TFEB

transcription factor EB, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 6:41683978-41736259

Links

ENSG00000112561 ∙ NCBI:7942 ∙ OMIM:600744 ∙ HGNC:11753 ∙ Uniprot:P19484 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TFEB 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					1	1
missense			17	1		18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	17	1	1

Variants in TFEB

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

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

Position	Type	Phenotype	Significance	ClinVar
6-41684636-C-T		not specified	Uncertain significance (Oct 12, 2024)
6-41684663-G-A			Uncertain significance (Jun 04, 2021)
6-41684867-G-A		not specified	Uncertain significance (Dec 10, 2024)
6-41684868-G-A		not specified	Uncertain significance (Aug 17, 2021)
6-41684891-G-A		not specified	Uncertain significance (Nov 10, 2021)
6-41684916-G-T		not specified	Uncertain significance (Dec 20, 2023)
6-41685024-T-C		not specified	Likely benign (Dec 14, 2023)
6-41686133-C-T		not specified	Uncertain significance (Dec 12, 2023)
6-41686140-G-T		not specified	Uncertain significance (Nov 10, 2023)
6-41686233-C-T		not specified	Uncertain significance (Nov 03, 2023)
6-41687104-C-T		not specified	Uncertain significance (Jan 16, 2024)
6-41687779-C-T		not specified	Uncertain significance (Nov 18, 2022)
6-41687987-G-T		not specified	Uncertain significance (Jul 31, 2024)
6-41690712-G-A		not specified	Uncertain significance (Jun 09, 2022)
6-41690745-T-C		not specified	Uncertain significance (Nov 09, 2024)
6-41690800-C-T		not specified	Uncertain significance (Jun 13, 2024)
6-41691046-G-A			Benign (Jul 07, 2018)
6-41691063-G-A		not specified	Uncertain significance (Feb 02, 2024)
6-41691114-T-A		not specified	Uncertain significance (Jul 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TFEB	protein_coding	protein_coding	ENST00000230323	8	52282

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.899	0.101	125692	0	10	125702	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.77	192	274	0.699	0.0000164	3082
Missense in Polyphen		58	103.77	0.55895		1198
Synonymous	0.560	110	118	0.934	0.00000749	943
Loss of Function	3.60	3	20.6	0.145	0.00000115	210

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000145	0.000145
Ashkenazi Jewish	0.000341	0.000298
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000111	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor that specifically recognizes and binds E-box sequences (5'-CANNTG-3'). Efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFE3 or MITF. In association with TFE3, activates the expression of CD40L in T-cells, thereby playing a role in T- cell-dependent antibody responses in activated CD4(+) T-cells and thymus-dependent humoral immunity. Specifically recognizes and binds the CLEAR-box sequence (5'-GTCACGTGAC-3') present in the regulatory region of many lysosomal genes, leading to activate their expression. It thereby plays a central role in expression of lysosomal genes. Acts as a positive regulator of autophagy by promoting expression of genes involved in autophagy. Specifically recognizes the gamma-E3 box, a subset of E-boxes, present in the heavy-chain immunoglobulin enhancer. Plays a role in the signal transduction processes required for normal vascularization of the placenta. {ECO:0000269|PubMed:19556463, ECO:0000269|PubMed:23434374}.
• Pathway: Mitophagy - animal - Homo sapiens (human);PI3K-AKT-mTOR signaling pathway and therapeutic opportunities;Type 2 papillary renal cell carcinoma (Consensus)

Recessive Scores

• pRec: 0.172

Intolerance Scores

• loftool: 0.0717
• rvis_EVS: -0.6
• rvis_percentile_EVS: 17.91

Haploinsufficiency Scores

• pHI: 0.308
• hipred: Y
• hipred_score: 0.662
• ghis: 0.574

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.179

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tfeb
• Phenotype: normal phenotype; 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); pigmentation phenotype; embryo phenotype; skeleton phenotype; vision/eye 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); growth/size/body region phenotype

Gene ontology

• Biological process: embryonic placenta development;adaptive immune response;regulation of transcription, DNA-templated;autophagy;humoral immune response;lysosome organization;positive regulation of autophagy;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus;cytoplasm
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;transcription regulatory region DNA binding;protein dimerization activity