Full text data of SAR1B
SAR1B
(SARA2, SARB)
[Confidence: low (only semi-automatic identification from reviews)]
GTP-binding protein SAR1b (GTP-binding protein B; GTBPB)
GTP-binding protein SAR1b (GTP-binding protein B; GTBPB)
UniProt
Q9Y6B6
ID SAR1B_HUMAN Reviewed; 198 AA.
AC Q9Y6B6; D3DQA4; Q567T4;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 128.
DE RecName: Full=GTP-binding protein SAR1b;
DE AltName: Full=GTP-binding protein B;
DE Short=GTBPB;
GN Name=SAR1B; Synonyms=SARA2, SARB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pituitary tumor;
RA Song H., Peng Y., Dai M., Huang Q., Mao Y., Zhang Q., Mao M., Fu G.,
RA Luo M., Chen J., Hu R.;
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhou Y., Yu L., Gao J., Zhang P.Z., Wang X.K., Zhao S.Y.;
RT "Cloning of a novel human cDNA homologous to murine GTP-binding
RT protein homologue mRNA.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP VARIANTS CMRD ARG-37; ASN-137 AND ARG-179.
RX PubMed=12692552; DOI=10.1038/ng1145;
RA Jones B., Jones E.L., Bonney S.A., Patel H.N., Mensenkamp A.R.,
RA Eichenbaum-Voline S., Rudling M., Myrdal U., Annesi G., Naik S.,
RA Meadows N., Quattrone A., Islam S.A., Naoumova R.P., Angelin B.,
RA Infante R., Levy E., Roy C.C., Freemont P.S., Scott J.,
RA Shoulders C.C.;
RT "Mutations in a Sar1 GTPase of COPII vesicles are associated with
RT lipid absorption disorders.";
RL Nat. Genet. 34:29-31(2003).
RN [7]
RP INVOLVEMENT IN CMRD BUT NOT IN MSS.
RX PubMed=17309654; DOI=10.1111/j.1399-0004.2007.00759.x;
RA Annesi G., Aguglia U., Tarantino P., Annesi F., De Marco E.V.,
RA Civitelli D., Torroni A., Quattrone A.;
RT "SIL1 and SARA2 mutations in Marinesco-Sjogren and chylomicron
RT retention diseases.";
RL Clin. Genet. 71:288-289(2007).
RN [8]
RP VARIANTS CMRD ASP-11 AND GLY-75.
RX PubMed=19274794; DOI=10.1097/MPG.0b013e318183188f;
RA Treepongkaruna S., Chongviriyaphan N., Suthutvoravut U.,
RA Charoenpipop D., Choubtum L., Wattanasirichaigoon D.;
RT "Novel missense mutations of SAR1B gene in an infant with chylomicron
RT retention disease.";
RL J. Pediatr. Gastroenterol. Nutr. 48:370-373(2009).
CC -!- FUNCTION: Involved in transport from the endoplasmic reticulum to
CC the Golgi apparatus. Activated by the guanine nucleotide exchange
CC factor PREB. Involved in the selection of the protein cargo and
CC the assembly of the COPII coat complex.
CC -!- SUBUNIT: Homodimer. Binds PREB. Part of the COPII coat complex.
CC Binds to the cytoplasmic tails of target proteins in the
CC endoplasmic reticulum (By similarity).
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein (By similarity). Golgi apparatus, Golgi stack
CC membrane; Peripheral membrane protein (By similarity).
CC Note=Associated with the endoplasmic reticulum and Golgi stacks,
CC in particular in the juxta-nuclear Golgi region (By similarity).
CC -!- TISSUE SPECIFICITY: Expressed in many tissues including small
CC intestine, liver, muscle and brain.
CC -!- DISEASE: Chylomicron retention disease (CMRD) [MIM:246700]: An
CC autosomal recessive disorder of severe fat malabsorption
CC associated with failure to thrive in infancy. The condition is
CC characterized by deficiency of fat-soluble vitamins, low blood
CC cholesterol levels, and a selective absence of chylomicrons from
CC blood. Affected individuals accumulate chylomicron-like particles
CC in membrane-bound compartments of enterocytes, which contain large
CC cytosolic lipid droplets. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. SAR1 family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF092130; AAD40372.1; -; mRNA.
DR EMBL; AF087850; AAP97161.1; -; mRNA.
DR EMBL; CH471062; EAW62249.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62250.1; -; Genomic_DNA.
DR EMBL; BC002847; AAH02847.1; -; mRNA.
DR EMBL; BC093034; AAH93034.1; -; mRNA.
DR RefSeq; NP_001028675.1; NM_001033503.2.
DR RefSeq; NP_057187.1; NM_016103.3.
DR UniGene; Hs.432984; -.
DR ProteinModelPortal; Q9Y6B6; -.
DR SMR; Q9Y6B6; 13-198.
DR IntAct; Q9Y6B6; 1.
DR STRING; 9606.ENSP00000282606; -.
DR PhosphoSite; Q9Y6B6; -.
DR DMDM; 14285769; -.
DR PaxDb; Q9Y6B6; -.
