TCF7L1

transcription factor 7 like 1, the group of Wnt enhanceosome complex|TCF/LEF transcription factor family

Basic information

Region (hg38): 2:85133392-85310387

Previous symbols: [ "TCF3" ]

Links

ENSG00000152284 ∙ NCBI:83439 ∙ OMIM:604652 ∙ HGNC:11640 ∙ Uniprot:Q9HCS4 ∙ 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 TCF7L1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TCF7L1 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			34	2	1	37
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					9	9
Total	0	0	34	3	10

Variants in TCF7L1

This is a list of pathogenic ClinVar variants found in the TCF7L1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-85133689-C-A		not specified	Uncertain significance (Jun 21, 2022)
2-85133691-C-A		not specified	Uncertain significance (Oct 27, 2023)
2-85133705-GGGC-G			Likely benign (-)
2-85133718-G-A			Likely benign (Feb 01, 2023)
2-85133727-A-G		not specified	Uncertain significance (Dec 19, 2022)
2-85133734-G-A		not specified	Uncertain significance (Nov 17, 2023)
2-85133748-A-G		not specified	Likely benign (Apr 07, 2023)
2-85133793-G-A		not specified	Uncertain significance (May 05, 2023)
2-85133826-G-C		not specified	Uncertain significance (Oct 20, 2023)
2-85133847-A-G		not specified	Uncertain significance (Jun 16, 2023)
2-85133874-G-A		not specified	Uncertain significance (Jun 13, 2022)
2-85134023-G-C		not specified	Uncertain significance (Oct 27, 2022)
2-85134331-C-T		not specified	Uncertain significance (Mar 13, 2023)
2-85134367-C-T		not specified	Uncertain significance (Dec 21, 2022)
2-85283271-C-CCCG			Benign (Nov 12, 2018)
2-85283277-A-G			Benign (Nov 12, 2018)
2-85283302-G-A			Benign (Nov 12, 2018)
2-85283523-A-C		not specified	Uncertain significance (Oct 26, 2022)
2-85283531-T-A			Benign (Aug 09, 2018)
2-85283551-C-G		not specified	Uncertain significance (Jun 24, 2022)
2-85283552-A-C		not specified	Uncertain significance (Mar 08, 2024)
2-85283553-C-T		not specified	Uncertain significance (Jan 30, 2024)
2-85283565-C-G		not specified	Uncertain significance (May 26, 2023)
2-85283654-A-G			Benign (Nov 12, 2018)
2-85283842-A-G			Benign (Nov 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TCF7L1	protein_coding	protein_coding	ENST00000282111	12	176979

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.360	0.640	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.19	267	328	0.815	0.0000183	3746
Missense in Polyphen		100	146.11	0.6844		1659
Synonymous	-0.0998	147	145	1.01	0.00000886	1247
Loss of Function	3.69	6	26.5	0.227	0.00000121	305

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000120
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000445	0.0000439
Middle Eastern	0.000109	0.000109
South Asian	0.0000660	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Participates in the Wnt signaling pathway. Binds to DNA and acts as a repressor in the absence of CTNNB1, and as an activator in its presence. Necessary for the terminal differentiation of epidermal cells, the formation of keratohyalin granules and the development of the barrier function of the epidermis (By similarity). Down-regulates NQO1, leading to increased mitomycin c resistance. {ECO:0000250}.
• Pathway: Gastric cancer - Homo sapiens (human);Adherens junction - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);Breast cancer - Homo sapiens (human);Basal cell carcinoma - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Thyroid cancer - Homo sapiens (human);Endometrial cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Neural Crest Differentiation;Arrhythmogenic Right Ventricular Cardiomyopathy;White fat cell differentiation;Mesodermal Commitment Pathway;Ectoderm Differentiation;Preimplantation Embryo;Amplification and Expansion of Oncogenic Pathways as Metastatic Traits;Wnt Signaling Pathway and Pluripotency;White fat cell differentiation;Endometrial cancer;Chromosomal and microsatellite instability in colorectal cancer;Wnt Signaling Pathway;DNA Damage Response (only ATM dependent);Degradation of beta-catenin by the destruction complex;Signaling by WNT;Signal Transduction;Gene expression (Transcription);RUNX3 regulates WNT signaling;Transcriptional regulation by RUNX3;Generic Transcription Pathway;Repression of WNT target genes;RNA Polymerase II Transcription;Deactivation of the beta-catenin transactivating complex;Ca2+ pathway;Beta-catenin independent WNT signaling;Wnt Canonical;Regulation of nuclear beta catenin signaling and target gene transcription;Validated transcriptional targets of deltaNp63 isoforms;Binding of TCF/LEF:CTNNB1 to target gene promoters;Formation of the beta-catenin:TCF transactivating complex;TCF dependent signaling in response to WNT;Wnt Mammals (Consensus)

Recessive Scores

• pRec: 0.178

Intolerance Scores

• loftool: 0.118
• rvis_EVS: 0.0000761
• rvis_percentile_EVS: 53.98

Haploinsufficiency Scores

• pHI: 0.761
• hipred: Y
• hipred_score: 0.775
• ghis: 0.534

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.878

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tcf7l1
• 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); homeostasis/metabolism phenotype; cellular phenotype; embryo phenotype; 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); normal phenotype; vision/eye phenotype; 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); limbs/digits/tail phenotype

Zebrafish Information Network

• Gene name: tcf7l1b
• Affected structure: radial glial cell
• Phenotype tag: abnormal
• Phenotype quality: irregular spatial pattern

Gene ontology

• Biological process: chromatin organization;regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;regulation of Wnt signaling pathway;canonical Wnt signaling pathway;beta-catenin-TCF complex assembly
• Cellular component: nucleus;nucleoplasm;transcription factor complex;cytosol
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;chromatin binding;DNA-binding transcription factor activity;beta-catenin binding;sequence-specific DNA binding;transcription regulatory region DNA binding