TOLLIP

toll interacting protein, the group of C2 domain containing

Basic information

Region (hg38): 11:1274370-1309654

Links

ENSG00000078902 ∙ NCBI:54472 ∙ OMIM:606277 ∙ HGNC:16476 ∙ Uniprot:Q9H0E2 ∙ 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 TOLLIP gene.

• Inborn genetic diseases (16 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TOLLIP 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						0
missense			16		1	17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	16	0	1

Variants in TOLLIP

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

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

Position	Type	Phenotype	Significance	ClinVar
11-1277074-T-C			Benign (May 31, 2018)
11-1277077-C-T		not specified	Uncertain significance (Aug 13, 2021)
11-1277085-T-C		not specified	Likely benign (Dec 21, 2023)
11-1277153-G-C		not specified	Uncertain significance (Jul 27, 2021)
11-1277191-C-A		not specified	Uncertain significance (Jan 26, 2022)
11-1277197-C-T		not specified	Uncertain significance (Jul 19, 2023)
11-1286023-C-T		not specified	Uncertain significance (Oct 12, 2022)
11-1286056-C-T		not specified	Uncertain significance (Aug 13, 2021)
11-1286077-T-C		not specified	Uncertain significance (Jun 06, 2023)
11-1288638-C-T		not specified	Uncertain significance (Feb 21, 2024)
11-1288694-T-C		not specified	Uncertain significance (Feb 15, 2023)
11-1288703-A-T		not specified	Uncertain significance (Mar 07, 2024)
11-1288704-C-T		not specified	Uncertain significance (Apr 07, 2022)
11-1290264-G-A		not specified	Uncertain significance (Oct 26, 2021)
11-1290298-G-A		not specified	Uncertain significance (Sep 07, 2022)
11-1290340-C-T		not specified	Uncertain significance (Nov 14, 2023)
11-1290342-G-A		not specified	Uncertain significance (Oct 17, 2023)
11-1290360-C-T		not specified	Uncertain significance (Dec 27, 2023)
11-1291476-C-G		Chronic obstructive pulmonary disease • Interstitial lung disease 2 • Combined pulmonary fibrosis-emphysema syndrome	Uncertain significance; association (May 04, 2021)
11-1295682-A-T		not specified	Uncertain significance (Apr 22, 2022)
11-1295760-C-A		not specified	Uncertain significance (Mar 20, 2023)
11-1304599-T-C		Interstitial lung disease 2 • Chronic obstructive pulmonary disease	Uncertain significance (May 04, 2021)
11-1309467-G-C		not specified	Uncertain significance (Jan 10, 2023)
11-1309473-C-T		not specified	Uncertain significance (Aug 12, 2021)
11-1309491-G-A		not specified	Uncertain significance (Jul 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TOLLIP	protein_coding	protein_coding	ENST00000317204	6	35284

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0811	0.910	125678	0	10	125688	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.12	142	185	0.769	0.0000126	1776
Missense in Polyphen		40	68.346	0.58526		600
Synonymous	0.429	77	81.9	0.940	0.00000647	542
Loss of Function	2.27	4	12.7	0.314	6.32e-7	133

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000124	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000554	0.0000544
Finnish	0.0000937	0.0000924
European (Non-Finnish)	0.0000457	0.0000440
Middle Eastern	0.0000554	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the signaling pathway of IL-1 and Toll-like receptors. Inhibits cell activation by microbial products. Recruits IRAK1 to the IL-1 receptor complex. Inhibits IRAK1 phosphorylation and kinase activity (PubMed:11751856). Connects the ubiquitin pathway to autophagy by functioning as a ubiquitin- ATG8 family adapter and thus mediating autophagic clearance of ubiquitin conjugates. The TOLLIP-dependent selective autophagy pathway plays an important role in clearance of cytotoxic polyQ proteins aggregates (PubMed:25042851). {ECO:0000269|PubMed:11751856, ECO:0000269|PubMed:25042851}.
• Pathway: Toll-like receptor signaling pathway - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;Apoptosis Modulation and Signaling;IL-1 signaling pathway;Structural Pathway of Interleukin 1 (IL-1);Toll-like Receptor Signaling;Toll-like Receptor Signaling Pathway;TLR NFkB;Neutrophil degranulation;Signaling by Interleukins;signal transduction through il1r;toll-like receptor pathway;Cytokine Signaling in Immune system;Interleukin-1 signaling;Innate Immune System;Immune System;inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages;IL-1 NFkB;IL-1 p38;IL-1 JNK;IL1;TLR p38;EGFR1;TLR ECSIT MEKK1 JNK;TLR ECSIT MEKK1 p38;TLR JNK;IL1-mediated signaling events;Interleukin-1 family signaling (Consensus)

Recessive Scores

• pRec: 0.144

Intolerance Scores

• loftool: 0.200
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.43

Haploinsufficiency Scores

• pHI: 0.162
• hipred: Y
• hipred_score: 0.801
• ghis: 0.575

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.792

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tollip
• Phenotype: homeostasis/metabolism phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: tollip
• Affected structure: caudal fin
• Phenotype tag: abnormal
• Phenotype quality: curved

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;autophagy;inflammatory response;signal transduction;cell-cell signaling;phosphorylation;epithelial cell differentiation;positive regulation of protein sumoylation;intracellular signal transduction;protein localization to endosome;neutrophil degranulation;innate immune response;leukocyte activation;interleukin-1-mediated signaling pathway
• Cellular component: extracellular region;cytoplasm;cytosol;nuclear body;azurophil granule lumen;specific granule lumen;interleukin-18 receptor complex;interleukin-1 receptor complex;perinuclear region of cytoplasm;extracellular exosome
• Molecular function: interleukin-1, type I receptor binding;protein binding;kinase binding;ubiquitin conjugating enzyme binding;ubiquitin protein ligase binding;SUMO binding;Toll-like receptor binding;ubiquitin binding