DR PeptideAtlas; Q9Y6B6; -.
DR PRIDE; Q9Y6B6; -.
DR DNASU; 51128; -.
DR Ensembl; ENST00000402673; ENSP00000385432; ENSG00000152700.
DR Ensembl; ENST00000439578; ENSP00000404997; ENSG00000152700.
DR GeneID; 51128; -.
DR KEGG; hsa:51128; -.
DR UCSC; uc003kzq.3; human.
DR CTD; 51128; -.
DR GeneCards; GC05M133971; -.
DR HGNC; HGNC:10535; SAR1B.
DR HPA; HPA006923; -.
DR MIM; 246700; phenotype.
DR MIM; 607690; gene.
DR neXtProt; NX_Q9Y6B6; -.
DR Orphanet; 71; Chylomicron retention disease.
DR PharmGKB; PA34943; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000163690; -.
DR HOVERGEN; HBG104997; -.
DR InParanoid; Q9Y6B6; -.
DR KO; K07953; -.
DR OMA; DEQLANC; -.
DR OrthoDB; EOG7W1550; -.
DR PhylomeDB; Q9Y6B6; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_6900; Immune System.
DR GeneWiki; SAR1B; -.
DR GenomeRNAi; 51128; -.
DR NextBio; 53943; -.
DR PRO; PR:Q9Y6B6; -.
DR ArrayExpress; Q9Y6B6; -.
DR Bgee; Q9Y6B6; -.
DR CleanEx; HS_SAR1B; -.
DR Genevestigator; Q9Y6B6; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; TAS:Reactome.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; TAS:Reactome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
DR GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; TAS:Reactome.
DR GO; GO:0048208; P:COPII vesicle coating; TAS:Reactome.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR GO; GO:0018279; P:protein N-linked glycosylation via asparagine; TAS:Reactome.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR006689; Small_GTPase_ARF/SAR.
DR InterPro; IPR006687; Small_GTPase_SAR1.
DR PANTHER; PTHR11711:SF12; PTHR11711:SF12; 1.
DR Pfam; PF00025; Arf; 1.
DR PRINTS; PR00328; SAR1GTPBP.
DR SMART; SM00178; SAR; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51422; SAR1; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Disease mutation; Endoplasmic reticulum;
KW ER-Golgi transport; Golgi apparatus; GTP-binding; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1 198 GTP-binding protein SAR1b.
FT /FTId=PRO_0000206261.
FT NP_BIND 32 39 GTP (By similarity).
FT NP_BIND 75 78 GTP (By similarity).
FT NP_BIND 134 137 GTP (By similarity).
FT METAL 34 34 Magnesium (By similarity).
FT METAL 75 75 Magnesium (By similarity).
FT VARIANT 11 11 G -> D (in CMRD).
FT /FTId=VAR_059051.
FT VARIANT 37 37 G -> R (in CMRD; loss of GDP/GTP-
FT binding).
FT /FTId=VAR_016806.
FT VARIANT 75 75 D -> G (in CMRD).
FT /FTId=VAR_059052.
FT VARIANT 137 137 D -> N (in CMRD; reduced affinity for
FT GDP/GTP; dbSNP:rs28942109).
FT /FTId=VAR_016807.
FT VARIANT 179 179 S -> R (in CMRD; loss of GDP/GTP-binding;
FT dbSNP:rs28942110).
FT /FTId=VAR_016808.
SQ SEQUENCE 198 AA; 22410 MW; 3F567683D7F509E6 CRC64;
MSFIFDWIYS GFSSVLQFLG LYKKTGKLVF LGLDNAGKTT LLHMLKDDRL GQHVPTLHPT
SEELTIAGMT FTTFDLGGHV QARRVWKNYL PAINGIVFLV DCADHERLLE SKEELDSLMT
DETIANVPIL ILGNKIDRPE AISEERLREM FGLYGQTTGK GSISLKELNA RPLEVFMCSV
LKRQGYGEGF RWMAQYID
//
ID SAR1B_HUMAN Reviewed; 198 AA.
AC Q9Y6B6; D3DQA4; Q567T4;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 128.
DE RecName: Full=GTP-binding protein SAR1b;
DE AltName: Full=GTP-binding protein B;
DE Short=GTBPB;
GN Name=SAR1B; Synonyms=SARA2, SARB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pituitary tumor;
RA Song H., Peng Y., Dai M., Huang Q., Mao Y., Zhang Q., Mao M., Fu G.,
RA Luo M., Chen J., Hu R.;
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhou Y., Yu L., Gao J., Zhang P.Z., Wang X.K., Zhao S.Y.;
RT "Cloning of a novel human cDNA homologous to murine GTP-binding
RT protein homologue mRNA.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP VARIANTS CMRD ARG-37; ASN-137 AND ARG-179.
RX PubMed=12692552; DOI=10.1038/ng1145;
RA Jones B., Jones E.L., Bonney S.A., Patel H.N., Mensenkamp A.R.,
RA Eichenbaum-Voline S., Rudling M., Myrdal U., Annesi G., Naik S.,
RA Meadows N., Quattrone A., Islam S.A., Naoumova R.P., Angelin B.,
RA Infante R., Levy E., Roy C.C., Freemont P.S., Scott J.,
RA Shoulders C.C.;
RT "Mutations in a Sar1 GTPase of COPII vesicles are associated with
RT lipid absorption disorders.";
RL Nat. Genet. 34:29-31(2003).
