TLR8

toll like receptor 8, the group of CD molecules|Toll like receptors

Basic information

Region (hg38): X:12906619-12923169

Links

ENSG00000101916 ∙ NCBI:51311 ∙ OMIM:300366 ∙ HGNC:15632 ∙ Uniprot:Q9NR97 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 98 with autoinflammation, X-linked (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 98 with autoinflammation, X-linked	XL	Allergy/Immunology/Infectious	Individuals may be susceptible to infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; HSCT has been described	Allergy/Immunology/Infectious	33512449; 34981838; 35477763

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TLR8 gene.

• Inborn genetic diseases (15 variants)
• not provided (13 variants)
• not specified (5 variants)
• Immunodeficiency 98 with autoinflammation, X-linked (2 variants)
• Autoimmune hemolytic anemia;Systemic autoinflammation (2 variants)
• INFLTR8 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TLR8 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				3	6	9
missense	1		19		1	21
nonsense						0
start loss					1	1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	1	0	19	3	8

Variants in TLR8

This is a list of pathogenic ClinVar variants found in the TLR8 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-12906707-A-G		not specified	Benign (Jan 24, 2024)
X-12919052-G-T			Uncertain significance (Mar 01, 2024)
X-12919092-A-G		not specified	Conflicting classifications of pathogenicity (May 09, 2022)
X-12919114-G-A		not specified	Uncertain significance (Nov 12, 2021)
X-12919119-G-A		not specified	Conflicting classifications of pathogenicity (Dec 01, 2022)
X-12919236-A-G		not specified	Uncertain significance (Jan 09, 2024)
X-12919236-A-T		not specified	Uncertain significance (Nov 08, 2022)
X-12919339-T-C		not specified	Uncertain significance (Jan 17, 2024)
X-12919394-C-T		not specified	Benign (Jan 24, 2024)
X-12919417-A-C		not specified	Uncertain significance (Nov 07, 2022)
X-12919419-C-A		not specified	Uncertain significance (Aug 08, 2023)
X-12919601-C-T			Benign (Aug 16, 2018)
X-12919602-G-A		not specified	Uncertain significance (Mar 31, 2022)
X-12919675-C-T		not specified	Uncertain significance (Sep 14, 2021)
X-12919685-C-T		not specified	Benign (Jan 24, 2024)
X-12919693-C-A			Uncertain significance (Nov 22, 2022)
X-12920212-T-C			Uncertain significance (May 01, 2022)
X-12920267-C-T			Likely benign (Jun 20, 2018)
X-12920335-C-T		INFLTR8 • Immunodeficiency 98 with autoinflammation, X-linked	Uncertain significance (Apr 22, 2021)
X-12920336-G-T			Likely benign (Oct 01, 2023)
X-12920522-C-A		INFLTR8 • Immunodeficiency 98 with autoinflammation, X-linked	Pathogenic (May 04, 2022)
X-12920592-G-A			Uncertain significance (May 01, 2022)
X-12920703-G-T		not specified	Uncertain significance (May 27, 2022)
X-12920755-G-A		INFLTR8 • Immunodeficiency 98 with autoinflammation, X-linked	Pathogenic (May 04, 2022)
X-12920755-G-T		Autoimmune hemolytic anemia;Systemic autoinflammation • Immunodeficiency 98 with autoinflammation, X-linked	Pathogenic (Feb 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TLR8	protein_coding	protein_coding	ENST00000218032	2	16550

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.324	0.676	125679	5	8	125692	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.08	218	389	0.560	0.0000300	6923
Missense in Polyphen		31	121.33	0.2555		2399
Synonymous	-0.0189	154	154	1.00	0.0000118	2003
Loss of Function	3.31	5	21.6	0.231	0.00000171	410

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000760	0.0000615
Ashkenazi Jewish	0.000273	0.000198
East Asian	0.00	0.00
Finnish	0.000188	0.000139
European (Non-Finnish)	0.0000740	0.0000528
Middle Eastern	0.00	0.00
South Asian	0.0000531	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. {ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:23520111}.
• Pathway: Toll-like receptor signaling pathway - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;Toll-like Receptor Signaling;Simplified Depiction of MYD88 Distinct Input-Output Pathway;Toll-like Receptor Signaling Pathway;Toll Like Receptor 7/8 (TLR7/8) Cascade;TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling;Toll Like Receptor 9 (TLR9) Cascade;Trafficking and processing of endosomal TLR;Toll-Like Receptors Cascades;Innate Immune System;Immune System;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;MyD88 dependent cascade initiated on endosome (Consensus)

Recessive Scores

• pRec: 0.193

Intolerance Scores

• loftool: 0.288
• rvis_EVS: -0.24
• rvis_percentile_EVS: 36.17

Haploinsufficiency Scores

• pHI: 0.125
• hipred: N
• hipred_score: 0.481
• ghis: 0.491

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.962

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tlr8
• Phenotype: immune system phenotype; renal/urinary system phenotype; hematopoietic system phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: microglial cell activation;regulation of protein phosphorylation;toll-like receptor signaling pathway;MyD88-dependent toll-like receptor signaling pathway;immune response;I-kappaB kinase/NF-kappaB signaling;response to virus;immunoglobulin mediated immune response;positive regulation of interleukin-6 production;toll-like receptor 8 signaling pathway;toll-like receptor 9 signaling pathway;positive regulation of interferon-gamma biosynthetic process;innate immune response;positive regulation of innate immune response;positive regulation of interferon-alpha biosynthetic process;positive regulation of interferon-beta biosynthetic process;positive regulation of interleukin-8 biosynthetic process;positive regulation of interleukin-1 beta secretion;defense response to virus;cellular response to mechanical stimulus;positive regulation of interleukin-6 secretion;negative regulation of interleukin-12 secretion
• Cellular component: Golgi membrane;endoplasmic reticulum membrane;plasma membrane;external side of plasma membrane;endosome membrane;integral component of membrane;endolysosome membrane
• Molecular function: DNA binding;RNA binding;double-stranded RNA binding;single-stranded RNA binding;transmembrane signaling receptor activity;drug binding;signaling pattern recognition receptor activity;signaling receptor activity