	Family

Pfam: PF00505, PF09011

UniProt features (32 total): helix 11, modified residue 7, sequence variant 2, mutagenesis site 2, DNA-binding region 2, strand 2, site 2, transit peptide 1, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

16 structures by resolution:

PDB	Title	Method	Resolution (Å)
3FGH	Human mitochondrial transcription factor A box B	X-RAY DIFFRACTION	1.35
3TQ6	Crystal structure of human mitochondrial transcription factor A, TFAM or mtTFA, bound to …	X-RAY DIFFRACTION	2.45
3TMM	TFAM imposes a U-turn on mitochondrial DNA	X-RAY DIFFRACTION	2.5
7LBX	Crystal structure of TFAM (mitochondrial transcription factor A) in complex with LSP	X-RAY DIFFRACTION	2.7
4NNU	Distinct structural features of TFAM drive mitochondrial DNA packaging versus …	X-RAY DIFFRACTION	2.81
7LBW	Crystal structure of TFAM (mitochondrial transcription factor A) bridging two …	X-RAY DIFFRACTION	2.84
4NOD	Distinct structural features of TFAM drive mitochondrial DNA packaging versus …	X-RAY DIFFRACTION	2.9
9MN5	Structure of the human mitochondrial open transcription initiation complex, IC0	ELECTRON MICROSCOPY	3.04
6HB4	TFAM in Complex with Site-Y	X-RAY DIFFRACTION	3.05
9MN4	Structure of the human mitochondrial initially transcribing complex, IC3	ELECTRON MICROSCOPY	3.05
6HC3	TFAM bound to Site-X	X-RAY DIFFRACTION	3.1
9R96	Cryo-EM structure of the human mitochondrial RNA polymerase transcription initiation …	ELECTRON MICROSCOPY	3.1
9R95	Cryo-EM structure of the human mitochondrial RNA polymerase transcription initiation …	ELECTRON MICROSCOPY	3.2
9GZM	Cryo-EM structure of the human mitochondrial RNA polymerase transcription initiation …	ELECTRON MICROSCOPY	3.4
6ERQ	Structure of the human mitochondrial transcription initiation complex at the HSP promoter	X-RAY DIFFRACTION	4.5
6ERP	Structure of the human mitochondrial transcription initiation complex at the LSP promoter	X-RAY DIFFRACTION	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q00059-F1	86.06	0.78

Human Protein Atlas

Protein class: Predicted intracellular proteins, Transcription factors, Other all-alpha-helical DNA-binding domains, Disease related genes, Human disease related genes, Congenital disorders of metabolism, 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.

Catalytic / active sites (2)

Position	Role
58	intercalates between bases and promotes dna bending
182	intercalates between bases and promotes dna bending

Post-translational modifications (7)

Type	Positions
Phosphoserine	160, 193, 195, 55, 56, 61
Phosphothreonine	122

Mutagenesis-validated functional residues (2)

Position	Phenotype
77	moderate reduction in dna bending.
162	moderate reduction in dna bending.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-9837999	Mitochondrial protein degradation	curated
R-HSA-163282	Mitochondrial transcription initiation	curated
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-1592230	Mitochondrial biogenesis	—
R-HSA-1852241	Organelle biogenesis and maintenance	—
R-HSA-75944	Transcription from mitochondrial promoters	—
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis	electronic

MSigDB gene sets: 278 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, chr10q21, PUJANA_CHEK2_PCC_NETWORK, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_RESPONSE_TO_OXYGEN_LEVELS, KEGG_HUNTINGTONS_DISEASE, GOBP_MITOCHONDRIAL_RNA_METABOLIC_PROCESS, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GARY_CD5_TARGETS_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_UP, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS

GO Biological Process (4): response to hypoxia (GO:0001666), mitochondrial transcription (GO:0006390), transcription initiation at mitochondrial promoter (GO:0006391), response to nutrient (GO:0007584)

GO Molecular Function (9): mitochondrial promoter sequence-specific DNA binding (GO:0001018), transcription coactivator binding (GO:0001223), chromatin binding (GO:0003682), RNA binding (GO:0003723), heat shock protein binding (GO:0031072), mitochondrial transcription factor activity (GO:0034246), sequence-specific DNA binding (GO:0043565), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), protein-containing complex (GO:0032991), mitochondrial nucleoid (GO:0042645)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Transcription from mitochondrial promoters	1
Mitochondrial biogenesis	1
Metabolism of proteins	1
Organelle biogenesis and maintenance	1
Gene expression (Transcription)	1

GO top-level categories

27 GO namespaces:

Category	Terms
mitochondrion	4
mitochondrial RNA metabolic process	2
mitochondrial transcription	2
binding	2
nucleic acid binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
response to stress	1
response to decreased oxygen levels	1
DNA-templated transcription	1
mitochondrial gene expression	1
DNA-templated transcription initiation	1
response to nutrient levels	1
response to chemical	1
transcription cis-regulatory region binding	1
transcription coregulator binding	1
protein binding	1
mitochondrial single-subunit type RNA polymerase binding	1
mitochondrial promoter sequence-specific DNA binding	1
transcription regulator activity	1
DNA binding	1
intracellular organelle lumen	1
cellular anatomical structure	1
cellular_component	1
mitochondrial matrix	1
nucleoid	1
intracellular membraneless organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 12 of 19 annotations. The rest are phylogenetic / computational / electronic (IEA).

12 experimentally-supported GO terms:

GO term	NS	Evidence
mitochondrial transcription	BP	direct assay
transcription initiation at mitochondrial promoter	BP	direct assay
mitochondrial matrix	CC	direct assay
mitochondrial nucleoid	CC	direct assay
mitochondrion	CC	direct assay
nucleus	CC	high-throughput assay
protein-containing complex	CC	direct assay
RNA binding	MF	high-throughput assay
chromatin binding	MF	direct assay
mitochondrial promoter sequence-specific DNA binding	MF	direct assay
mitochondrial transcription factor activity	MF	mutant phenotype
sequence-specific DNA binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 3,244 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TFAM	TFB2M	Q9H5Q4	975
TFAM	POLRMT	O00411	975
TFAM	TFB1M	Q8WVM0	965
TFAM	NRF1	Q16656	962
TFAM	PPARGC1A	Q9UBK2	895
TFAM	GABPB1	Q06547	883
TFAM	GABPA	Q06546	845
TFAM	SIRT1	Q96EB6	811
TFAM	MFN2	O95140	804
TFAM	SSBP1	Q04837	802
TFAM	TOMM20	Q15388	796
TFAM	POLG	P54098	791
TFAM	MT-ATP8	P03928	781
TFAM	TWNK	Q96RR1	778
TFAM	MFN1	Q8IWA4	778

IntAct

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

17 partners by confidence:

Partner	Interaction type	MIscore	Records
MGST3	physical association	0.660	3
AGTRAP	physical association	0.560	6
ARL6IP1	physical association	0.560	3
COL8A2	physical association	0.560	3
STATH	physical association	0.560	3
TECR	physical association	0.560	3
TSPAN1	physical association	0.560	3
POLRMT	physical association	0.560	2
TFB1M	physical association	0.540	2
LONP1	protein cleavage	0.440	1
TFB2M	direct interaction	0.440	1
ACOT2	physical association	0.400	1
ERAL1	association	0.350	1
MRPS14	association	0.350	1
IKBKE	physical association	0.000	1
MCC	physical association	0.000	1
TNIK	physical association	0.000	1

BioGRID (519 interactions; top human partners by supporting records): C1QBP (Proximity Label-MS; 3 records), CLPP (Proximity Label-MS; 3 records), MYC (Affinity Capture-MS; 3 records), TCEA2 (Cross-Linking-MS (XL-MS); 3 records), TFB1M (Affinity Capture-Western; 3 records), ACE2 (Affinity Capture-MS; 2 records), ACOT2 (Proximity Label-MS; 2 records), AGTRAP (Two-hybrid; 2 records), ANLN (Affinity Capture-MS; 2 records), ARID4A (Cross-Linking-MS (XL-MS); 2 records), BRD4 (Affinity Capture-MS; 2 records), CDCA2 (Cross-Linking-MS (XL-MS); 2 records), CS (Proximity Label-MS; 2 records), DLG1 (Cross-Linking-MS (XL-MS); 2 records), EGFR (Negative Genetic; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
PRKACA	up-regulates	TFAM	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for TFAM: 107 ClinVar records (2 pathogenic / likely pathogenic); 6 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	41
Likely benign	36
Benign	20

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
221285	NM_003201.3(TFAM):c.533C>T (p.Pro178Leu)	Likely pathogenic	criteria provided, single submitter	2
2585248	NM_003201.3(TFAM):c.441del (p.Glu148fs)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore TFAM’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 23 predictions of 622):

