IL1RAPL1

Protein identityUniProt · HPA

UniProt accession

Q9NZN1

Gene

IL1RAPL1

Ensembl

ENSG00000169306

Chromosome

X

Canonical length

696 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted membrane proteins

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene is a member of the interleukin 1 receptor family and is similar to the interleukin 1 accessory proteins. This protein has an N-terminal signal peptide, three extracellular immunoglobulin Ig-like domains, a transmembrane domain, an intracellular Toll/IL-1R domain, and a long C-terminal tail which interacts with multiple signalling molecules. This gene is located at a region on chromosome X that is associated with a non-syndromic form of X-linked intellectual disability. Deletions and mutations in this gene were found in patients with intellectual disability. This gene is expressed at a high level in post-natal brain structures involved in the hippocampal memory system, which suggests a specialized role in the physiological processes underlying memory and learning abilities, and plays a role in synapse formation and stabilization. [provided by RefSeq, Jul 2017]

Canonical amino-acid sequenceUniProt

696 residues, UniProt reviewed canonical sequence.

>Q9NZN1|IL1RAPL1
     1  MKAPIPHLIL LYATFTQSLK VVTKRGSADG CTDWSIDIKK YQVLVGEPVR IKCALFYGYI
    61  RTNYSLAQSA GLSLMWYKSS GPGDFEEPIA FDGSRMSKEE DSIWFRPTLL QDSGLYACVI
   121  RNSTYCMKVS ISLTVGENDT GLCYNSKMKY FEKAELSKSK EISCRDIEDF LLPTREPEIL
   181  WYKECRTKTW RPSIVFKRDT LLIREVREDD IGNYTCELKY GGFVVRRTTE LTVTAPLTDK
   241  PPKLLYPMES KLTIQETQLG DSANLTCRAF FGYSGDVSPL IYWMKGEKFI EDLDENRVWE
   301  SDIRILKEHL GEQEVSISLI VDSVEEGDLG NYSCYVENGN GRRHASVLLH KRELMYTVEL
   361  AGGLGAILLL LVCLVTIYKC YKIEIMLFYR NHFGAEELDG DNKDYDAYLS YTKVDPDQWN
   421  QETGEEERFA LEILPDMLEK HYGYKLFIPD RDLIPTGTYI EDVARCVDQS KRLIIVMTPN
   481  YVVRRGWSIF ELETRLRNML VTGEIKVILI ECSELRGIMN YQEVEALKHT IKLLTVIKWH
   541  GPKCNKLNSK FWKRLQYEMP FKRIEPITHE QALDVSEQGP FGELQTVSAI SMAAATSTAL
   601  ATAHPDLRST FHNTYHSQMR QKHYYRSYEY DVPPTGTLPL TSIGNQHTYC NIPMTLINGQ
   661  RPQTKSSREQ NPDEAHTNSA ILPLLPRETS ISSVIW

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IL1RAPL1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.39

Highest tissue expression

2.9 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IL1RAPL1.

Disease | AllUniProt

Conditions IL1RAPL1 is implicated in, by any mechanism.

• Intellectual developmental disorder, X-linked 21 (XLID21) MIM:300143

Disease | GeneticClinVar

32 pathogenic / likely-pathogenic of 357 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Intellectual disability, X-linked 21
• See cases
• Intellectual disability
• Inborn genetic diseases
• IL1RAPL1-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.2

gnomAD pLI

1

gnomAD missense Z

2.77

DepMap mean gene effect

0.04

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell surface receptor signaling pathway
• negative regulation of exocytosis
• neuron differentiation
• positive regulation of dendritic spine morphogenesis
• positive regulation of synapse assembly
• presynaptic membrane assembly
• regulation of neuron projection development
• regulation of postsynapse organization
• regulation of presynapse assembly
• synaptic membrane adhesion
• trans-synaptic signaling by trans-synaptic complex

Molecular functions

• NAD+ nucleosidase activity, cyclic ADP-ribose generating
• signaling receptor binding

Cellular components

• axon
• cell surface
• cytoplasm
• dendrite
• glutamatergic synapse
• plasma membrane
• postsynaptic membrane

Protein domainsUniProt · Pfam · InterPro

• Toll/interleukin-1 receptor homology (TIR) domain
• Immunoglobulin subtype 2
• Immunoglobulin domain subtype
• Immunoglobulin-like domain
• Immunoglobulin-like beta-sandwich domain
• Immunoglobulin-like fold
• Interleukin-1 receptor family
• Toll/interleukin-1 receptor homology (TIR) domain superfamily
• Immunoglobulin-like domain superfamily
• IL-1Ra-like, immunoglobulin domain
• Immunoglobulin domain
• TIR domain
• Immunoglobulin domain

KeywordsUniProt

• Cell membrane
• Cell projection
• Cytoplasm
• Disulfide bond
• Glycoprotein
• Hydrolase
• Immunoglobulin domain
• Intellectual disability
• Membrane
• NAD
• Receptor
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of IL1RAPL1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• NCS1