RN [7]
RP INVOLVEMENT IN CMRD BUT NOT IN MSS.
RX PubMed=17309654; DOI=10.1111/j.1399-0004.2007.00759.x;
RA Annesi G., Aguglia U., Tarantino P., Annesi F., De Marco E.V.,
RA Civitelli D., Torroni A., Quattrone A.;
RT "SIL1 and SARA2 mutations in Marinesco-Sjogren and chylomicron
RT retention diseases.";
RL Clin. Genet. 71:288-289(2007).
RN [8]
RP VARIANTS CMRD ASP-11 AND GLY-75.
RX PubMed=19274794; DOI=10.1097/MPG.0b013e318183188f;
RA Treepongkaruna S., Chongviriyaphan N., Suthutvoravut U.,
RA Charoenpipop D., Choubtum L., Wattanasirichaigoon D.;
RT "Novel missense mutations of SAR1B gene in an infant with chylomicron
RT retention disease.";
RL J. Pediatr. Gastroenterol. Nutr. 48:370-373(2009).
CC -!- FUNCTION: Involved in transport from the endoplasmic reticulum to
CC the Golgi apparatus. Activated by the guanine nucleotide exchange
CC factor PREB. Involved in the selection of the protein cargo and
CC the assembly of the COPII coat complex.
CC -!- SUBUNIT: Homodimer. Binds PREB. Part of the COPII coat complex.
CC Binds to the cytoplasmic tails of target proteins in the
CC endoplasmic reticulum (By similarity).
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein (By similarity). Golgi apparatus, Golgi stack
CC membrane; Peripheral membrane protein (By similarity).
CC Note=Associated with the endoplasmic reticulum and Golgi stacks,
CC in particular in the juxta-nuclear Golgi region (By similarity).
CC -!- TISSUE SPECIFICITY: Expressed in many tissues including small
CC intestine, liver, muscle and brain.
CC -!- DISEASE: Chylomicron retention disease (CMRD) [MIM:246700]: An
CC autosomal recessive disorder of severe fat malabsorption
CC associated with failure to thrive in infancy. The condition is
CC characterized by deficiency of fat-soluble vitamins, low blood
CC cholesterol levels, and a selective absence of chylomicrons from
CC blood. Affected individuals accumulate chylomicron-like particles
CC in membrane-bound compartments of enterocytes, which contain large
CC cytosolic lipid droplets. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. SAR1 family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF092130; AAD40372.1; -; mRNA.
DR EMBL; AF087850; AAP97161.1; -; mRNA.
DR EMBL; CH471062; EAW62249.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62250.1; -; Genomic_DNA.
DR EMBL; BC002847; AAH02847.1; -; mRNA.
DR EMBL; BC093034; AAH93034.1; -; mRNA.
DR RefSeq; NP_001028675.1; NM_001033503.2.
DR RefSeq; NP_057187.1; NM_016103.3.
DR UniGene; Hs.432984; -.
DR ProteinModelPortal; Q9Y6B6; -.
DR SMR; Q9Y6B6; 13-198.
DR IntAct; Q9Y6B6; 1.
DR STRING; 9606.ENSP00000282606; -.
DR PhosphoSite; Q9Y6B6; -.
DR DMDM; 14285769; -.
DR PaxDb; Q9Y6B6; -.
DR PeptideAtlas; Q9Y6B6; -.
DR PRIDE; Q9Y6B6; -.
DR DNASU; 51128; -.
DR Ensembl; ENST00000402673; ENSP00000385432; ENSG00000152700.
DR Ensembl; ENST00000439578; ENSP00000404997; ENSG00000152700.
DR GeneID; 51128; -.
DR KEGG; hsa:51128; -.
DR UCSC; uc003kzq.3; human.
DR CTD; 51128; -.
DR GeneCards; GC05M133971; -.
DR HGNC; HGNC:10535; SAR1B.
DR HPA; HPA006923; -.
DR MIM; 246700; phenotype.
DR MIM; 607690; gene.
DR neXtProt; NX_Q9Y6B6; -.
DR Orphanet; 71; Chylomicron retention disease.
DR PharmGKB; PA34943; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000163690; -.
DR HOVERGEN; HBG104997; -.
DR InParanoid; Q9Y6B6; -.
DR KO; K07953; -.
DR OMA; DEQLANC; -.
DR OrthoDB; EOG7W1550; -.
DR PhylomeDB; Q9Y6B6; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_6900; Immune System.
DR GeneWiki; SAR1B; -.
DR GenomeRNAi; 51128; -.
DR NextBio; 53943; -.
DR PRO; PR:Q9Y6B6; -.
DR ArrayExpress; Q9Y6B6; -.
DR Bgee; Q9Y6B6; -.
DR CleanEx; HS_SAR1B; -.
DR Genevestigator; Q9Y6B6; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; TAS:Reactome.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; TAS:Reactome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
DR GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; TAS:Reactome.
DR GO; GO:0048208; P:COPII vesicle coating; TAS:Reactome.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR GO; GO:0018279; P:protein N-linked glycosylation via asparagine; TAS:Reactome.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR006689; Small_GTPase_ARF/SAR.
DR InterPro; IPR006687; Small_GTPase_SAR1.
DR PANTHER; PTHR11711:SF12; PTHR11711:SF12; 1.
DR Pfam; PF00025; Arf; 1.
DR PRINTS; PR00328; SAR1GTPBP.
DR SMART; SM00178; SAR; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51422; SAR1; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Disease mutation; Endoplasmic reticulum;
KW ER-Golgi transport; Golgi apparatus; GTP-binding; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1 198 GTP-binding protein SAR1b.
FT /FTId=PRO_0000206261.
FT NP_BIND 32 39 GTP (By similarity).
FT NP_BIND 75 78 GTP (By similarity).
FT NP_BIND 134 137 GTP (By similarity).
FT METAL 34 34 Magnesium (By similarity).
FT METAL 75 75 Magnesium (By similarity).
FT VARIANT 11 11 G -> D (in CMRD).
FT /FTId=VAR_059051.
FT VARIANT 37 37 G -> R (in CMRD; loss of GDP/GTP-
FT binding).
FT /FTId=VAR_016806.
FT VARIANT 75 75 D -> G (in CMRD).
FT /FTId=VAR_059052.
FT VARIANT 137 137 D -> N (in CMRD; reduced affinity for
FT GDP/GTP; dbSNP:rs28942109).
FT /FTId=VAR_016807.
FT VARIANT 179 179 S -> R (in CMRD; loss of GDP/GTP-binding;
FT dbSNP:rs28942110).
FT /FTId=VAR_016808.
SQ SEQUENCE 198 AA; 22410 MW; 3F567683D7F509E6 CRC64;
MSFIFDWIYS GFSSVLQFLG LYKKTGKLVF LGLDNAGKTT LLHMLKDDRL GQHVPTLHPT
SEELTIAGMT FTTFDLGGHV QARRVWKNYL PAINGIVFLV DCADHERLLE SKEELDSLMT
DETIANVPIL ILGNKIDRPE AISEERLREM FGLYGQTTGK GSISLKELNA RPLEVFMCSV
LKRQGYGEGF RWMAQYID
//
MIM
246700
*RECORD*
*FIELD* NO
246700
*FIELD* TI
#246700 CHYLOMICRON RETENTION DISEASE; CMRD
;;ANDERSON DISEASE; ANDD;;
LIPID TRANSPORT DEFECT OF INTESTINE;;
read moreHYPOBETALIPOPROTEINEMIA WITH ACCUMULATION OF APOLIPOPROTEIN B-LIKE
PROTEIN IN INTESTINAL CELLS
*FIELD* TX
A number sign (#) is used with this entry because chylomicron retention
disease (CMRD), also referred to as Anderson disease, caused by
homozygous or compound heterozygous mutation in the SAR1B gene (607690)
on chromosome 5q31.
DESCRIPTION
Chylomicron retention disease is an autosomal recessive disorder of
severe fat malabsorption associated with failure to thrive in infancy
(Dannoura et al., 1999).
CLINICAL FEATURES
Anderson et al. (1961), Lamy et al. (1967) and Silverberg et al. (1968)
described infants with severe steatorrhea. An intestinal defect in lipid
transport and a failure of chylomicron formation was suggested, similar
to that observed in abetalipoproteinemia (200100). However, neither
acanthocytosis nor neuroocular symptoms occurred in Anderson disease.
Bouma et al. (1986) described 7 cases (3 young adults and 4 children) in
5 kindreds with Anderson disease. Several of the patients were of
Algerian descent. All presented with severe diarrhea in childhood and
had a varying degree of growth retardation. The diagnosis was
established by the finding of fat-laden enterocytes in small bowel
biopsies. The transmission pattern was consistent with autosomal
recessive inheritance. Enterocytes isolated from intestinal biopsies of
patients after an overnight fast show numerous fat droplets, as in
abetalipoproteinemia. Immunoenzymatic staining of enterocytes showed
large amounts of material that reacted with a polyclonal antiserum to
apolipoprotein B (107730) and a monoclonal antibody to B48.
Roy et al. (1987) and Kane and Havel (1989) described chylomicron
retention disease. Roy et al. (1987) reported 8 affected infants and
distinguished the disorder from abetalipoproteinemia. One of the
patients had mild acanthocytosis and 3 patients in their teens had mild
peripheral neuropathy with diminished or absent deep tendon reflexes and
diminished vibratory sense, and definite or borderline mental
retardation. All showed severe growth retardation, steatorrhea, and
malnutrition with hypoalbuminemia in 3 and undetectably low plasma
vitamin E levels in 5. Although none had retinitis pigmentosa, some
showed mild defects in color vision.
