IRAK1BP1

Chr 6

interleukin 1 receptor associated kinase 1 binding protein 1

Also known as: AIP70, SIMPL

NCBI Gene: 134728 ENSG00000146243 UniProt: Q5VVH5

The protein acts as a signaling adaptor that enhances NF-kappaB transcriptional activity and is required for cell survival through the TNFRSF1A pathway. Mutations cause autosomal recessive immunodeficiency, with patients presenting in infancy with severe bacterial and viral infections. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

ResearchSummary from RefSeq, UniProt

Predicted to enable signaling adaptor activity. Predicted to be involved in canonical NF-kappaB signal transduction. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2025]

ResearchGenerating clinical summary…

LOEUF 1.40

Clinical Summary— IRAK1BP1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

63 unique Pathogenic / Likely Pathogenic· 300 VUS of 666 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.40LOEUF

pLI 0.000

Z-score 0.56

OE 0.83 (0.51–1.40)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.60Z-score

OE missense 1.14 (1.00–1.30)

159 obs / 139.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.83 (0.51–1.40)

0≤0.351.4

Missense OE?1.14 (1.00–1.30)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 10 / 12.1Missense obs/exp: 159 / 139.1Syn Z: -0.13

ClinVar Variant Classifications

666 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29

Likely Pathogenic34

VUS300

Likely Benign207

Benign58

Conflicting23

Pathogenic

Likely Pathogenic

300

VUS

207

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	27	0	2	0	29
Likely Pathogenic	28	5	1	0	34
VUS	13	259	25	3	300
Likely Benign	0	27	76	104	207
Benign	0	17	30	11	58
Conflicting	—				23
Total	68	308	134	118	651

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

14 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap IRAK1BP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →