TLE6

TLE family member 6, subcortical maternal complex member, the group of TLE family|Subcortical maternal complex|WD repeat domain containing

Basic information

Region (hg38): 19:2977538-2995179

Links

ENSG00000104953 ∙ NCBI:79816 ∙ OMIM:612399 ∙ HGNC:30788 ∙ Uniprot:Q9H808 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• preimplantation embryonic lethality 1 (Limited), mode of inheritance: AR
• preimplantation embryonic lethality 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Oocyte/zygote/embryo maturation arrest 15	AR	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	Obstetric	26537248

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TLE6 gene.

• Preimplantation embryonic lethality 1 (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TLE6 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				10	8	18
missense	1		41	7	1	50
nonsense						0
start loss						0
frameshift	2					2
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				4	2	6
non coding			2			2
Total	3	1	43	17	9

Highest pathogenic variant AF is 0.0000263

Variants in TLE6

This is a list of pathogenic ClinVar variants found in the TLE6 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-2978251-G-T		TLE6-related disorder	Benign (Jul 12, 2019)
19-2978271-C-T		not specified	Likely benign (Mar 15, 2024)
19-2981572-A-G		not specified	Uncertain significance (May 20, 2024)
19-2982152-A-G		not specified	Uncertain significance (Dec 22, 2023)
19-2982178-C-A		not specified	Uncertain significance (Feb 05, 2024)
19-2987014-C-T		not specified	Uncertain significance (Jun 06, 2023)
19-2987046-G-A		Preimplantation embryonic lethality 1	Uncertain significance (Mar 09, 2023)
19-2987050-C-T		not specified	Uncertain significance (Jan 19, 2024)
19-2987055-T-C			Likely benign (Dec 31, 2019)
19-2987079-T-C		not specified	Uncertain significance (Feb 22, 2023)
19-2987083-C-A		not specified	Uncertain significance (Mar 29, 2023)
19-2987097-C-T		not specified	Uncertain significance (Jun 06, 2023)
19-2987106-G-C		not specified	Uncertain significance (Oct 17, 2023)
19-2987107-G-A		not specified	Likely benign (Aug 03, 2022)
19-2987116-A-G		not specified	Uncertain significance (Jan 19, 2022)
19-2987166-G-A		not specified	Uncertain significance (Jan 10, 2023)
19-2987216-G-C		not specified	Uncertain significance (Feb 22, 2023)
19-2987750-C-T			Likely benign (Nov 01, 2022)
19-2987757-C-T		not specified	Uncertain significance (Aug 13, 2021)
19-2987900-C-T			Uncertain significance (Feb 01, 2023)
19-2987906-C-A		not specified	Uncertain significance (Dec 03, 2021)
19-2987934-A-AG			Pathogenic (Jul 05, 2022)
19-2987971-C-T			Likely benign (Apr 16, 2018)
19-2988113-G-A		not specified	Uncertain significance (Feb 22, 2023)
19-2989060-G-C			Likely pathogenic (Jul 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TLE6	protein_coding	protein_coding	ENST00000246112	16	17734

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000302	0.999	125684	0	63	125747	0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0623	337	340	0.990	0.0000203	3730
Missense in Polyphen		87	98.908	0.8796		1105
Synonymous	-2.44	177	140	1.26	0.00000922	1082
Loss of Function	2.99	15	33.7	0.445	0.00000159	356

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000677	0.000677
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000301	0.000299
Middle Eastern	0.00	0.00
South Asian	0.000524	0.000523
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: As a member of the subcortical maternal complex (SCMC), plays an essential role for zygotes to progress beyond the first embryonic cell divisions. {ECO:0000269|PubMed:26537248}.
• Disease: DISEASE: Preimplantation embryonic lethality 1 (PREMBL1) [MIM:616814]: A rare cause of female primary infertility. In affected women, ovulation proceeds normally and the retrieved oocytes appear normal, but zygote formation and division are severely impaired. Inheritance is autosomal recessive. {ECO:0000269|PubMed:26537248}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0950

Intolerance Scores

• loftool: 0.843
• rvis_EVS: -1.44
• rvis_percentile_EVS: 3.97

Haploinsufficiency Scores

• pHI: 0.0886
• hipred: N
• hipred_score: 0.251
• ghis: 0.645

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.111

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tle6

Gene ontology

• Biological process: regulation of transcription, DNA-templated;embryonic process involved in female pregnancy;negative regulation of canonical Wnt signaling pathway;negative regulation of nucleic acid-templated transcription
• Cellular component: nucleus;transcription factor complex;cytoplasm;protein-containing complex
• Molecular function: transcription corepressor activity;protein binding;repressing transcription factor binding