Nemeth et al. (1995) described 2 sibs with fat malabsorption and jejunal
chylomicron retention. Plasma lipoproteins were studied in the patients
and their first-degree Relatives. The patients were a 14-year-old girl
and her 8-year-old brother. Compared to healthy controls, they both had
low fasting plasma concentrations of plasma total, HDL, and LDL
cholesterol, as well as of apolipoproteins A-I (107680) and B. No
increase in plasma lipoprotein levels or detectable apo B-48 was
observed following an oral fat load. Histologic studies of jejunal
biopsy specimens obtained during fasting and 1 hour postprandially
showed severe steatosis, and an apparent block of chylomicron secretion
from the endoplasmic reticulum into the Golgi apparatus was observed by
electron microscopy. Liver biopsy specimens showed moderate steatosis
and ultrastructural changes similar to those in the enterocytes. One
healthy sister had a normal plasma lipoprotein pattern, and showed
increased plasma triglyceride levels as well as the presence of apo B-48
following an oral fat load. Both parents had normal plasma total
cholesterol levels, but clearly reduced fasting concentrations of HDL
cholesterol and apo A-I. Nemeth et al. (1995) suggested that at least in
this family, determination of plasma apo A-I levels might thus prove
useful in the identification of heterozygotes.
- Clinical Variability
Aguglia et al. (2000) described 2 Italian brothers, aged 19 and 12
years, who presented with a clinical diagnosis of Marinesco-Sjogren
syndrome (MSS; 248800). They also had very low serum vitamin E
concentrations and an absence of postprandial chylomicrons. Ataxia with
isolated vitamin E deficiency (277460), abetalipoproteinemia, and
hypobetalipoproteinemia (605019) were ruled out. Findings on electron
microscopy of the intestinal mucosa were consistent with chylomicron
retention disease. Aguglia et al. (2000) postulated that both CMRD and
MSS were related to defects in a gene crucial for the assembly or
secretion of chylomicron particles. In the brothers reported by Aguglia
et al. (2000), Jones et al. (2003) identified a mutation in the SAR1B
gene (607690.0006), responsible for CMRD, and Annesi et al. (2007)
identified a mutation in the SIL1 gene (608005.0004), responsible for
MSS. The findings indicated that the patients had 2 distinct diseases
due to mutations in 2 different genes, rather than defects in a single
gene leading to both disorders.
OTHER FEATURES
Silvain et al. (2008) reported increased serum creatine kinase in 8 CMRD
patients between the ages of 13 and 39 years. Two patients had mild
clinical symptoms suggestive of mechanical muscle irritability, but none
had frank muscle weakness. A 38-year-old woman had increased CK-MB, but
no evidence of cardiac dysfunction. A 35-year-old woman had normal serum
CK-MB, but decreased cardiac ejection fraction.
INHERITANCE
Lamy et al. (1967) reported 2 affected brothers, and Silverberg et al.
(1968) noted parental consanguinity, both suggesting autosomal recessive
inheritance.
PATHOGENESIS
By in vitro studies of small intestinal explants from CMRD patients,
Levy et al. (1987) found normal apoB-48 protein synthesis, but deficient
glycosylation. The authors postulated a defect in the formation and
secretion of chylomicrons resulting from a defect in glycosylation.
Dannoura et al. (1999) studied 8 patients with Anderson disease from 7
unrelated families of North African origin after treatment with a
low-fat diet. Lipid loading of intestinal biopsies persisted, but the
pattern and the extent of loading varied among the patients. Electron
microscopy showed lipoprotein-like particles in membrane-bound
compartments, the densities and mean diameters of which were, in
general, significantly larger than in normal-fed subjects. There were
also large lipid particles with diameters up to 7,043 nm that were not
surrounded by a membrane. Rarely, lipoprotein-like particles were
observed in the intercellular spaces. All of these changes could be seen
in all patients. Intestinal organ cultures showed that apolipoprotein B
and apolipoprotein A-IV (APOA4; 107690) were synthesized with apparently
normal molecular masses and that small amounts were secreted in
lipid-bound forms. Normal microsomal triglyceride transfer protein (MTP;
157147) and activity were also detected in intestinal biopsies.
Segregation analyses of 4 families excluded involvement of significant
regions of the genome surrounding the genes encoding the apolipoproteins
expressed in the intestine, as well as the genes encoding 3
intracellular lipid transport proteins, MTP, FABP1 (134650), and FABPZ
(134640). The results suggested that factors other than apolipoproteins
and MTP are important for human intestinal chylomicron assembly and
secretion.
Duden (2003) noted that although endoplasmic reticulum-to-Golgi
trafficking has been well characterized by both genetic and biochemical
methods, few human disorders have been attributed to defects in its
individual components. It is likely that the functional redundancy of
the COPII pathway leads to nonlethal phenotypes that have escaped
classification. Three disorders due to defects in this system are CMRD
disease, X-linked spondyloepiphyseal dysplasia tarda (313400), and
combined deficiency of clotting factors V and VIII (277300).
