TLR7

toll like receptor 7, the group of Toll like receptors

Basic information

Region (hg38): X:12867071-12890361

Links

ENSG00000196664 ∙ NCBI:51284 ∙ OMIM:300365 ∙ HGNC:15631 ∙ Uniprot:Q9NYK1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 74, COVID-19-related, X-linked (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 74, COVID-19 related, X-linked	XL	Allergy/Immunology/Infectious	Individuals with Immunodeficiency 74, COVID-19 related, X-linked, may demonstrate susceptibility to severe COVID-19, and awareness may allow preventative measures (such as adhering to practices to reduce the chance of infection); Individuals with Systemic lupus erythematosus have been described as benefiting from medical management (eg, with prednisone, azathioprine, mycophenolate, rituximab, immunoglobulins, Etanercept)	Allergy/Immunology/Infectious	32706371; 35477763

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TLR7 gene.

• not provided (116 variants)
• Inborn genetic diseases (17 variants)
• Systemic lupus erythematosus (1 variants)
• not specified (1 variants)
• Systemic lupus erythematosus 17 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TLR7 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				41	12	53
missense			67	3	4	74
nonsense			1			1
start loss						0
frameshift			2			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	71	44	16

Variants in TLR7

This is a list of pathogenic ClinVar variants found in the TLR7 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-12885537-G-A			Uncertain significance (Jun 20, 2022)
X-12885540-A-T		not specified	Benign (Feb 01, 2024)
X-12885590-A-G		Systemic lupus erythematosus 17	Pathogenic (May 10, 2022)
X-12885591-G-T			Uncertain significance (Dec 02, 2023)
X-12885592-A-G			Likely benign (May 17, 2023)
X-12885616-T-C			Likely benign (Nov 02, 2023)
X-12885631-T-G			Uncertain significance (Nov 28, 2023)
X-12885639-A-G			Uncertain significance (Jul 31, 2023)
X-12885652-C-T			Likely benign (May 15, 2023)
X-12885692-G-A			Uncertain significance (Jun 27, 2022)
X-12885701-A-G			Uncertain significance (Jan 25, 2024)
X-12885703-G-A			Likely benign (May 19, 2022)
X-12885730-T-G			Uncertain significance (Dec 25, 2023)
X-12885753-C-T		not specified	Uncertain significance (Nov 12, 2021)
X-12885756-C-T			Uncertain significance (Nov 18, 2023)
X-12885757-G-A			Likely benign (Dec 13, 2023)
X-12885774-A-G		not specified	Uncertain significance (Jun 02, 2023)
X-12885776-C-T			Uncertain significance (Jan 28, 2023)
X-12885782-G-A		TLR7-related disorder • not specified	Conflicting classifications of pathogenicity (Nov 13, 2023)
X-12885790-C-T			Likely benign (Mar 01, 2023)
X-12885802-C-T			Likely benign (Jul 12, 2023)
X-12885811-A-G			Likely benign (Feb 21, 2023)
X-12885840-T-C			Uncertain significance (Sep 04, 2023)
X-12885845-A-T			Uncertain significance (Dec 13, 2023)
X-12885857-C-A		not specified	Uncertain significance (Mar 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TLR7	protein_coding	protein_coding	ENST00000380659	2	23298

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.979	0.0209	125735	4	5	125744	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.01	205	368	0.558	0.0000261	6976
Missense in Polyphen		42	127.94	0.32828		2454
Synonymous	-0.527	157	149	1.05	0.0000109	2020
Loss of Function	3.80	2	20.7	0.0968	0.00000143	428

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000113	0.0000981
Ashkenazi Jewish	0.000268	0.000198
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000244	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.000169	0.0000980
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. TLR7 is a nucleotide-sensing TLR which is activated by single-stranded RNA. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (By similarity). {ECO:0000250, ECO:0000269|PubMed:18250417}.
• Pathway: Influenza A - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);Measles - 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 pathway;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: 0.287

Intolerance Scores

• loftool: 0.271
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.85

Haploinsufficiency Scores

• pHI: 0.134
• hipred: Y
• hipred_score: 0.749
• ghis: 0.571

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.122

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tlr7
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; renal/urinary system phenotype; 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); hematopoietic system 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;I-kappaB phosphorylation;positive regulation of chemokine production;positive regulation of interleukin-6 production;positive regulation of interleukin-8 production;toll-like receptor 7 signaling pathway;toll-like receptor 9 signaling pathway;positive regulation of interferon-gamma biosynthetic process;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 inflammatory response;defense response to virus;cellular response to mechanical stimulus;positive regulation of NIK/NF-kappaB signaling
• Cellular component: Golgi membrane;cytoplasm;lysosome;endosome;endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;endosome membrane;integral component of membrane;early phagosome;endolysosome membrane;receptor complex
• Molecular function: double-stranded RNA binding;single-stranded RNA binding;transmembrane signaling receptor activity;drug binding;signaling pattern recognition receptor activity;siRNA binding