TFE3

transcription factor binding to IGHM enhancer 3, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): X:49028726-49043410

Links

ENSG00000068323 ∙ NCBI:7030 ∙ OMIM:314310 ∙ HGNC:11752 ∙ Uniprot:P19532 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Moderate), mode of inheritance: AD
• intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies (Strong), mode of inheritance: XL
• syndromic complex neurodevelopmental disorder (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies	XL	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	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	30595499; 31833172

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TFE3 gene.

• Intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies (3 variants)
• not provided (2 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TFE3 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				5		5
missense	4	7	34	8	1	54
nonsense						0
start loss						0
frameshift			1			1
inframe indel		1	2		1	4
splice donor/acceptor (+/-2bp)			1			1
splice region			1			1
non coding			1	3		4
Total	4	8	39	16	2

Variants in TFE3

This is a list of pathogenic ClinVar variants found in the TFE3 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-49030168-T-C			Uncertain significance (Oct 19, 2023)
X-49030170-T-C			Likely benign (Jul 03, 2018)
X-49030171-T-C		Inborn genetic diseases	Uncertain significance (Apr 18, 2023)
X-49030187-T-G			Uncertain significance (May 16, 2022)
X-49030190-G-T			Uncertain significance (Dec 13, 2023)
X-49030192-C-T		Renal cell carcinoma, Xp11-associated	Uncertain significance (Nov 30, 2021)
X-49030252-C-T		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
X-49030294-C-T			Likely benign (Dec 01, 2022)
X-49030294-CCCT-C		Inborn genetic diseases	Benign (Oct 19, 2022)
X-49030297-T-A		TFE3-related disorder	Uncertain significance (Dec 22, 2023)
X-49030361-G-T		not specified	Uncertain significance (May 04, 2022)
X-49030431-C-A		TFE3-related disorder	Uncertain significance (Jul 10, 2021)
X-49030435-G-A		Inborn genetic diseases	Likely benign (Nov 08, 2021)
X-49030436-C-T			Benign (Jul 23, 2018)
X-49030440-TC-T			Uncertain significance (Jun 09, 2022)
X-49030444-C-A		Inborn genetic diseases	Likely benign (Mar 23, 2023)
X-49030447-C-A			Likely benign (Jul 10, 2018)
X-49030447-C-G			Likely benign (Jun 01, 2018)
X-49030447-C-T		Inborn genetic diseases	Likely benign (Jun 30, 2023)
X-49030466-C-T		Inborn genetic diseases	Likely benign (Jun 06, 2023)
X-49030478-C-T		Inborn genetic diseases	Likely benign (Sep 06, 2022)
X-49030513-C-T		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
X-49030524-C-T			Likely benign (Dec 01, 2022)
X-49030532-T-C			Uncertain significance (Mar 02, 2022)
X-49030563-T-C		TFE3-related disorder	Benign (Aug 15, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TFE3	protein_coding	protein_coding	ENST00000315869	10	14771

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.980	0.0201	125660	2	1	125663	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.15	140	232	0.602	0.0000197	3639
Missense in Polyphen		14	19.607	0.71401		262
Synonymous	0.830	92	103	0.896	0.00000879	1266
Loss of Function	3.52	1	16.3	0.0612	0.00000131	262

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000934	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000765	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000124	0.00000880
Middle Eastern	0.0000765	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

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 TFEB or MITF. In association with TFEB, 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 the MUE3 box, a subset of E-boxes, present in the immunoglobulin enhancer. It also binds very well to a USF/MLTF site.
• Disease: DISEASE: Note=A chromosomal aberration involving TFE3 is found in patients with alveolar soft part sarcoma. Translocation t(X;17)(p11;q25) with ASPSCR1 forms a ASPSCR1-TFE3 fusion protein. {ECO:0000269|PubMed:11358836}.; DISEASE: Note=Chromosomal aberrations involving TFE3 are found in patients with papillary renal cell carcinoma. Translocation t(X;1)(p11.2;q21.2) with PRCC; translocation t(X;1)(p11.2;p34) with PSF; inversion inv(X)(p11.2;q12) that fuses NONO to TFE3. {ECO:0000269|PubMed:8872474, ECO:0000269|PubMed:8986805}.
• Pathway: Renal cell carcinoma - Homo sapiens (human);Mitophagy - animal - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Type 2 papillary renal cell carcinoma;TGF-beta Receptor Signaling;Regulation of nuclear SMAD2/3 signaling;E2F transcription factor network (Consensus)

Recessive Scores

• pRec: 0.242

Intolerance Scores

• loftool: 0.192
• rvis_EVS: 0.51
• rvis_percentile_EVS: 80.01

Haploinsufficiency Scores

• pHI: 0.603
• hipred: Y
• hipred_score: 0.775
• ghis: 0.519

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.170

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tfe3
• Phenotype: vision/eye phenotype; immune system phenotype; skeleton phenotype; hematopoietic system 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); normal phenotype; pigmentation phenotype; craniofacial 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)

Gene ontology

• Biological process: adaptive immune response;humoral immune response;regulation of osteoclast differentiation;positive regulation of cell adhesion;positive regulation of transcription by RNA polymerase II;negative regulation of cold-induced thermogenesis
• Cellular component: nucleus;nucleoplasm;cytosol
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;transcription regulatory region DNA binding;protein dimerization activity