MOLECULAR GENETICS
- Mutations in the SAR1B Gene
Jones et al. (2003) identified a region of apparent homozygosity on
chromosome 5q31.1 that segregated with affected status in 4 families
with CMRD. In 10 affected individuals from 7 families with chylomicron
retention disease, Jones et al. (2003) identified homozygous or compound
heterozygous mutations in the SAR1B gene (see, e.g.,
607690.0001-607690.0005). Several of the patients had previously been
reported (Bouma et al., 1986), Roy et al. (1987), Nemeth et al. (1995),
and Dannoura et al. (1999).
- Exclusion Studies
Pessah et al. (1991) provided clear genetic evidence that Anderson
disease is not due to a defect in the APOB gene: RFLP studies in 2
families indicated that affected children inherited different APOB
alleles from at least 1 parent. Strich et al. (1993) arrived at the same
conclusion from study of a family in which 3 of 7 children with
consanguineous parents were affected. All 3 suffered from diarrhea,
failure to thrive, and recurrent infections during infancy. Although the
symptoms disappeared later in life, biochemical disorders (e.g., low
plasma levels of apolipoproteins A1 (107680) and B as well as
cholesterol, resulting in avitaminosis E, plus failure to secrete
chylomicrons after a fat meal) persisted. Electron microscopy of
enterocytes in 1 of the patients showed accumulation of lipid vacuoles.
A VNTR polymorphism linked to the APOB locus excluded that gene as the
site of the mutation.
*FIELD* RF
1. Aguglia, U.; Annesi, G.; Pasquinelli, G.; Spadafora, P.; Gambardella,
A.; Annesi, F.; Pasqua, A. A.; Cavalcanti, F.; Crescibene, L.; Bagala,
A.; Bono, F.; Oliveri, R. L.; Valentino, P.; Zappia, M.; Quattrone,
A.: Vitamin E deficiency due to chylomicron retention disease in
Marinesco-Sjogren syndrome. Ann. Neurol. 47: 260-264, 2000.
2. Anderson, C. M.; Townley, R. R. W.; Freeman, M.; Johansen, P.:
Unusual causes of steatorrhoea in infancy and childhood. Med. J.
Aust. 2: 617-622, 1961.
3. Annesi, G.; Aguglia, U.; Tarantino, P.; Annesi, F.; De Marco, E.
V.; Civitelli, D.; Torroni, A.; Quattrone, A.: SIL1 and SARA2 mutations
in Marinesco-Sjogren and chylomicron retention disease. (Letter) Clin.
Genet. 71: 288-289, 2007.
4. Bouma, M.-E.; Beucler, I.; Aggerbeck, L.-P.; Infante, R.; Schmitz,
J.: Hypobetalipoproteinemia with accumulation of an apoprotein B-like
protein in intestinal cells: immunoenzymatic and biochemical characterization
of seven cases of Anderson's disease. J. Clin. Invest. 78: 398-410,
1986.
5. Dannoura, A. H.; Berriot-Varoqueaux, N.; Amati, P.; Abadie, V.;
Verthier, N.; Schmitz, J.; Wetterau, J. R.; Samson-Bouma, M.-E.; Aggerbeck,
L. P.: Anderson's disease: exclusion of apolipoprotein and intracellular
lipid transport genes. Arterioscler. Thromb. Vasc. Biol. 19: 2494-2508,
1999.
6. Duden, R.: ER-to-Golgi transport: COPI and COPII function (review). Molec.
Membr. Biol. 20: 197-207, 2003.
7. Jones, B.; Jones, E. L.; Bonney, S. A.; Patel, H. N.; Mensenkamp,
A. R.; Eichenbaum-Voline, S.; Rudling, M.; Myrdal, U.; Annesi, G.;
Naik, S.; Meadows, N.; Quattrone, A.; and 9 others: Mutations in
a Sar1 GTPase of COPII vesicles are associated with lipid absorption
disorders. Nature Genet. 34: 29-31, 2003.
8. Kane, J. P.; Havel, R. J.: Disorders of the biogenesis and secretion
of lipoproteins containing the B apolipoproteins.In: Scriver, C. R.;
Beaudet, A. L.; Sly, W. S.; Valle, D.: The Metabolic Basis of Inherited
Disease. New York: McGraw-Hill (pub.) (6th ed.) I: 1989. Pp.
1154-1155.
9. Lamy, M.; Frezal, J.; Rey, J.; Jos, J.; Nezelof, C.; Herrault,
A.; Cohen-Solal, J.: Diarrhee chronique par trouble du transfert
intra-cellulaire des lipides. Arch. Franc. Pediat. 24: 1079 only,
1967.
10. Levy, E.; Marcel, Y.; Deckelbaum, R. J.; Milne, R.; Lepage, G.;
Seidman, E.; Bendayan, M.; Roy, C. C.: Intestinal apoB synthesis,
lipids and lipoproteins in chylomicron retention disease. J. Lipid
Res. 28: 1263-1274, 1987. Note: Erratum: J. Lipid. Res.: 29: 119
only, 1988.
11. Nemeth, A.; Myrdal, U.; veress, B.; Rudling, M.; Berglund, L.;
Angelin, B.: Studies on lipoprotein metabolism in a family with jejunal
chylomicron retention. Europ. J. Clin. Invest. 25: 271-280, 1995.