Position(s)	Effect	Δscore	Sites
10:58385649–58385650	donor_loss	1.0000	4
10:58386215	acceptor_gain	1.0000
10:58388177	acceptor_gain	1.0000
10:58388182	acceptor_gain	1.0000
10:58388187	acceptor_gain	1.0000
10:58388188–58388189	acceptor_loss	1.0000	4
10:58388261–58388262	donor_loss	1.0000	4
10:58388668–58388669	acceptor_loss	1.0000	5
10:58388799	donor_gain	1.0000
10:58388820	donor_loss	1.0000

AlphaMissense

288 missense substitutions predicted likely pathogenic (of 1,607 scored), across 100 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
F60	7	0.980	0.997
W88	7	0.977	0.991
W218	7	0.970	0.992
W189	7	0.957	0.986
P155	6	0.939	0.974
M222	6	0.918	0.962
P53	6	0.871	0.961
K154	6	0.854	0.975
F170	6	0.845	0.944
E219	6	0.769	0.884
P50	6	0.699	0.790
D229	6	0.647	0.733
K96	5	0.917	0.976
Y57	5	0.905	0.966
K156	5	0.860	0.936
Y165	5	0.852	0.981
K52	5	0.827	0.900
Y211	5	0.822	0.959
K197	5	0.809	0.967
G153	5	0.784	0.929

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
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	7.9e-08
Glioblastoma Multiforme (validation)	favorable	6.12e-06
Colon Adenocarcinoma (validation)	favorable	0.000717

Disease associations

OMIM: gene MIM:600438 | disease phenotypes: MIM:617156

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
mitochondrial DNA depletion syndrome 15 (hepatocerebral type)	Strong	Autosomal recessive	3

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (9 panels, 8 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

9 panels:

Panel	Rating
Hypotonic infant	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Mitochondrial DNA maintenance disorder	green
Mitochondrial disorders	green
Paediatric disorders	green
Possible mitochondrial disorder, nuclear genes	green
Unexplained death in infancy and sudden unexplained death in childhood	green
Mitochondrial liver disease	amber

Mondo (1): mitochondrial DNA depletion syndrome 15 (hepatocerebral type) (MONDO:0014943)

HPO phenotypes

28 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000952	Jaundice
HP:0001254	Lethargy
HP:0001394	Cirrhosis
HP:0001396	Cholestasis
HP:0001399	Hepatic failure
HP:0001414	Microvesicular hepatic steatosis
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001522	Death in infancy
HP:0001541	Ascites
HP:0001561	Polyhydramnios
HP:0001635	Congestive heart failure
HP:0001943	Hypoglycemia
HP:0002098	Respiratory distress
HP:0002904	Hyperbilirubinemia
HP:0002908	Conjugated hyperbilirubinemia
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003073	Hypoalbuminemia
HP:0003155	Elevated circulating alkaline phosphatase concentration
HP:0003161	4-Hydroxyphenylpyruvic aciduria
HP:0003231	Hypertyrosinemia
HP:0003235	Hypermethioninemia
HP:0003270	Abdominal distention
HP:0003607	4-hydroxyphenylacetic aciduria
HP:0003623	Neonatal onset
HP:0003676	Progressive
HP:0009141	Depletion of mitochondrial DNA in muscle tissue

GWAS associations

6 associations:

Study	Trait	p-value
GCST011878_1	Mitochondrial heteroplasmy measurement	2e-223
GCST010002_90	Refractive error	2e-44
GCST005986_8	Blood urea nitrogen levels	2e-9
GCST004283_11	Midgestational circulating levels of PCBs	2e-6
GCST001885_10	Height	6e-6
GCST009391_40	Metabolite levels	8e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0007042	polychlorinated biphenyls measurement
EFO:0007964	gestational serum measurement
EFO:0010116	choline measurement
EFO:0600008	mitochondrial heteroplasmy measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067181 (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

