IL1RAPL1 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- IL1RAPL1 (HGNC:5996) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- interleukin 1 receptor accessory protein like 1
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- IL1RAPL, MRX34, MRX21, MRX10
- Alias symbols
- OPHN4, TIGIRR-2, IL1R8, IL1RAPL-1
- %HI
- 1.75(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 1(Read more about gnomAD pLI score)
- LOEUF
- 0.2(Read more about gnomAD LOEUF score)
- Cytoband
- Xp21.3-p21.2
- Genomic Coordinates
-
GRCh37/hg19: chrX:28605563-29974835 NCBI Ensembl UCSC GRCh38/hg38: chrX:28587446-29956718 NCBI Ensembl UCSC - MANE Select Transcript
- NM_014271.4 ENST00000378993.6 (Read more about MANE Select)
- 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:127... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- intellectual disability, X-linked 21 Monarch
-
PUBMED:
26350204
Grozeva et al (2015) performed targeted next gen sequencing for 565 genes in 986 individuals with moderate to severe intellectual disability. Three affected males were identified with predicted loss of function variants (c.148C>T/p.R50*); (c.889C>T/p.R297*); (c.606dupT/p.Ile203Tyrfs*8).
-
PUBMED:
21484992
Franek et al (2011) reported a family consisting of two brothers with moderate intellectual disability, seizures, and dysmorphic features. Through targeted sequencing of nine known X-linked intellectual disability genes, both brothers were found to have a maternally inherited deletion of exons 1-5 of IL1RAPL1 (2-6 in the updated transcript NM_014271.4), which includes the first coding exon and is predicted to result in complete absence of protein product.
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PUBMED:
21271657
Behnecke et al (2011) reported a male individual with intellectual disability, global delays, dysmorphic features, scoliosis, and strabismus who had a de novo 300 kb intragenic deletion, which includes exon 2 of the gene, which is the first coding exon and includes the start methionine.
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PUBMED:
25167861
Redin et al (2014) reported a proband with moderate intellectual disability who was found to have a maternally inherited 10 bp deletion c.894_903 (p.Trp299Thrfs*18). A similarly affected brother was then found to have a de novo hemizygous deletion of the entire exon 7, which would be predicted to be out of frame. This deletion was found to have originated on the maternal allele, suggesting that the inherited 10 bp deletion that the mother carried may predispose to genomic instability leading to the larger deletion event. Both variants in this family would be predicted to result in loss of function.
-
PUBMED:
18801879
Piton et al (2008) sequenced IL1RAPL1 in a cohort of 142 individuals with autism spectrum disorder and reported a de novo frameshifting variant in exon 9 (p.Ile367Serfs*9) in a female with a diagnosis of Asperger syndrome. Functional studies showed that this resulted in loss of function. In addition, authors reported a male proband with intellectual disability and autistic features, who had two brothers, one with pervasive developmental disorder - not otherwise specified, and the other with mild intellectual disability and repetitive behaviors. All three were found to have a deletion in IL1RAPL1, spanning exons 3-7. This is predicted to result a frameshift (p.Ala28Glufs*15), truncating the majority of the protein and leading to loss of function. This deletion was found to be inherited from the reportedly unaffected mother.
-
PUBMED:
22031302
Mikhail et al. (2011) reported a male individual with global developmental delay, intellectual disability, and dysmorphic facial features who had a 1.07 Mb intragenic deletion detected via array CGH that contains exons 2-6 that was inherited from a reportedly unaffected mother. Exon 2 is the first coding exon of this gene; this deletion includes the start methionine and would be predicted to result in loss of function.
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.