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.

not_specified (22 variants)
not_provided (2 variants)

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. These statistics are base on transcript: NM_001271944.2. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense			22 clinvar	1 clinvar		23
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	22	1	1

Loading clinvar variants...

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