SIGIRR

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar	2 clinvar	4
missense			69 clinvar	2 clinvar		71
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	71	4	2	77

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 71 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001135054.2	RefSeq	NP_001128526.1	9	MANE Select
ENST00000431843.7	Ensembl	ENSP00000403104.2	9	MANE Select
NM_001135053.2	RefSeq	NP_001128525.1	9	Standard
NM_021805.3	RefSeq	NP_068577.2	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Regulation of toll-like receptor signaling pathway
Signaling by Interleukins
Cytokine Signaling in Immune system
Toll-Like Receptors Cascades
Innate Immune System

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

Molecular Function

protein binding

Cellular Component

plasma membrane
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000431843
Coding exons: 9
Length: 11740
Individuals with no LoFs: 125318
Homozygous LoFs: 1
Heterozygous LoFs: 97
Defined: 125416
p: 0.000391

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0485	242	240	1.01	0.0000136	2568
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00038	0.00037	rare
Latino/Admixed American	0.00051	0.00046	rare
Ashkenazi Jewish	0.00053	0.00050	rare
East Asian	0.00023	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00060	0.00052	rare
South Asian	0.000066	0.000065	rare
Other	0.0010	0.00098	notable

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.121

Intolerance Scores

LoFtool: 0.738
RVIS EVS: 0.06
RVIS percentile EVS: 58.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.327

Gene Damage Prediction

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