TLL1

tolloid like 1, the group of Astacins

Basic information

Region (hg38): 4:165873236-166104457

Links

ENSG00000038295 ∙ NCBI:7092 ∙ OMIM:606742 ∙ HGNC:11843 ∙ Uniprot:O43897 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• atrial septal defect 6 (Limited), mode of inheritance: AD
• atrial septal defect 6 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Atrial septal defect 6	AD	Cardiovascular	In addition to managing congenital cardiac malformations, surveillance for (eg, including electrocardiogram) and treatment of accompanying arrhythmias may be effective	Cardiovascular	18830233
The condition can include arrhthymias as well as frank congenital cardiac malformations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TLL1 gene.

• Inborn genetic diseases (40 variants)
• not provided (38 variants)
• Atrial septal defect 6 (13 variants)
• TLL1-related condition (5 variants)
• not specified (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TLL1 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		4	5
missense			52	2	1	55
nonsense			3			3
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region			1	1	1	3
non coding					26	26
Total	1	0	56	2	31

Variants in TLL1

This is a list of pathogenic ClinVar variants found in the TLL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-165873677-T-C			Benign (Nov 12, 2018)
4-165873918-C-A		not specified	Likely benign (Apr 08, 2022)
4-165873949-G-T			Benign (May 01, 2022)
4-165873966-T-C		not specified	Uncertain significance (Dec 21, 2023)
4-165873971-G-C		TLL1-related disorder	Benign (Nov 26, 2019)
4-165873987-G-C		not specified	Uncertain significance (Jan 10, 2023)
4-165873989-G-A		not specified	Uncertain significance (Sep 06, 2023)
4-165873997-C-A			Benign (Dec 31, 2019)
4-165989373-T-C		TLL1-related disorder	Likely benign (Jul 30, 2019)
4-165989462-A-T		not specified	Uncertain significance (Oct 26, 2022)
4-165989480-G-A		not specified	Uncertain significance (Jul 30, 2023)
4-165992843-C-T		not specified	Uncertain significance (May 06, 2022)
4-165994431-G-A		TLL1-related disorder	Uncertain significance (May 23, 2023)
4-165994456-C-T		not specified	Uncertain significance (Dec 15, 2023)
4-165994503-A-G		not specified	Uncertain significance (Apr 07, 2023)
4-165994701-G-A			Benign (Nov 12, 2018)
4-165995070-G-C		not specified	Uncertain significance (Sep 06, 2022)
4-165995090-A-C		Atrial septal defect 6	Pathogenic (Mar 01, 2009)
4-165995090-A-G		not specified	Uncertain significance (Nov 10, 2022)
4-165995119-G-A		TLL1-related disorder	Likely benign (Aug 28, 2019)
4-165995154-T-C		not specified	Uncertain significance (Aug 17, 2021)
4-165995175-G-A		Atrial septal defect 6	Uncertain significance (Mar 25, 2024)
4-166003420-A-G			Likely benign (Mar 01, 2023)
4-166003471-T-C		Atrial septal defect 6	Uncertain significance (Nov 01, 2023)
4-166003554-G-C		not specified	Uncertain significance (Jun 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TLL1	protein_coding	protein_coding	ENST00000061240	21	230638

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.173	0.827	125725	0	23	125748	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.940	484	546	0.887	0.0000289	6687
Missense in Polyphen		112	171.67	0.65242		2115
Synonymous	-0.942	208	191	1.09	0.0000103	1818
Loss of Function	5.44	14	59.1	0.237	0.00000347	685

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000971	0.0000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000982	0.0000980
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Protease which processes procollagen C-propeptides, such as chordin, pro-biglycan and pro-lysyl oxidase. Required for the embryonic development. Predominant protease, which in the development, influences dorsal-ventral patterning and skeletogenesis.
• Disease: DISEASE: Atrial septal defect 6 (ASD6) [MIM:613087]: A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria. {ECO:0000269|PubMed:18830233}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Crosslinking of collagen fibrils;Assembly of collagen fibrils and other multimeric structures;Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization;DroToll-like;Anchoring fibril formation;Degradation of the extracellular matrix (Consensus)

Recessive Scores

• pRec: 0.137

Intolerance Scores

• loftool: 0.461
• rvis_EVS: -0.93
• rvis_percentile_EVS: 9.72

Haploinsufficiency Scores

• pHI: 0.547
• hipred: Y
• hipred_score: 0.704
• ghis: 0.572

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.397

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tll1
• Phenotype: limbs/digits/tail phenotype; digestive/alimentary phenotype; skeleton phenotype; immune system phenotype; liver/biliary system 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); 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); 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; growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: tll1
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: bifurcated

Gene ontology

• Biological process: skeletal system development;proteolysis;extracellular matrix disassembly;cell differentiation
• Cellular component: extracellular region
• Molecular function: metalloendopeptidase activity;serine-type endopeptidase activity;calcium ion binding;zinc ion binding