RAB39B |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- RAB39B (HGNC:16499) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- RAB39B, member RAS oncogene family
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- MRX72, WSN
- Alias symbols
- No aliases found
- %HI
- 21.75(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.83(Read more about gnomAD pLI score)
- LOEUF
- 0.52(Read more about gnomAD LOEUF score)
- Cytoband
- Xq28
- Genomic Coordinates
-
GRCh37/hg19: chrX:154487520-154493776 NCBI Ensembl UCSC GRCh38/hg38: chrX:155258235-155264491 NCBI Ensembl UCSC - MANE Select Transcript
- NM_171998.4 ENST00000369454.4 (Read more about MANE Select)
- Function
- Small GTPases Rab involved in autophagy (PubMed:27103069). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:27103069). May regulate the homeostasis of SNCA/alpha-... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- intellectual disability, X-linked 72 Monarch
-
PUBMED:
20159109
Giannandrea et al., 2010 (AJHG) reported two large families (details below) with X-linked intellectual disability (XLID) segregating with point mutations in the RAB39B gene. These mutations (nonsense and splice-site) are predicted to result in a loss-of-function (immunoblotting of HeLa cells transfected with each mutant cDNA did not detect any mutant protein) and were not seen in 150 adult European male controls. In pedigree of family X, figure 1D, 2 affected in second generation and 4 affected individuals in third generation segregating with intellectual disability (2 carrier females in first two generations). Sequence confirmed for a premature stop codon p.Y7X variant in exon 1 of the canonical transcript In pedigree of family MRX72, fig. 1E, multiple affected individuals (7 males) and carrier females (6, one deceased). Also sequence confirmed for a cryptic 5′ splice donor site variant. Affected individuals reported with intellectual disability as well as autism spectrum disorders and seizures.
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PUBMED:
21076407
Vissers et al., 2010 analyzed 10 trios by WES for sequence variants associated with unexplained ID. A nonsense variant, p.Trp186X (Table 2), was identified in the RAB39B gene in proband of Trio 2 and determined the alteration was de novo.
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PUBMED:
23871722
To assess the clinical relevance of reported mutations in genes that have been implicated in monogenic X-linked intellectual disability (XLID), Piton et al., 2013 examined the prevalence of X chromosome mutations in the general population by studying 10,563 X chromosomes from the National Heart, Lung, and Blood (NHLBI) Exome Sequencing Project and systematically reassessed 106 XLID genes. Based on their scoring criteria, RAB39B was considered to be a confirmed XLID gene. The authors reported two loss of function variants, one a splice site change and the other a nonsense variant, Tyr7* (Supp Table 2) in the large cohort of individuals with XLID. Neither of these two variants are reported in gnomAD.
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.