TFAM

transcription factor A, mitochondrial

Basic information

Region (hg38): 10:58385344-58399220

Previous symbols: [ "TCF6", "TCF6L2" ]

Links

ENSG00000108064 ∙ NCBI:7019 ∙ OMIM:600438 ∙ HGNC:11741 ∙ Uniprot:Q00059 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial DNA depletion syndrome 15 (hepatocerebral type) (Limited), mode of inheritance: AR
• mitochondrial DNA depletion syndrome 15 (hepatocerebral type) (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial DNA depletion syndrome 15 (hepatocerebral type)	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Gastrointestinal; Musculoskeletal; Neurologic	27448789

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TFAM gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TFAM gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				8	1	9
missense		1	19	3	1	24
nonsense			1			1
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	2	1	5
non coding				15	13	28
Total	0	2	20	26	15

Variants in TFAM

This is a list of pathogenic ClinVar variants found in the TFAM region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-58385457-C-A			Likely benign (Aug 12, 2022)
10-58385498-A-G			Likely benign (Jul 03, 2018)
10-58385557-C-G		not specified	Uncertain significance (Jan 09, 2024)
10-58385575-G-T			Uncertain significance (Jun 15, 2023)
10-58385582-G-C		TFAM-related disorder	Benign (Jan 29, 2024)
10-58385596-T-C			Uncertain significance (Feb 17, 2022)
10-58385661-G-C			Likely benign (Jul 26, 2022)
10-58385837-G-C			Benign (Jun 14, 2018)
10-58386014-A-G			Likely benign (Jul 07, 2018)
10-58386035-T-A			Benign (Jun 26, 2018)
10-58386055-C-T			Likely benign (Jul 07, 2018)
10-58386082-GTC-G			Benign (Dec 09, 2018)
10-58386213-T-A			Likely benign (Mar 09, 2023)
10-58386214-A-G		TFAM-related disorder	Likely benign (Jul 16, 2023)
10-58386257-G-A		not specified	Uncertain significance (Jun 30, 2022)
10-58386301-T-C			Benign (Jan 26, 2024)
10-58386303-A-C			Uncertain significance (Feb 13, 2023)
10-58386304-A-G		TFAM-related disorder	Likely benign (Feb 18, 2019)
10-58388016-A-G			Likely benign (Jun 26, 2018)
10-58388024-G-A			Benign (Jun 14, 2018)
10-58388174-T-C			Benign (Jan 22, 2024)
10-58388187-T-C			Uncertain significance (Oct 05, 2023)
10-58388247-A-G		not specified	Uncertain significance (Sep 26, 2022)
10-58388249-T-G			Uncertain significance (Oct 05, 2023)
10-58388269-A-G		Mitochondrial DNA depletion syndrome 15 (hepatocerebral type) • TFAM-related disorder	Conflicting classifications of pathogenicity (Jun 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TFAM	protein_coding	protein_coding	ENST00000487519	7	14200

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.173	0.825	125736	0	7	125743	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.11	96	132	0.728	0.00000707	1585
Missense in Polyphen		14	36.589	0.38262		401
Synonymous	-0.371	46	42.9	1.07	0.00000223	438
Loss of Function	2.63	4	15.0	0.267	6.85e-7	185

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to the mitochondrial light strand promoter and functions in mitochondrial transcription regulation (PubMed:29445193). 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. {ECO:0000269|PubMed:1737790, ECO:0000269|PubMed:19304746, ECO:0000269|PubMed:20410300, ECO:0000269|PubMed:22037171, ECO:0000269|PubMed:22037172, ECO:0000269|PubMed:22841477, ECO:0000269|PubMed:29445193}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:27448789}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Huntington,s disease - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Energy Metabolism;Mitochondrial biogenesis;NAD metabolism, sirtuins and aging;Mitochondrial Gene Expression;Gene expression (Transcription);Transcriptional activation of mitochondrial biogenesis;Mitochondrial biogenesis;Mitochondrial transcription initiation;Transcription from mitochondrial promoters;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.202

Intolerance Scores

• loftool: 0.492
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.4

Haploinsufficiency Scores

• pHI: 0.0868
• hipred: N
• hipred_score: 0.432
• ghis: 0.577

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tfam
• Phenotype: embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: mitochondrial transcription;transcription initiation from mitochondrial promoter;mitochondrion organization;mitochondrial respiratory chain complex assembly;positive regulation of transcription, DNA-templated
• Cellular component: nucleus;mitochondrion;mitochondrial matrix;cytosol;protein-containing complex;mitochondrial nucleoid
• Molecular function: mitochondrial promoter sequence-specific DNA binding;transcription coactivator binding;chromatin binding;DNA-binding transcription factor activity;RNA binding;protein binding;DNA binding, bending;heat shock protein binding;sequence-specific DNA binding