SIGIRR

single Ig and TIR domain containing, the group of TIR domain containing|Immunoglobulin like domain containing

Basic information

Region (hg38): 11:405715-417455

Links

ENSG00000185187 ∙ NCBI:59307 ∙ OMIM:605478 ∙ HGNC:30575 ∙ Uniprot:Q6IA17 ∙ 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 SIGIRR gene.

• Inborn genetic diseases (27 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIGIRR 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				2	2	4
missense			27			27
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	27	2	2

Variants in SIGIRR

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

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

Position	Type	Phenotype	Significance	ClinVar
11-405907-C-T		not specified	Uncertain significance (Jan 08, 2024)
11-405926-G-T		not specified	Uncertain significance (Mar 07, 2024)
11-405958-C-G		not specified	Uncertain significance (Jun 21, 2021)
11-405980-G-A			Likely benign (May 16, 2018)
11-405994-C-G		not specified	Uncertain significance (Dec 03, 2021)
11-406024-G-C		not specified	Uncertain significance (Aug 23, 2021)
11-406054-G-A		not specified	Uncertain significance (Oct 30, 2023)
11-406351-A-T		not specified	Uncertain significance (Jul 26, 2021)
11-406387-A-C		not specified	Uncertain significance (Oct 12, 2022)
11-406440-G-T		not specified	Uncertain significance (Mar 24, 2023)
11-406441-T-C		not specified	Uncertain significance (Mar 24, 2023)
11-406459-G-A		not specified	Uncertain significance (Sep 20, 2023)
11-406492-C-T		not specified	Uncertain significance (Jun 07, 2023)
11-406528-G-A		not specified	Uncertain significance (May 05, 2023)
11-406529-A-T		not specified	Uncertain significance (May 05, 2023)
11-406531-G-A		not specified	Uncertain significance (Nov 18, 2023)
11-406892-C-A		not specified	Uncertain significance (Oct 26, 2022)
11-406921-G-A			Likely benign (Jun 29, 2018)
11-406935-C-A		not specified	Uncertain significance (Nov 05, 2021)
11-407126-G-C		not specified	Uncertain significance (Oct 29, 2021)
11-407131-C-A		not specified	Uncertain significance (Mar 03, 2022)
11-407143-A-G		not specified	Uncertain significance (Feb 28, 2024)
11-407162-G-A		not specified	Uncertain significance (May 17, 2023)
11-407529-C-T		not specified	Uncertain significance (Oct 20, 2023)
11-407550-G-A		not specified	Uncertain significance (Dec 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SIGIRR	protein_coding	protein_coding	ENST00000431843	9	11740

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000593	0.892	125318	1	97	125416	0.000391

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0485	242	240	1.01	0.0000136	2568
Missense in Polyphen		89	80.176	1.1101		871
Synonymous	-1.49	133	113	1.18	0.00000699	879
Loss of Function	1.56	11	18.2	0.605	9.29e-7	198

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000890	0.000879
Ashkenazi Jewish	0.000533	0.000498
East Asian	0.000231	0.000218
Finnish	0.00	0.00
European (Non-Finnish)	0.000596	0.000521
Middle Eastern	0.000231	0.000218
South Asian	0.0000657	0.0000653
Other	0.00103	0.000980

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a negative regulator of the Toll-like and IL-1R receptor signaling pathways. Attenuates the recruitment of receptor-proximal signaling components to the TLR4 receptor, probably through an TIR-TIR domain interaction with TLR4. Through its extracellular domain interferes with the heterodimerization of Il1R1 and IL1RAP. {ECO:0000269|PubMed:12925853, ECO:0000269|PubMed:14715412, ECO:0000269|PubMed:15866876, ECO:0000269|PubMed:25963006}.
• Pathway: Regulation of toll-like receptor signaling pathway;Signaling by Interleukins;Cytokine Signaling in Immune system;Toll-Like Receptors Cascades;Innate Immune System;Immune System;Toll Like Receptor 4 (TLR4) Cascade;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;Interleukin-37 signaling;Interleukin-1 family signaling (Consensus)

Recessive Scores

• pRec: 0.121

Intolerance Scores

• loftool: 0.738
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58.85

Haploinsufficiency Scores

• pHI: 0.114
• hipred: Y
• hipred_score: 0.596
• ghis: 0.410

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.327

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sigirr
• Phenotype: hematopoietic system phenotype; immune system phenotype; digestive/alimentary phenotype; cellular phenotype

Gene ontology

• Biological process: negative regulation of cytokine-mediated signaling pathway;acute-phase response;signal transduction;negative regulation of lipopolysaccharide-mediated signaling pathway;negative regulation of DNA-binding transcription factor activity;negative regulation of chemokine biosynthetic process;cellular response to cytokine stimulus
• Cellular component: plasma membrane;membrane;integral component of membrane
• Molecular function: protein binding