| refine your query |
| genesymbol | type | description | chr. | startpos | endpos | synonyms | |
| RAB23 | protein-coding | RAB23, member RAS oncogene family | 6 | 57053581 | 57087078 | HSPC137, MGC8900, DKFZp781H0695 | |
| links | NCBI ENSEMBL SwissProt GeneCards STRING PubMed create primers for all transcripts | ||||||
| KEGG pathways | Hedgehog signaling pathway | ||||||
| Reactome pathways | RGGT:CHM binds RABs, RGGT geranylgeranylates RAB proteins | ||||||
| PFAM | ras; , Miro-like protein, arf; , Elongation factor Tu GTP binding domain, Gtr1/RagA G protein conserved region | ||||||
| InterPro domains | Small GTPase superfamily, Ran GTPase, Small GTPase superfamily, Rho type, Small GTPase superfamily, Rab type, Small GTP-binding protein domain, Small GTPase superfamily, Ras type, P-loop containing nucleoside triphosphate hydrolase | ||||||
| paralogs | RAN (24%) | ||||||
| HPO | |||||||
| OMIM | CARPENTER SYNDROME 1; CRPT1 synopsis: INHERITANCE: Autosomal recessive GROWTH: [Height]; Short stature (<25th percentile); [Weight]; Obesity HEAD AND NECK: [Head]; Brachycephaly; [Face]; Midface hypoplasia; [Ears]; Low-set ears; Malformed ears; Preauricular pits; Conductive hearing loss; Sensorineural hearing loss; [Eyes]; Epicanthal folds; Corneal opacity; Microcornea; Optic atrophy; Lateral displacement of medial canthi; [Nose]; Flat nasal bridge; [Mouth]; High-arched palate; [Teeth]; Missing teeth; Delayed loss of deciduous teeth; [Neck]; Short muscular neck CARDIOVASCULAR: [Heart]; Atrial septal defect; Ventricular septal defect; Pulmonic stenosis; Tetralogy of Fallot; [Vascular]; Transposition of great vessels; Patent ductus arteriosus ABDOMEN: [External features]; Umbilical hernia; Omphalocele; [Spleen]; Accessory spleens GENITOURINARY: [Internal genitalia, male]; Cryptorchidism; [Kidneys]; Hydronephrosis; [Ureters]; Hydroureter SKELETAL: [Skull]; Craniosynostosis (coronal, sagittal, lambdoid sutures); [Spine]; Pilonidal dimple; Absent coccyx; Spina bifida occulta; Scoliosis; [Pelvis]; Coxa valga; Decreased hip-joint mobility; Flared ilia; [Limbs]; Genu valgum; Lateral displacement of patellae; [Hands]; Brachydactyly; Postaxial polydactyly; Clinodactyly; Syndactyly; Camptodactyly; [Feet]; Preaxial polydactyly; Syndactyly; Metatarsus varus NEUROLOGIC: [Central nervous system]; Variable delay (IQ range 52-104) ENDOCRINE FEATURES: Precocious puberty MOLECULAR BASIS: Caused by mutation in the Ras-associated protein RAB23 gene (RAB23, 606144.0001) text: A number sign (#) is used with this entry because of evidence that Carpenter syndrome is caused by homozygous mutation in the RAB23 gene (606144)on chromosome 6p11. CLINICAL FEATURES Carpenter (1909) described 2 sisters and a brother with acrocephaly, peculiar facies, brachydactyly, and syndactyly in the hands, and preaxial polydactyly and syndactyly of the toes. Temtamy (1966) could find 9 other reported cases and added one. In older patients obesity, mental retardation, and hypogonadism had been noted. In all cases the parents have been normal. Parental consanguinity was suspected in 1 case. The case of acrocephalosyndactyly with foot polydactyly reported by Owen (1952) probably represented Carpenter syndrome, as do the sibs reported by Schonenberg and Scheidhauer (1966). One patient thought to have this condition by Palacios and Schimke (1969) was 49 years old. Eaton et al. (1974) reported affected sibs. Cohen et al. (1987) described 2 affected sibs showing marked intrafamilial variability. This experience and a review of the literature suggested that the Goodman syndrome (201020) and the Summitt syndrome (272350) fall well within the clinical spectrum of the Carpenter syndrome. Gershoni-Baruch (1990) described a brother and sister with rather striking differences in severity. The first born had craniosynostosis of the sagittal suture, normal intelligence, and no abnormalities of the hands and feet. The second born sib had polysyndactyly of hands and feet, normal intelligence, and no