OPHN1 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- OPHN1 (HGNC:8148) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- oligophrenin 1
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- MRX60
- Alias symbols
- OPN1, ARHGAP41
- %HI
- 35.46(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 1(Read more about gnomAD pLI score)
- LOEUF
- 0.16(Read more about gnomAD LOEUF score)
- Cytoband
- Xq12
- Genomic Coordinates
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GRCh37/hg19: chrX:67262186-67653337 NCBI Ensembl UCSC GRCh38/hg38: chrX:68042344-68433841 NCBI Ensembl UCSC - MANE Select Transcript
- NM_002547.3 ENST00000355520.6 (Read more about MANE Select)
- Function
- Stimulates GTP hydrolysis of members of the Rho family. Its action on RHOA activity and signaling is implicated in growth and stabilization of dendritic spines, and therefore in synaptic function. Critical for the stabilization of AMPA receptors at postsynaptic sites. Critical for the regulation of synaptic vesicle endocytosis at presynaptic terminals. Required for the localization of NR1D1 to dendrites, can suppress its repressor activity and protect it from proteasomal degradation (By similari... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- X-linked intellectual disability-cerebellar hypoplasia syndrome Monarch
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PUBMED:
16221952
Zanni et al. (2005) reported loss of function variants in four families. In family A, a IVS2+2T>C splice site variant was found in a 6-year old boy with hypotonia, strabismus, nystagmus, developmental delay, intellectual disability, and ataxic gait. This variant led to skipping of exon 2 and a frameshift. No normal transcripts were detected. It was inherited from an unaffected mother. In family B, a deletion of exons 16 and 17 was found in six affected males whose features included intellectual disability, dysmorphic features, hypoplastic cerebellar vermis, and seizures. Carrier females were unaffected. In family C, four males with intellectual disability, dysmorphic features, and seizures were found to have a nonsense variant. Their mother was not available for testing. In family D, three males with intellectual disability, dysmorphic features, and cerebellar anomalies were found to have a nonsense variant, inherited from an unaffected mother.
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PUBMED:
20528889
Al-Owain et al. (2011) reported a family with four boys and one girl with intellectual disability, seizures, cerebellar hypoplasia, and dysmorphic features with a 68 kb deletion of exons 7-15 of OPHN1. The girl had random X-inactivation. This deletion was inherited from an unaffected mother, but X-inactivation studies were not done for her. This paper also provides a review of all previous cases.
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PUBMED:
24817631
Mignon-Ravix et al. (2014) reported a 4 kb deletion of exons 13–15 of OPHN1, causing a frameshift with a loss of 58 amino acids (pI370_F427delfsX24), in a male patient with global developmental delay and facial dysmorphism. Cerebral MRI showed cerebellar vermis hypoplasia with moderately dilated ventricles. Both parents were mildly disabled. Family history showed that the maternal grandmother had two half-brothers with intellectual disability. This study also revealed a deletion of MAP7D3 on Xq26.3, considered a potential candidate for intellectual disability. Paternal DNA was not available for study.
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PUBMED:
24105372
Santos-Reboucas et al. (2014) described a three-generation Brazilian XLID family co-segregating a novel 21 kb intragenic deletion of OPHN1, resulting in-frame loss of exon 7 at the transcription level. This deletion was predicted to abolish 37 amino acids from the highly conserved N-terminal BAR domain of OPHN1. The affected males had intellectual disability and facial dysmorphism. Cranial MRI scans showed large lateral ventricles, vermis hypoplasia, and cystic dilatation of the cisterna magna in all affected males.
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PUBMED:
30534410
Iida et al. (2019) reported a 13.5 kb maternally inherited deletion in OPHN1 ranging from exon 11-15 in a male patient with developmental delay. Brain CT and brain MRI suggested Dandy-Walker malformation (DWM). His maternal uncle was also affected with hydrocephalus,
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PUBMED:
32872024
Boglis et al. (2020) detected a deletion of exon 21 of OPHN1 in a large family with several affected males (Family pedigree is shown in Figure 1), The clinical phenotype included mild developmental delay, behavioral disturbances, facial dysmorphism, pes planus, nystagmus, strabismus, epilepsy, and occipital arachnoid cyst.
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
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PUBMED: 18512229
Bedeschi et al. (2008) reported a male with an 800 kb duplication of OPHN1 and two other genes (YIPF6 & STARD8) inherited from his normal mother, who had skewed X-inactivation. The patient’s clinical features included intellectual disability, motor delays, seizures, scoliosis, asymmetry, and dysmorphic features that differed from those seen in patients with loss of function variants in OPHN1. A subsequent pregnancy was terminated at 21-week gestation due to hydrocephaly and cerebellar hypoplasia, but this duplication was not detected in that fetus.
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PUBMED: 22659343
Isrie et al. (2012) detected a 790 kb duplication of Xq12 encompassing OPHN1, AR, and YIPF1 in a patient with intellectual disability and dysmorphic features.
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PUBMED: 28931914
Chen et al. (2017) identified a 485 kb duplication of Xq12 involving OPHN1, YIPF1, and STARD8 in a patient with autism spectrum disorder.
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.