IRAK1

Chr Xq28

interleukin 1 receptor associated kinase 1

Aliases:: IRAK, pelle
MANE:: ENST00000369980.8

OMIM: 300283 ↗NCBI: 3654 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

IRAK1 · P51617

v62025-08-01

Predicted Aligned Error matrix for IRAK1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

68.6/ 100

Low

712 residues

Confidence breakdown

Very high(≥ 90)38%
Confident(70–90)18%
Low(50–70)7%
Very low(< 50)38%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

COVID-19 research
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability
Unknown
Primary immunodeficiency or monogenic inflammatory bowel disease
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Disease associations (Open Targets)

myelofibrosis
0.49
primary myelofibrosis
0.48
systemic lupus erythematosus
0.41
neoplasm
0.40
neurodegenerative disease
0.38
acquired polycythemia vera
0.37
plasma cell myeloma
0.37
autoimmune disorder of central nervous system
0.37
rheumatoid arthritis
0.34
Rett syndrome
0.34

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Interleukin-1 receptor-associated kinase 1

Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3