LEF1
lymphoid enhancer binding factor 1, the group of TCF/LEF transcription factor family|Wnt enhanceosome complex
Basic information
Region (hg38): 4:108047545-108168956
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Ectrodactyly (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the LEF1 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 | |||||
| missense | 18 | 19 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 1 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 1 | |||||
| Total | 2 | 0 | 18 | 1 | 2 |
Variants in LEF1
This is a list of pathogenic ClinVar variants found in the LEF1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 4-108063660-G-C | not specified | Uncertain significance (Mar 25, 2024) | ||
| 4-108064359-T-C | not specified | Uncertain significance (Dec 27, 2023) | ||
| 4-108064378-T-A | Uncertain significance (Dec 22, 2023) | |||
| 4-108070731-CATA-C | Ectrodactyly | Pathogenic (Nov 01, 2021) | ||
| 4-108078276-C-T | not specified | Uncertain significance (May 31, 2022) | ||
| 4-108078300-T-C | Abnormal radial ray morphology | Uncertain significance (Nov 01, 2021) | ||
| 4-108078315-C-T | Uncertain significance (Jul 11, 2022) | |||
| 4-108078341-C-T | not specified | Uncertain significance (Jul 25, 2023) | ||
| 4-108079478-G-A | LEF1-related disorder | Likely benign (Feb 01, 2022) | ||
| 4-108079511-C-T | not specified | Uncertain significance (Dec 03, 2021) | ||
| 4-108079571-T-C | not specified | Uncertain significance (May 27, 2022) | ||
| 4-108079591-C-T | not specified | Uncertain significance (Nov 18, 2022) | ||
| 4-108079592-C-T | not specified | Uncertain significance (Dec 03, 2021) | ||
| 4-108083392-G-A | not specified | Uncertain significance (Apr 04, 2023) | ||
| 4-108083397-C-A | not specified | Uncertain significance (Mar 20, 2023) | ||
| 4-108083410-G-C | Uncertain significance (-) | |||
| 4-108083452-A-C | Benign (Jul 25, 2018) | |||
| 4-108089127-TG-T | Ectrodactyly | Pathogenic (Nov 01, 2021) | ||
| 4-108089142-T-A | not specified | Uncertain significance (Jul 14, 2022) | ||
| 4-108089239-C-A | not specified | Uncertain significance (Mar 19, 2024) | ||
| 4-108163569-G-A | not specified | Uncertain significance (May 14, 2024) | ||
| 4-108163608-T-C | not specified | Uncertain significance (Jul 13, 2021) | ||
| 4-108163639-T-G | not specified | Uncertain significance (Oct 12, 2022) | ||
| 4-108163655-C-T | Benign (Aug 14, 2018) | |||
| 4-108163677-T-C | not specified | Uncertain significance (Oct 31, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| LEF1 | protein_coding | protein_coding | ENST00000265165 | 11 | 121412 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.998 | 0.00211 | 125742 | 0 | 5 | 125747 | 0.0000199 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.57 | 167 | 235 | 0.711 | 0.0000119 | 2619 |
| Missense in Polyphen | 71 | 120.24 | 0.59047 | 1386 | ||
| Synonymous | 0.282 | 86 | 89.4 | 0.962 | 0.00000521 | 750 |
| Loss of Function | 4.19 | 1 | 22.4 | 0.0446 | 9.49e-7 | 277 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000264 | 0.0000264 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Participates in the Wnt signaling pathway. Activates transcription of target genes in the presence of CTNNB1 and EP300. May play a role in hair cell differentiation and follicle morphogenesis. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by LEF1 and CTNNB1. Regulates T-cell receptor alpha enhancer function. Binds DNA in a sequence-specific manner. PIAG antagonizes both Wnt-dependent and Wnt-independent activation by LEF1 (By similarity). Isoform 3 lacks the CTNNB1 interaction domain and may be an antagonist for Wnt signaling. Isoform 5 transcriptionally activates the fibronectin promoter, binds to and represses transcription from the E-cadherin promoter in a CTNNB1- independent manner, and is involved in reducing cellular aggregation and increasing cell migration of pancreatic cancer cells. Isoform 1 transcriptionally activates MYC and CCND1 expression and enhances proliferation of pancreatic tumor cells. {ECO:0000250, ECO:0000269|PubMed:11266540, ECO:0000269|PubMed:19653274, ECO:0000269|PubMed:2010090}.;