12. Pessah, M.; Benlian, P.; Beucler, I.; Loux, N.; Schmitz, J.; Junien,
C.; Infante, R.: Anderson's disease: genetic exclusion of the apolipoprotein-B
gene in two families. J. Clin. Invest. 87: 367-370, 1991.
13. Roy, C. C.; Levy, E.; Green, P. H. R.; Sniderman, A.; Letarte,
J.; Buts, J. P.; Orquin, J.; Brochu, P.; Weber, A. M.; Morin, C. L.;
Marcel, Y.; Deckelbaum, R. J.: Malabsorption, hypocholesterolemia,
and fat-filled enterocytes with increased intestinal apoprotein B:
chylomicron retention disease. Gastroenterology 92: 390-399, 1987.
14. Silvain, M.; Bligny, D.; Aparicio, T.; Laforet, P.; Grodet, A.;
Peretti, N.; Menard, D.; Djouadi, F.; Jardel, C.; Begue, J. M.; Walker,
F.; Schmitz, J.; Lachaux, A.; Aggerbeck, L. P.; Samson-Bouma, M. E.
: Anderson's disease (chylomicron retention disease): a new mutation
in the SARA2 gene associated with muscular and cardiac abnormalities. Clin.
Genet. 74: 546-552, 2008.
15. Silverberg, M.; Kessler, J.; Neumann, P. Z.; Wiglesworth, F. W.
: An intestinal lipid transport defect. A possible variant of hypo-beta-lipoproteinemia.
(Abstract) Gastroenterology 54: 1271-1272, 1968.
16. Strich, D.; Goldstein, R.; Phillips, A.; Shemer, R.; Goldberg,
Y.; Razin, A.; Freier, S.: Anderson's disease: no linkage to the
apo B locus. J. Pediat. Gastroent. Nutr. 16: 257-264, 1993.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Other];
Failure to thrive;
Growth retardation
ABDOMEN:
[Gastrointestinal];
Fat malabsorption;
Severe diarrhea;
Steatorrhea;
Malnutrition;
Vomiting;
Jejunal endoscopy shows white epithelium;
Small bowel enterocytes accumulate lipid droplets in membrane-bound
compartments or in the cytoplasm
NEUROLOGIC:
[Peripheral nervous system];
Neurologic deficits may occur secondarily to malabsorption;
Peripheral neuropathy;
Diminished or absent deep tendon reflexes;
Diminished vibratory sense
LABORATORY ABNORMALITIES:
Hypocholesterolemia;
Deficiency of fat-soluble vitamins;
Normal serum triglycerides;
Absence of chylomicrons in lymph and plasma;
Defect in chylomicron secretion;
Hypobetalipoproteinemia
MISCELLANEOUS:
Onset in infancy
MOLECULAR BASIS:
Caused by mutation in the SAR1, S. cerevisiae, homolog B gene (SAR1B,
607690.0001)
*FIELD* CN
Cassandra L. Kniffin - revised: 2/23/2009
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
joanna: 05/14/2009
ckniffin: 2/23/2009
alopez: 4/15/2003
*FIELD* CN
Cassandra L. Kniffin - updated: 2/23/2009
Cassandra L. Kniffin - updated: 8/29/2007
Victor A. McKusick - updated: 10/26/2006
Victor A. McKusick - updated: 4/14/2003
Victor A. McKusick - updated: 3/9/2001
Victor A. McKusick - updated: 1/19/2000
*FIELD* CD
Victor A. McKusick: 6/3/1986
*FIELD* ED
carol: 12/04/2013
wwang: 5/23/2011
wwang: 4/2/2009
ckniffin: 2/23/2009
carol: 1/26/2009
wwang: 9/11/2007
ckniffin: 8/29/2007
alopez: 11/1/2006
terry: 10/26/2006
alopez: 3/17/2004
alopez: 4/30/2003
alopez: 4/15/2003
terry: 4/14/2003
cwells: 3/30/2001
terry: 3/9/2001
mcapotos: 1/27/2000
mcapotos: 1/20/2000
terry: 1/19/2000
davew: 8/19/1994
mimadm: 4/14/1994
warfield: 3/30/1994
carol: 6/3/1993
supermim: 3/17/1992
carol: 1/24/1991
*RECORD*
*FIELD* NO
246700
*FIELD* TI
#246700 CHYLOMICRON RETENTION DISEASE; CMRD
;;ANDERSON DISEASE; ANDD;;
LIPID TRANSPORT DEFECT OF INTESTINE;;
read moreHYPOBETALIPOPROTEINEMIA WITH ACCUMULATION OF APOLIPOPROTEIN B-LIKE
PROTEIN IN INTESTINAL CELLS
*FIELD* TX
A number sign (#) is used with this entry because chylomicron retention
disease (CMRD), also referred to as Anderson disease, caused by
homozygous or compound heterozygous mutation in the SAR1B gene (607690)
on chromosome 5q31.
DESCRIPTION
Chylomicron retention disease is an autosomal recessive disorder of
severe fat malabsorption associated with failure to thrive in infancy
(Dannoura et al., 1999).
