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Carpenter
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rankgenesymboltitlescore% reported diseases & mutationsvariants
1 RAB23RAB23, member RAS oncogene
family
0.5100%known disease mutation
germline, loss of function, autosomal recessive, loss of function
6:57059568C>G homo DM  IGV 999x
V161L
rs1060505026 not in ExAC or 1000G.
2 PRIM2DNA primase subunit 20.0 0% 6:57398201T>C homo   IGV 999x
C302R
rs62398997 homcarriers
1000G--
ExAC832775

6:57398226T>G homo   IGV 999x
V310G
rs77436138 homcarriers
1000G--
ExAC132768

3 TRAM2translocation associated
membrane protein 2
0.0 0% 6:52370454C>G homo   IGV 999x
R273P
rs776994347 homcarriers
1000G--
ExAC0522

4 LRRC1leucine rich repeat containing
1
0.0 0% 6:53778661T>G homo   IGV 999x
C334G
rs201915048 homcarriers
1000G--
ExAC0554

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genesymbol var_number chromosome position prediction model clinvar aae protein_features splicing splice_site prematurestop homozygous comphet_aae ref alt coverage transcript_stable
"RAB23""63912134""6""57059568""1""2""1""V161L""""0""""0""1""""C""G""999""ENST00000468148"
"RAB23""63912134""6""57059568""1""2""1""V161L""""0""""0""1""""C""G""999""ENST00000317483"
"PRIM2""8627""6""57398201""3""2""""C302R""""0""""0""1""1""T""C""999""ENST00000607273"
"PRIM2""62868""6""57398226""3""2""""V310G""""0""""0""1""1""T""G""999""ENST00000607273"
"TRAM2""62768""6""52370454""3""2""""R273P""""0""""0""1""""C""G""999""ENST00000182527"
"LRRC1""62816""6""53778661""3""2""""C334G""""0""""0""1""""T""G""999""ENST00000370888"

genesymbol type description chr. startpos endpos synonyms
RAB23 #1 protein-coding 6 57053581 57087078 HSPC137, MGC8900, DKFZp781H0695
  reported mutations germline, loss of function, autosomal recessive, loss of function
  overall score   0.5 100%
  ClinVar 0.5
  links NCBI   ENSEMBL  SwissProt  GeneCards   STRING    PubMed  PubMed+phenotype
  KEGG pathways Hedgehog signaling pathway
  Reactome pathways RGGT:CHM binds RABs, RGGT geranylgeranylates RAB proteins
  WikiPathways Genes related to primary cilium development (based on CRISPR), Ciliopathies
  PFAM Elongation factor Tu GTP binding domain, arf; , ras; , Gtr1/RagA G protein conserved region, Miro-like protein
  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
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  OMIM
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CARPENTER SYNDROME 1 (CRPT1)   phenotype (molecular basis known)   201000
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).



RAS-ASSOCIATED PROTEIN RAB23 (RAB23)   gene description   606144
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 AF
161486) 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.


  OrphaNet Carpenter syndrome   
Age of onset: Neonatal; Antenatal; Childhood
Known mutations: germline, loss of function, autosomal recessive, loss of function (assessed)
  generifs
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  • Rab23 is overexpressed and/or activated in hepatocellular carcinoma (HCC). Rab23 may be both a HCC predictor and a target for treating HCC.
  • RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development.
  • Data show that RAB23 participates in central nervous system development.
  • RAB23 amplifications are associated with gastric cancer
  • A RAB23 mutation (c.86dupA) present in the homozygote state in four relatives of Comorian origin with Carpenter syndrome, is reported.
  • Carpenter syndrome: extended RAB23 mutation spectrum and analysis of nonsense-mediated mRNA decay
  • association of the 6p12.1 locus with sarcoidosis implicates this locus as a further susceptibility factor and RAB23 as a potential signalling component
  • Rab23 directly associates with Su(Fu) and inhibits Gli1 function in a Su(Fu)-dependent manner.
  • Rab9A and Rab23 GTPases play crucial roles in autophagy of Group A Streptococcus.
  • The inhibition of the Rab23 cycle decreases the expression and nuclear localization of Gli1.
  • Rab23 expression level was the highest in Bcap-37 cells.
  • Rab23 was a target gene of miR-367, and ectopic expression of Rab23 could reverse the invasion and migration inhibitory activity of miR-367.
  • Data indicate the essential role of GTP binding protein RAB 23 (Rab23) in pancreatic ductal adenocarcinoma (PDAC) inva-sion, motility and metastasis.
  • Rab23 is expressed in breast cancer cells, and ectopic expression of Rab23 inhibits the growth and proliferation as well as induces cell apoptosis in breast cancer cells These effects may be due to the inhibition by Rab23 of Gli1 and Gli2 mRNA expression
  • Rab23 enhance squamous cell carcinoma cell invasion via up-regulating Rac1.
  • High Rab23 expression is associated with bladder cancer.
  • Rab23 serves as an important oncoprotein in human astrocytoma by regulating cell invasion and migration through Rac1 activity
  • Forced expression of MiR-92b decreased the mRNA and protein level of RAB23, and RAB23 rescued the biological functions of miR-92b. Taken together, this study revealed the oncogenic roles and the regulation of RAB23 in esophageal squamous cell carcino [...]
  • Down-regulation of Rab23 suppressed the proliferation, migration and invasion of prostate cancer cells.
  • miR-429 was down-regulated in hepatocellular carcinoma (HCC) tissues and cells. Up regulation of miR-429 decreased the migratory capacity and reversed the EMT to MET in HCC cells. RAB23 was confirmed as a target of miR-429.
  • Genetic variants in RAB23 and ANXA11 genes were associated with an increased risk of sarcoidosis-associated uveitis.
  • miR-16 acts as a tumor repressor in osteosarcoma cells by reducing epithelial mesenchymal transition, migration and invasion by targeting RAB23 expression.
  • RAB family small GTP binding protein RAB 23 (Rab23) and ADP-ribosylation factor-like 13B (Arl13b) have been implicated in ciliopathy-associated human diseases and could regulate hedgehog proteins (Hh) signalling cascade in multifaceted manners [Review].
  • This is the first report that HE4 can regulate the expression of the Rab23 protein, and that knockdown of RAB23 decreases the proliferation, invasion, and migration abilities as well as inhibits the epithelial-mesenchymal transition process in ovaria [...]
  • OSER1-AS1 acted as a ceRNA to sponge miR-372-3p, thereby positively regulating the Rab23 expression and ultimately acting as a tumor suppressor gene in hepatocellular carcinoma progression
  MGD
  transcripts ENST00000317483: 2986 bases (protein_coding)
ENST00000468148: 1530 bases (protein_coding)
  interactions (STRING)
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  GeneOntology
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PRIM2 #2 protein-coding 6 57182415 57512702 MGC75142, PRIM2, p58, PRIM2A
  reported mutations none
  overall score   0.0 0%
  links NCBI   ENSEMBL  GeneCards   STRING    PubMed  PubMed+phenotype
  KEGG pathways Purine metabolism, Pyrimidine metabolism, Metabolic pathways, DNA replication
  Reactome pathways The primase component of DNA polymerase:primase synthesizes a 6-10 nucleotide RNA primer at the origin, DNA polymerase alpha:primase binds at the origin, The polymerase component of DNA polymerase alpha:primase synthesizes a 20-nucleotide primer at the origin, RFC binding displaces Pol Alpha, Loading of PCNA - Sliding Clamp Formation, RFC dissociates after sliding clamp formation, Formation of Processive Complex, Formation of Okazaki fragments, Formation of the Flap Intermediate, RPA binds to the Flap, Recruitment of Dna2 endonuclease, Removal of RNA primer and dissociation of RPA and Dna2, Removal of remaining Flap, Detection of damage during initiation of DNA synthesis in S-phase, The primase component of DNA polymerase:primase synthesizes a 6-10 nucleotide RNA primer on the G strand of the telomere, The polymerase component of DNA polymerase alpha:primase synthesizes a 20-nucleotide primer on the G strand of the telomere, RFC binding displaces Pol Alpha on the C-strand of the telomere, DNA polymerase:primase binds G-strand of the telomere, Decitabine triphosphate incorporates into DNA
  WikiPathways G1 to S cell cycle control, DNA replication, Pyrimidine metabolism
  PFAM Eukaryotic and archaeal DNA primase, large subunit
  InterPro domains DNA primase large subunit, eukaryotic/archaeal
  OMIM
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PRIMASE POLYPEPTIDE 2A (PRIM2A)   gene description   176636
text:

DESCRIPTION
DNA replication in human cells is initiated by a complex apparatus containing a DNA polymerase-alpha/primase complex that is well conserved from yeast to human. The DNA polymerase-alpha/primase complex contains 4 subunits: the polymerase-alpha p180 (POLA; 312040) and p68 (POLA2) subunits, and the primase p58 (PRIM2A) and p49 (PRIM1; 176635) subunits. Primase synthesizes oligoribonucleotides that serve as primers for the initiation of DNA synthesis. It plays a role in both the initiation of DNA replication and the synthesis of Okazaki fragments for lagging strand synthesis (Shiratori et al., 1995). CLONING By RT-PCR of embryonic kidney cell line RNA using degenerate primers based on mouse and yeast primase subunits, followed by 5-prime RACE, Stadlbauer et al. (1994) cloned the primase p58 subunit. The deduced 446-amino acid protein shares 89% identity with mouse p58, with 5 regions of homology distributed over the central part of the protein. The N and C termini are less well conserved.
GENE FUNCTION
Stadlbauer et al. (1994) demonstrated that mouse and human p58 showed no primase activity in the absence of p48. Zerbe and Kuchta (2002) found that deletion of met288 to leu313 within the polymerase-beta (174760)-like domain of human p58 resulted in a protein that bound to the primase p49 subunit but was unable to support primer synthesis on any template when assays contained only Mg(2+). Including Mn(2+), a metal that stimulates initiation of primer synthesis, allowed the p49/p58 primase complex to synthesize primers at a rate only moderately lower than that of the wildtype enzyme on templates consisting only of deoxycytidylates. By point mutagenesis, Zerbe and Kuchta (2002) determined that arg302, arg306, and lys314 were required for both primer initiation and translocation. Conversion of these residues to alanine interfered with initiation and significantly decreased the processivity of primase. Zerbe and Kuchta (2002) concluded that the polymerase-beta-like region of p58 is important for primer initiation, translocation, and counting. MAPPING By PCR amplification using DNAs from a panel of somatic cell hybrids, Shiratori et al. (1995) mapped the PRIM1 gene and the PRIM2 gene to chromosomes 1 and 6, respectively. By fluorescence in situ hybridization using several genomic DNA probes, they mapped the PRIM1 gene to 1q44 and two PRIM2 loci (PRIM2A and PRIM2B) to 6p12-p11.1. In an erratum to Shiratori et al. (1995), the authors stated that the gene on 1q44 was in fact a processed PRIM1 pseudogene (PRIM1P). The PRIM2B locus identified by Shiratori et al. (1995) may also be a pseudogene (Scott, 2004).


  generifs
  • analysis of the iron-sulfur cluster in the C-terminal domain of the p58 subunit of human DNA primase
  • Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
  • p58C(C-terminal regulatory domain of the large subunit) structure reveals a novel arrangement of an evolutionarily conserved 4Fe-4S cluster buried deeply within the protein core and is not similar to any known protein structure.
  • The fragment that forms a beta-sheet in the reported structure p58C/3L9Q of the same human primase domain is folded in three alpha-helices in our p58C/3Q36 structure, similarly to yeast primase.
  • PRIM2 gene is not imprinted in the placenta.
  • the N-terminal domain of the large subunit of primase (p58N) directly interacts with the C-terminal domain of the catalytic subunit of polalpha (p180C)
  • Data indicate that the conformational changes in primase are necessary to accomplish the initiation and then elongation of RNA synthesis.
  • Data suggest that PRIM1-p58,C-terminal domain stays bound to initiating NTP and 3prime-overhang DNA during whole cycle of RNA primer synthesis; meanwhile, PRIM1-p49 slides along DNA template toward 5prime-end with PRIM1-p58,N-terminal domain attached.
  • Study results show that although human DNA primase C-terminal domain (p58C) can be stabilized in different conformations in the crystalline state, in solution there is effectively no difference in the structure and functional properties of p58C const [...]
  transcripts ENST00000607273: 2290 bases (protein_coding)
ENST00000389488: 2290 bases (processed_transcript)
ENST00000419977: 2197 bases (retained_intron)
ENST00000370687: 909 bases (processed_transcript)
ENST00000274891: 864 bases (processed_transcript)
ENST00000470638: 486 bases (processed_transcript)
ENST00000490313: 410 bases (processed_transcript)
ENST00000550475: 391 bases (processed_transcript)
  interactions (STRING)
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  GeneOntology
TRAM2 #3 protein-coding 6 52362200 52441862 KIAA0057
  reported mutations none
  overall score   0.0 0%
  links NCBI   ENSEMBL  SwissProt  GeneCards   STRING    PubMed  PubMed+phenotype
  PFAM LAG1;, TRAM1-like protein
  InterPro domains TRAM/LAG1/CLN8 homology domain, TRAM1-like protein, Translocation associated membrane protein
  paralogs TRAM1 (51%), TRAM1L1 (44%)
  OMIM
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TRANSLOCATION-ASSOCIATED MEMBRANE PROTEIN 2 (TRAM2)   gene description   608485
text:

DESCRIPTION
TRAM2 is a component of the translocon, a gated macromolecular channel that controls the posttranslational processing of nascent secretory and membrane proteins at the endoplasmic reticulum (ER) membrane. CLONING By sequencing clones obtained from a size-fractionated myeloid cell line cDNA library, Nomura et al. (1994) cloned TRAM2, which they designated KIAA0057. The 3-prime untranslated region of the transcript contains an Alu repeat. The deduced 370-amino acid protein contains possible transmembrane domains. TRAM2 shares 51.6% identity with human RA-regulated nuclear matrix associated protein, RAMP (602221). Northern blot analysis detected moderate expression in all tissues examined except brain. Using the sequence of KIAA0057 to design primers, Onuchic et al. (1999) amplified TRAM2 from kidney cDNA. TRAM2 shares 68% homology with TRAM1 (605190). Northern blot analysis detected 7.0-kb and 0.8-kb TRAM2 transcripts in fetal lung, liver, and kidney. Only the 0.8-kb transcript was detected in fetal brain. Stefanovic et al.(2004) cloned human and rat TRAM2 by differential display of activated and quiescent hepatic stellate cells. The deduced protein contains 7 putative transmembrane regions and shows the same topology as that predicted for TRAM1, but TRAM2 differs at the C terminus.
GENE FUNCTION
Upon activation, quiescent hepatic stellate cells proliferate, change morphologically into myofibroblasts, and increase their synthesis of extracellular matrix proteins. Stefanovic et al. (2004) demonstrated that both TRAM2 and collagen type I (see 120150) are upregulated in activated rat and human hepatic stellate cells. By yeast 2-hybrid screen and in vitro binding assays, they further found that the C terminus of TRAM2 interacts with SERCA2b (108740), the main Ca(2+) pump in the endoplasmic reticulum of hepatic stellate cells and fibroblasts. TRAM2 also coprecipitated with collagen. Deletion of the C terminus of TRAM2, and pharmacologic inhibitors of SERCA2b, inhibited type I collagen synthesis. In addition, depletion of ER Ca(2+) inhibited the folding of triple helical collagen and increased its intracellular degradation. Stefanovic et al. (2004) proposed that, during activation of hepatic stellate cells, TRAM2 recruits SERCA2b to the translocon, and SERCA2b then couples procollagen synthesis and Ca(2+)-dependent molecular chaperones involved in collagen folding.
GENE STRUCTURE
Onuchic et al. (1999) determined that the TRAM2 gene contains 11 exons and spans 79.6 kb. MAPPING By PCR of a human/rodent hybrid panel, Nomura et al. (1994) mapped the TRAM2 gene to chromosome 6. By genomic sequence analysis, Onuchic et al. (1999) mapped the TRAM2 gene to chromosome 6p21.1-p12 near the PKHD1 (606702) gene.