- 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);WNT-Core;Arrhythmogenic Right Ventricular Cardiomyopathy;Hair Follicle Development- Induction (Part 1 of 3);Endoderm Differentiation;Mesodermal Commitment Pathway;Wnt Signaling Pathway;Hepatitis C and Hepatocellular Carcinoma;Wnt-beta-catenin Signaling Pathway in Leukemia;Regulation of Wnt-B-catenin Signaling by Small Molecule Compounds;Amplification and Expansion of Oncogenic Pathways as Metastatic Traits;Canonical and Non-canonical Notch signaling;Wnt Signaling Pathway and Pluripotency;Endometrial cancer;Chromosomal and microsatellite instability in colorectal cancer;Wnt Signaling Pathway;TGF-beta Receptor Signaling;DNA Damage Response (only ATM dependent);Degradation of beta-catenin by the destruction complex;Notch;Signaling by WNT;Signal Transduction;Gene expression (Transcription);RUNX3 regulates WNT signaling;Transcriptional regulation by RUNX3;multi-step regulation of transcription by pitx2;Generic Transcription Pathway;Repression of WNT target genes;RNA Polymerase II Transcription;inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages;Deactivation of the beta-catenin transactivating complex;TGF_beta_Receptor;Ca2+ pathway;Beta-catenin independent WNT signaling;C-MYB transcription factor network;Wnt;Wnt Canonical;Regulation of nuclear beta catenin signaling and target gene transcription;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
- 0.832
Intolerance Scores
- loftool
- 0.0162
- rvis_EVS
- 0.2
- rvis_percentile_EVS
- 67.19
Haploinsufficiency Scores
- pHI
- 0.927
- hipred
- Y
- hipred_score
- 0.827
- ghis
- 0.496
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.988
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Lef1
- Phenotype
- cellular phenotype; craniofacial 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; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; immune system phenotype; skeleton 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; vision/eye 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); reproductive system 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); hematopoietic system phenotype; pigmentation phenotype; embryo phenotype;
Zebrafish Information Network
- Gene name
- lef1
- Affected structure
- melanocyte
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;branching involved in blood vessel morphogenesis;osteoblast differentiation;somitogenesis;epithelial to mesenchymal transition;sprouting angiogenesis;regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;Wnt signaling pathway, calcium modulating pathway;positive regulation of cell population proliferation;positive regulation of gene expression;positive regulation of epithelial to mesenchymal transition;dentate gyrus development;forebrain radial glial cell differentiation;forebrain neuroblast division;formation of radial glial scaffolds;regulation of cell-cell adhesion;regulation of Wnt signaling pathway;neutrophil differentiation;positive regulation of cell growth;embryonic limb morphogenesis;positive regulation of cell migration;BMP signaling pathway;positive regulation of granulocyte differentiation;mammary gland development;negative regulation of interleukin-13 production;negative regulation of interleukin-4 production;negative regulation of interleukin-5 production;T cell receptor V(D)J recombination;B cell proliferation;odontogenesis of dentin-containing tooth;negative regulation of apoptotic process;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;negative regulation of DNA binding;steroid hormone mediated signaling pathway;tongue development;positive regulation by host of viral transcription;histone H3 acetylation;histone H4 acetylation;T-helper 1 cell differentiation;negative regulation of striated muscle tissue development;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;alpha-beta T cell differentiation;eye pigmentation;paraxial mesoderm formation;sensory perception of taste;anatomical structure regression;canonical Wnt signaling pathway;face morphogenesis;cell chemotaxis;apoptotic process involved in morphogenesis;chorio-allantoic fusion;trachea gland development;secondary palate development;cellular response to cytokine stimulus;cellular response to interleukin-4;positive regulation of cell proliferation in bone marrow;negative regulation of apoptotic process in bone marrow cell;odontoblast differentiation;negative regulation of estrogen receptor binding;apoptotic process involved in blood vessel morphogenesis;beta-catenin-TCF complex assembly
- Cellular component
- nucleus;nucleoplasm;transcription factor complex;cytoplasm;protein-DNA complex;beta-catenin-TCF complex
- Molecular function
- RNA polymerase II regulatory region sequence-specific DNA binding;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;chromatin binding;DNA-binding transcription factor activity;protein binding;beta-catenin binding;DNA binding, bending;estrogen receptor activity;estrogen receptor binding;enhancer binding;histone binding;histone deacetylase binding;cysteine-type endopeptidase inhibitor activity involved in apoptotic process;sequence-specific DNA binding;transcription regulatory region DNA binding;gamma-catenin binding;armadillo repeat domain binding;C2H2 zinc finger domain binding