craniosynostosis. Gershoni-Baruch (1990) suggested that polysyndactyly is not an absolute requisite for the diagnosis of Carpenter syndrome and that the Summitt and Goodman syndromes are 'within the clinical spectrum' of Carpenter syndrome, as suggested by Cohen et al. (1987). Alessandri et al. (2010) described 4 boys with Carpenter syndrome from a consanguineous Comoros Islands pedigree. All 4 boys presented with acrocephaly and polysyndactyly, but displayed variable severity of craniosynostosis ranging from cloverleaf skull to predominant involvement of the metopic ridge (turricephaly). All of the children also had a combination of brachydactyly with agenesis of the middle phalanges, syndactyly, broad thumbs, and postaxial polydactyly in the hands, with preaxial polydactyly and syndactyly of the toes. Mental development was normal in all; brain imaging showed hydrocephalus in 2 of the 4 boys. Additional features included corneal anomaly in 2, cryptorchidism in 3, umbilical hernia in 1, genu valgum in 2, umbilical hernia in 1, severe kyphoscoliosis in 1, patent ductus arteriosus in 1, and accessory spleen in 1. MAPPING Using homozygosity mapping, Jenkins et al. (2007) found linkage of Carpenter syndrome to chromosome 6p12.1-q12. MOLECULAR GENETICS In 15 independent families with Carpenter syndrome, Jenkins et al. (2007) identified 5 different mutations (4 truncating and 1 missense) in the RAB23 gene (see, e.g., L145X, 606144.0001; 606144.0002), which encodes a member of the RAB guanosine triphosphatase (GTPase) family of vesicle transport proteins and acts as a negative regulator of hedgehog (HH) signaling (see 600725). In 10 patients, the disease was caused by homozygosity for the same L145X mutation that resides on a common haplotype, indicative of a founder effect in patients of northern European descent. In 4 boys with Carpenter syndrome from a consanguineous Comoros Islands pedigree, Alessandri et al. (2010) identified homozygosity for a 1-bp duplication in the RAB23 gene (606144.0003). NOMENCLATURE The designation of Carpenter syndrome as ACPS II is a relict of an earlier classification that made the Noack syndrome ACPS I. It is now agreed by most that Noack syndrome is the same as Pfeiffer syndrome (101600). See report at OMIM's website. RAS-ASSOCIATED PROTEIN RAB23; RAB23 text: DESCRIPTION Rab proteins are small GTPases of the Ras superfamily involved in the regulation of intracellular membrane trafficking. The RAB23 gene encodes an essential negative regulator of the Sonic hedgehog (SHH; 600725) signaling pathway. For additional background information on Rab proteins, see 179508. CLONING By a map-based approach, Eggenschwiler et al. (2001) cloned the gene mutant in the mouse 'open brain 'phenotype (opb; see later) and found that it encodes Rab23, a member of the Rab family of vesicle transport proteins. The human RAB23 gene encodes a 237-amino acid protein. RAB23 is 30 to 35% identical to other mammalian Rab proteins and includes all the canonical motifs required for guanine nucleotide binding, GTP hydrolysis, membrane association, and the conformational switch between the GTP and GDP-bound state. Rab23 is a relatively divergent Rab protein with an unusually long carboxy-terminal tail. In the mouse at embryonic day 10.5, Rab23 RNA was present at low levels in most tissues, and was present at high levels in the spinal cord, somites, limb buds, and cranial mesenchyme. In the spinal cord, Rab23 was expressed at highest levels in the dorsal half of the neural tube, although it was excluded from the roof plate. In the limb bud, it was expressed in the crescent of mesenchymal cells that are capable of responding to Shh signaling. The expression pattern of Rab23 RNA is similar to that of Gli3 (165240), another negative regulator of the Shh signaling pathway. GENE STRUCTURE The RAB23 gene contains 8 exons, and the first 2 exons are noncoding (Alessandri et al., 2010). MAPPING By database searching, Zhang et al. (2000) mapped the RAB23 gene to