  generifs
  • TRAM2, as a part of the translocon, is required for the biosynthesis of type I collagen by coupling the activity of SERCA2b with the activity of the translocon
  • Observational study of gene-disease association. (HuGE Navigator)
  • Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
  • results support a role of DAP12 in stabilizing TREM2-CTF, thereby protecting against excessive pro-inflammatory responses.
  MGD
  transcripts ENST00000182527: 6908 bases (protein_coding)
  interactions (STRING)
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  GeneOntology
LRRC1 #4 protein-coding 6 53659778 53788919 FLJ10775, dJ523E19.1, LANO, FLJ11834
  reported mutations none
  overall score   0.0 0%
  links NCBI   ENSEMBL  SwissProt  GeneCards   STRING    PubMed  PubMed+phenotype
  Reactome pathways RND2 binds effectors
  PFAM LRR;
  InterPro domains Leucine-rich repeat, Leucine-rich repeat, typical subtype, Leucine rich repeat 4
  paralogs LRRC8E (17%), LRRC8A (19%), LRRIQ4 (23%), LRRD1 (15%), MFHAS1 (13%), RSU1 (21%), SHOC2 (22%), LOC101927933 (11%), LRRC8D (11%), LRRC8B (13%), SCRIB (20%), ERBIN (15%), LRRC7 (14%), LRRC40 (19%)
  OMIM
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LEUCINE-RICH REPEAT-CONTAINING PROTEIN 1 (LRRC1)   gene description   608195
text:
CLONING By searching an EST database for sequences similar to scribble (607733) and erbin (606944), followed by RACE of breast mRNA, Saito et al. (2001) cloned LRRC1, which they designated LANO. The deduced protein contains 16 leucine-rich repeats and a LAP-specific domain, but no PDZ domain. LRRC1 shares 60%, 42%, and 40% amino acid identity with scribble, rat densin-180, and erbin, respectively. Northern blot analysis detected a 3.5-kb transcript expressed predominantly in placenta, kidney, pancreas, prostate, testis, colon, thyroid, and adrenergic glands. Western blot analysis detected endogenous LRRC1 at an apparent molecular mass of about 62 kD in a human colon epithelial (Caco2) cell line. Immunolocalization and confocal sections of permeabilized Caco2 cells detected LRRC1 expression on the basolateral surface.
GENE FUNCTION
By in vitro and in vivo pull-down assays with transfected Caco2 cells, Saito et al. (2001) demonstrated that LRRC1 and a C-terminal LRRC1 peptide interacted with the PDZ domains of DLG1 (601014) and PSD95 (DLG4; 602887). They found a second pool of LRRC1 in a complex with erbin. MAPPING Saito et al. (2001) stated that the LRRC1 gene maps to chromosome 6p12.3-p12.2.


  generifs
  • LRRC1 contributes to HCC development, and may be a potential target for therapeutic intervention in this disease.
  • Lano/LRRC1-depleted cells secrete increased levels of WNT ligands.
  • Common and specific sets of proteins associated to SCRIB and LANO by MS are identified and an extensive landscape of their associated networks and the first comparative analysis of their respective interactomes are provided
  transcripts ENST00000370888: 3180 bases (protein_coding)
ENST00000487251: 2527 bases (nonsense_mediated_decay)
ENST00000370882: 808 bases (protein_coding)
ENST00000490222: 555 bases (retained_intron)
  interactions (STRING)
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  GeneOntology

4 gene(s) ( ms).


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If you feel that MutationDistiller has helped you in your research, please cite the following publication:

MutationDistiller: user-driven identification of pathogenic DNA variants.
Hombach D, Schuelke M, Knierim E, Ehmke N, Schwarz JM, Fischer-Zirnsak B, Seelow D.
Nucleic Acids Res. 2019 May 20. pii: gkz330. doi: 10.1093/nar/gkz330.

Read the paper

entitylast update (YYYY-MM-DD)
ClinVar2018-08-06
Ensembl transcripts:Genbank2016-08-15
Ensembl:Entrez2019-10-28
Entrez gene RIFS2019-10-28
Entrez gene history2019-10-28
Entrez gene positions2019-10-28
Entrez gene synonyms2019-10-28
Entrez genes2019-10-28
Maestro/Mitopred2016-08-15
OMIM2019-09-10
UCSC IDs2016-08-15