TOLLIP

toll interacting protein, the group of C2 domain containing

Basic information

Region (hg38): 11:1274371-1309654

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.

not_specified (37 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. These statistics are base on transcript: NM_000019009.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			35 clinvar	1 clinvar	1 clinvar	37
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	35	2	1

Loading clinvar variants...

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