IL1RAPL1

interleukin 1 receptor accessory protein like 1, the group of TIR domain containing|MicroRNA protein coding host genes|I-set domain containing|Interleukin receptors

Basic information

Region (hg38): X:28587446-29956718

Previous symbols: [ "IL1RAPL", "MRX34", "MRX21", "MRX10" ]

Links

ENSG00000169306NCBI:11141OMIM:300206HGNC:5996Uniprot:Q9NZN1AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • intellectual disability, X-linked 21 (Definitive), mode of inheritance: XLR
  • intellectual disability, X-linked 21 (Strong), mode of inheritance: XL
  • intellectual disability, X-linked 21 (Moderate), mode of inheritance: XL
  • non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
  • intellectual disability, X-linked 21 (Definitive), mode of inheritance: XL
  • non-syndromic X-linked intellectual disability (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Intellectual developmental disorder, X-linked 21XLGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic8230164; 10471494; 16470793; 18005360; 19012350; 18801879; 21484992

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IL1RAPL1 gene.

  • not provided (4 variants)
  • Intellectual disability, X-linked 21 (2 variants)
  • Intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IL1RAPL1 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
4
clinvar
34
clinvar
11
clinvar
49
missense
1
clinvar
67
clinvar
11
clinvar
2
clinvar
81
nonsense
2
clinvar
5
clinvar
1
clinvar
8
start loss
0
frameshift
2
clinvar
4
clinvar
6
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
2
clinvar
1
clinvar
3
splice region
3
7
2
12
non coding
7
clinvar
22
clinvar
26
clinvar
55
Total 6 12 79 67 39

Variants in IL1RAPL1

This is a list of pathogenic ClinVar variants found in the IL1RAPL1 region.

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

Position Type Phenotype Significance ClinVar
X-28587667-T-A Intellectual disability, X-linked 21 Uncertain significance (Jan 13, 2018)368180
X-28587670-G-A Intellectual disability, X-linked 21 Uncertain significance (Jan 12, 2018)368181
X-28587759-GT-G Non-syndromic X-linked intellectual disability Benign (Jun 14, 2016)368183
X-28587759-GTT-G Non-syndromic X-linked intellectual disability Uncertain significance (Jun 14, 2016)368184
X-28587759-G-GT Non-syndromic X-linked intellectual disability Uncertain significance (Jun 14, 2016)368182
X-28587990-C-A Intellectual disability, X-linked 21 Uncertain significance (Jan 13, 2018)368185
X-28588033-G-A Intellectual disability, X-linked 21 Benign (Jan 12, 2018)368186
X-28588061-A-C Intellectual disability, X-linked 21 Benign (Jan 12, 2018)912343
X-28588078-A-C Uncertain significance (Nov 29, 2022)2429011
X-28789228-G-A Benign (Jul 03, 2018)1236336
X-28789324-C-T Intellectual disability, X-linked 21 Benign (May 25, 2020)368187
X-28789325-G-A not specified • Intellectual disability, X-linked 21 Benign (Aug 19, 2021)281021
X-28789354-C-T Benign/Likely benign (Jul 01, 2024)2056458
X-28789355-G-A Intellectual disability, X-linked 21 • History of neurodevelopmental disorder Benign/Likely benign (Dec 21, 2023)368188
X-28789364-C-T Benign (Sep 23, 2022)2075870
X-28789368-A-G Uncertain significance (Mar 29, 2023)2848853
X-28789379-C-T Intellectual disability, X-linked 21 • not specified Benign (Jan 24, 2024)368189
X-28789402-A-G Likely benign (Mar 01, 2024)3067362
X-28789404-G-T Uncertain significance (Oct 01, 2019)872758
X-28789425-G-A Intellectual disability, X-linked 21 Conflicting classifications of pathogenicity (Jan 19, 2024)2432844
X-28789427-T-C Intellectual disability, X-linked 21 Likely pathogenic (Jun 13, 2024)3251939
X-28789631-A-G Benign (Jul 03, 2018)1237882
X-28789652-T-C Benign (Jul 03, 2018)1283349
X-28789659-A-G Benign (Nov 20, 2018)1224200
X-28852969-C-G Benign (May 12, 2021)1294759

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
IL1RAPL1protein_codingprotein_codingENST00000378993 101369325
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9990.00114125709021257110.00000795
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.771402670.5240.00002024572
Missense in Polyphen36120.020.299952089
Synonymous-0.006579796.91.000.000007611300
Loss of Function4.36124.10.04150.00000182424

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00002450.0000176
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: May regulate secretion and presynaptic differentiation through inhibition of the activity of N-type voltage-gated calcium channel (PubMed:12783849). May activate the MAP kinase JNK (PubMed:15123616). Plays a role in neurite outgrowth (By similarity). During dendritic spine formation can bidirectionally induce pre- and post-synaptic differentiation of neurons by trans- synaptically binding to PTPRD (By similarity). {ECO:0000250|UniProtKB:P59823, ECO:0000250|UniProtKB:P59824, ECO:0000269|PubMed:12783849, ECO:0000269|PubMed:15123616}.;
Pathway
Signaling by Interleukins;Cytokine Signaling in Immune system;Immune System;Neuronal System;Receptor-type tyrosine-protein phosphatases;Protein-protein interactions at synapses;Interleukin-38 signaling;Interleukin-1 family signaling (Consensus)

Recessive Scores

pRec
0.227

Intolerance Scores

loftool
rvis_EVS
-0.6
rvis_percentile_EVS
17.75

Haploinsufficiency Scores

pHI
0.788
hipred
Y
hipred_score
0.717
ghis
0.482

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
gene_indispensability_pred
E
gene_indispensability_score
0.801

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Il1rapl1
Phenotype
nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);

Zebrafish Information Network

Gene name
il1rapl1b
Affected structure
olfactory receptor cell
Phenotype tag
abnormal
Phenotype quality
increased size

Gene ontology

Biological process
heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules;signal transduction;regulation of neuron projection development;neuron differentiation;negative regulation of exocytosis;positive regulation of dendrite morphogenesis;positive regulation of synapse assembly;calcium ion transmembrane transport;cellular response to cytokine stimulus;presynaptic membrane assembly;regulation of postsynapse organization;trans-synaptic signaling by trans-synaptic complex;regulation of presynapse assembly
Cellular component
cytoplasm;plasma membrane;cell surface;integral component of membrane;axon;dendrite;postsynaptic membrane;glutamatergic synapse
Molecular function
signaling receptor binding;voltage-gated calcium channel activity;protein binding;interleukin-1 binding