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:28587445-29956718

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

Links

ENSG00000169306 ∙ NCBI:11141 ∙ OMIM:300206 ∙ HGNC:5996 ∙ Uniprot:Q9NZN1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked 21	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	8230164; 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 (151 variants)
• Intellectual disability, X-linked 21 (40 variants)
• Inborn genetic diseases (18 variants)
• not specified (10 variants)
• Non-syndromic X-linked intellectual disability (4 variants)
• IL1RAPL1-related condition (3 variants)
• Intellectual disability (2 variants)
• See cases (2 variants)
• IL1RAPL1-Related Disorder (1 variants)
• Developmental disorder (1 variants)
• History of neurodevelopmental disorder (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			5	28	10	43
missense		1	59	9	1	70
nonsense	2	5	1			8
start loss						0
frameshift	2	4				6
inframe indel		1				1
splice donor/acceptor (+/-2bp)	2	1				3
splice region			3	5	3	11
non coding			7	19	26	52
Total	6	12	72	56	37

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)
X-28587670-G-A		Intellectual disability, X-linked 21	Uncertain significance (Jan 12, 2018)
X-28587759-GT-G		Non-syndromic X-linked intellectual disability	Benign (Jun 14, 2016)
X-28587759-GTT-G		Non-syndromic X-linked intellectual disability	Uncertain significance (Jun 14, 2016)
X-28587759-G-GT		Non-syndromic X-linked intellectual disability	Uncertain significance (Jun 14, 2016)
X-28587990-C-A		Intellectual disability, X-linked 21	Uncertain significance (Jan 13, 2018)
X-28588033-G-A		Intellectual disability, X-linked 21	Benign (Jan 12, 2018)
X-28588061-A-C		Intellectual disability, X-linked 21	Benign (Jan 12, 2018)
X-28588078-A-C			Uncertain significance (Nov 29, 2022)
X-28789228-G-A			Benign (Jul 03, 2018)
X-28789324-C-T		Intellectual disability, X-linked 21	Benign (May 25, 2020)
X-28789325-G-A		not specified • Intellectual disability, X-linked 21	Benign (Aug 19, 2021)
X-28789354-C-T			Benign (Jul 20, 2022)
X-28789355-G-A		Intellectual disability, X-linked 21 • History of neurodevelopmental disorder	Benign/Likely benign (Dec 21, 2023)
X-28789364-C-T			Benign (Sep 23, 2022)
X-28789368-A-G			Uncertain significance (Mar 29, 2023)
X-28789379-C-T		Intellectual disability, X-linked 21 • not specified	Benign (Jan 24, 2024)
X-28789402-A-G			Likely benign (Mar 01, 2024)
X-28789404-G-T			Uncertain significance (Oct 01, 2019)
X-28789425-G-A		Intellectual disability, X-linked 21	Conflicting classifications of pathogenicity (Jan 19, 2024)
X-28789631-A-G			Benign (Jul 03, 2018)
X-28789652-T-C			Benign (Jul 03, 2018)
X-28789659-A-G			Benign (Nov 20, 2018)
X-28852969-C-G			Benign (May 12, 2021)
X-28853122-C-G			Likely benign (May 15, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IL1RAPL1	protein_coding	protein_coding	ENST00000378993	10	1369325

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00114	125709	0	2	125711	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.77	140	267	0.524	0.0000202	4572
Missense in Polyphen		36	120.02	0.29995		2089
Synonymous	-0.00657	97	96.9	1.00	0.00000761	1300
Loss of Function	4.36	1	24.1	0.0415	0.00000182	424

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000245	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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

• 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
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

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