chromosome 6p11 based on similarity between the RAB23 sequence (GenBank GENBANK AF161486) and previously mapped sequences. GENE FUNCTION Mutations in Shh and opb cause opposing transformations in neural cell fate: Shh mutant embryos lack ventral cell types throughout the spinal cord, whereas opb mutant embryos lack dorsal cell types specifically in the caudal spinal cord. Eggenschwiler et al. (2001) demonstrated that opb acts downstream of Shh. Ventral cell types that are absent in Shh mutants, including the floor plate, are present in Shh-opb double mutants. The organization of ventral cell types in Shh-opb double mutants reveals that Shh-independent mechanisms can pattern the neural tube along its dorsal-ventral axis. Eggenschwiler et al. (2001) concluded that dorsalizing signals activate transcription of Rab23 in order to silence the Shh pathway in dorsal neural cells. MOLECULAR GENETICS Carpenter syndrome (201000) is a pleiotropic disorder with autosomal recessive inheritance, the cardinal features of which include craniosynostosis, polysyndactyly, obesity, and cardiac defects. In 15 independent families with Carpenter syndrome, Jenkins et al. (2007) identified 5 different mutations, including 4 truncating (see, e.g., L145X, 606144.0001; 606144.0002) and 1 missense, in the RAB23 gene. In 10 patients, the disease was caused by homozygosity for the same L145X mutation that resides on a common haplotype, indicative of a founder effect in patients of northern European descent. Nonsense mutations of Rab23 in 'open brain' mice were found to cause recessive embryonic lethality with neural tube defects, suggesting a species difference in the requirement for RAB23 during early development. The discovery of RAB23 mutations in patients with Carpenter syndrome implicated HH signaling in cranial suture biogenesis; this was an unexpected finding given that craniosynostosis is not usually associated with mutations of other HH pathway components. The finding also provides a new molecular target for studies of obesity, which is a consistent feature of Carpenter syndrome. In a consanguineous Comoros Islands pedigree with Carpenter syndrome, Alessandri et al. (2010) identified homozygosity for a 1-bp duplication in the RAB23 gene (606144.0003). ANIMAL MODEL Homozygous 'open brain' (opb) mice die during the second half of gestation, with an open neural tube in the head and spinal cord, abnormal somites, polydactyly, and poorly developed eyes (Gunther et al., 1994). Eggenschwiler et al. (2001) found that the opb mutation arises from the Rab23 gene. The opb1 allele encodes a lys-to-ter mutation at codon 39; the opb2 allele encodes an arg-to-ter mutation at codon 80. These alleles would lack the domains required for guanine nucleotide and Rab effector binding and are therefore null alleles. See report at OMIM's website. |
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| OrphaNet | Carpenter syndrome germline (assessed) | ||||||
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| MGD | |||||||
| transcripts | ENST00000317483: 2986 bases (protein_coding) ENST00000468148: 1530 bases (protein_coding) |
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| interactions (STRING) | |||||||
| GeneOntology |
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| If you feel that GeneDistiller has helped you in your research, please cite the following publication: Seelow D, Schwarz JM, Schuelke M. GeneDistiller--distilling candidate genes from linkage intervals. PLoS ONE. 2008;3(12):e3874. Epub 2008 Dec 5. |
| entity | last update (YYYY-MM-DD) |
| Disease Ontology | 2020-06-29 |
| Ensembl 84 (GRCh73) | 2016-06-14 |
| Ensembl:Entrez | 2021-10-28 |
| Entrez gene history | 2021-10-28 |
| Entrez gene positions | 2021-10-28 |
| Entrez gene RIFS | 2021-10-28 |
| Entrez genes | 2021-10-28 |
| Entrez gene synonyms | 2021-10-28 |
| HPO:Genes | 2015-12-22 |
| HPO:OMIM | 2015-12-22 |
| HPO:OrphaNet | 2015-12-22 |
| Human Phenotype Ontology | 2015-12-22 |
| OMIM | 2015-08-25 |