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.31	Kd	48.7	nM	CHEMBL5653589
7.31	ED50	48.7	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 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	2149575: Binding affinity to human TFAM incubated for 45 mins by Kinobead based pull down assay	kd	0.0487	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Resveratrol	decreases reaction, increases expression, increases reaction, affects cotreatment, decreases expression	7
Rotenone	decreases expression, decreases reaction, affects cotreatment, increases expression	4
Arsenic	decreases methylation, increases expression	3
Doxorubicin	decreases expression, decreases reaction, increases expression, affects reaction	3
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	decreases expression, affects cotreatment, increases expression	2
Acetylcysteine	decreases reaction, decreases expression	2
Atrazine	decreases expression	2
Benzo(a)pyrene	decreases reaction, decreases expression	2
Dichlorodiphenyl Dichloroethylene	increases expression, increases activity	2
Glucose	affects cotreatment, decreases expression, decreases reaction, increases reaction, increases expression (+1 more)	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Palmitic Acid	affects cotreatment, decreases expression, decreases reaction, increases reaction, affects reaction	2
PQQ Cofactor	decreases expression, decreases reaction	2
afuresertib	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
SR18292	decreases expression, decreases reaction	1
3-monochloropropane-1, 2 diol ester	increases expression, decreases reaction, increases phosphorylation, increases secretion	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
oxybenzone	increases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
3,4-dihydroxyphenylethanol	decreases expression, decreases reaction	1
kaempferol	increases expression	1
bisphenol A	increases expression	1
cobaltiprotoporphyrin	decreases reaction, increases expression	1
di-n-octyl phthalate	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652617	Binding	Binding affinity to human TFAM incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Clinical trials (associated diseases)

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

showing 60 of 178 trials:

NCT	Phase	Status	Title
NCT00417066	Phase 4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	Phase 4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	Phase 4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	Phase 4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	Phase 4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	Phase 4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	Phase 3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT01655212	Phase 3	TERMINATED	Congenital Cytomegalovirus: Efficacy of Antiviral Treatment in a Randomized Controlled Trial
NCT02005822	Phase 3	COMPLETED	Congenital Cytomegalovirus: Efficacy of Antiviral Treatment
NCT03374514	Phase 3	UNKNOWN	Cochlear Electrical Impedance and the Effect of Topical Dexamethasone on Cochlear Implant Surgery
NCT00001951	Phase 2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	Phase 2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	Phase 2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	Phase 2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	Phase 2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	Phase 2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02497690	Phase 2	COMPLETED	Effectiveness of Therapy Via Telemedicine Following Cochlear Implants
NCT03107871	Phase 2	TERMINATED	Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants
NCT04120116	Phase 2	COMPLETED	FX-322 in Adults With Stable Sensorineural Hearing Loss
NCT05061758	Phase 2	WITHDRAWN	A Trial of LY3056480 in Patients With SNLH
NCT07364747	Phase 2	RECRUITING	Protective Effect of Acetylcysteine Against Cisplatinum-Induced Ototoxicity: A Randomized Controlled Trial
NCT02912104	Phase 1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	Phase 1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	Phase 1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	Phase 1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	Phase 1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT02038972	Phase 1	COMPLETED	Safety of Autologous Stem Cell Infusion for Children With Acquired Hearing Loss
NCT02259595	Phase 1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT00948857	Phase 2/3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	Phase 2/3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	Phase 1/2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	Phase 1/2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	Phase 1/2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	Phase 1/2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	Phase 1/2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	Phase 1/2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	Phase 1/2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	Phase 1/2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	Phase 1/2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	Phase 1/2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	Phase 1/2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	Phase 1/2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	Phase 1/2	COMPLETED	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	Early Phase 1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	Early Phase 1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	Early Phase 1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists
NCT00295087	Not specified	COMPLETED	X-Chromosome Inactivation Status and Premature Ovarian Failure
NCT00417157	Not specified	COMPLETED	Modified Natural Cycle Offers a Chance of Pregnancy in Patients With Poor Response and High Basal FSH
NCT00619333	Not specified	UNKNOWN	Inactive FSH in Galactosemia
NCT00780897	Not specified	UNKNOWN	Premature Ovarian Failure (Genetic and Physiopathologic Analysis)
NCT01187524	Not specified	TERMINATED	The Natural History of Reproductive and Overall Health in Girls and Women With a Pre-Mutation in the FMR1 Gene; Creation of a Patient Registry
NCT01411644	Not specified	UNKNOWN	Pheno- & Genotyping POF (WHO III)
NCT02086318	Not specified	UNKNOWN	A New Algorithm to Predict Ovarian Age
NCT02467231	Not specified	ACTIVE_NOT_RECRUITING	Ovarian Reserve After Cancer: Longitudinal Effects
NCT02696889	Not specified	COMPLETED	Rejuvenation of Premature Ovarian Failure With Stem Cells
NCT02779374	Not specified	TERMINATED	Autologous Bone Marrow Transplantation for Premature Ovarian Insufficiency

Predicted chemistry — Sugi Predict

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