CLINICAL FEATURES
Anderson et al. (1961), Lamy et al. (1967) and Silverberg et al. (1968)
described infants with severe steatorrhea. An intestinal defect in lipid
transport and a failure of chylomicron formation was suggested, similar
to that observed in abetalipoproteinemia (200100). However, neither
acanthocytosis nor neuroocular symptoms occurred in Anderson disease.
Bouma et al. (1986) described 7 cases (3 young adults and 4 children) in
5 kindreds with Anderson disease. Several of the patients were of
Algerian descent. All presented with severe diarrhea in childhood and
had a varying degree of growth retardation. The diagnosis was
established by the finding of fat-laden enterocytes in small bowel
biopsies. The transmission pattern was consistent with autosomal
recessive inheritance. Enterocytes isolated from intestinal biopsies of
patients after an overnight fast show numerous fat droplets, as in
abetalipoproteinemia. Immunoenzymatic staining of enterocytes showed
large amounts of material that reacted with a polyclonal antiserum to
apolipoprotein B (107730) and a monoclonal antibody to B48.
Roy et al. (1987) and Kane and Havel (1989) described chylomicron
retention disease. Roy et al. (1987) reported 8 affected infants and
distinguished the disorder from abetalipoproteinemia. One of the
patients had mild acanthocytosis and 3 patients in their teens had mild
peripheral neuropathy with diminished or absent deep tendon reflexes and
diminished vibratory sense, and definite or borderline mental
retardation. All showed severe growth retardation, steatorrhea, and
malnutrition with hypoalbuminemia in 3 and undetectably low plasma
vitamin E levels in 5. Although none had retinitis pigmentosa, some
showed mild defects in color vision.
Nemeth et al. (1995) described 2 sibs with fat malabsorption and jejunal
chylomicron retention. Plasma lipoproteins were studied in the patients
and their first-degree Relatives. The patients were a 14-year-old girl
and her 8-year-old brother. Compared to healthy controls, they both had
low fasting plasma concentrations of plasma total, HDL, and LDL
cholesterol, as well as of apolipoproteins A-I (107680) and B. No
increase in plasma lipoprotein levels or detectable apo B-48 was
observed following an oral fat load. Histologic studies of jejunal
biopsy specimens obtained during fasting and 1 hour postprandially
showed severe steatosis, and an apparent block of chylomicron secretion
from the endoplasmic reticulum into the Golgi apparatus was observed by
electron microscopy. Liver biopsy specimens showed moderate steatosis
and ultrastructural changes similar to those in the enterocytes. One
healthy sister had a normal plasma lipoprotein pattern, and showed
increased plasma triglyceride levels as well as the presence of apo B-48
following an oral fat load. Both parents had normal plasma total
cholesterol levels, but clearly reduced fasting concentrations of HDL
cholesterol and apo A-I. Nemeth et al. (1995) suggested that at least in
this family, determination of plasma apo A-I levels might thus prove
useful in the identification of heterozygotes.
- Clinical Variability
Aguglia et al. (2000) described 2 Italian brothers, aged 19 and 12
years, who presented with a clinical diagnosis of Marinesco-Sjogren
syndrome (MSS; 248800). They also had very low serum vitamin E
concentrations and an absence of postprandial chylomicrons. Ataxia with
isolated vitamin E deficiency (277460), abetalipoproteinemia, and
hypobetalipoproteinemia (605019) were ruled out. Findings on electron
microscopy of the intestinal mucosa were consistent with chylomicron
retention disease. Aguglia et al. (2000) postulated that both CMRD and
MSS were related to defects in a gene crucial for the assembly or
secretion of chylomicron particles. In the brothers reported by Aguglia
et al. (2000), Jones et al. (2003) identified a mutation in the SAR1B
gene (607690.0006), responsible for CMRD, and Annesi et al. (2007)
identified a mutation in the SIL1 gene (608005.0004), responsible for
MSS. The findings indicated that the patients had 2 distinct diseases
due to mutations in 2 different genes, rather than defects in a single
gene leading to both disorders.
OTHER FEATURES
Silvain et al. (2008) reported increased serum creatine kinase in 8 CMRD
patients between the ages of 13 and 39 years. Two patients had mild
clinical symptoms suggestive of mechanical muscle irritability, but none
had frank muscle weakness. A 38-year-old woman had increased CK-MB, but
no evidence of cardiac dysfunction. A 35-year-old woman had normal serum
CK-MB, but decreased cardiac ejection fraction.
INHERITANCE
Lamy et al. (1967) reported 2 affected brothers, and Silverberg et al.
(1968) noted parental consanguinity, both suggesting autosomal recessive
inheritance.
PATHOGENESIS
By in vitro studies of small intestinal explants from CMRD patients,
Levy et al. (1987) found normal apoB-48 protein synthesis, but deficient
glycosylation. The authors postulated a defect in the formation and
secretion of chylomicrons resulting from a defect in glycosylation.
Dannoura et al. (1999) studied 8 patients with Anderson disease from 7
unrelated families of North African origin after treatment with a
low-fat diet. Lipid loading of intestinal biopsies persisted, but the
pattern and the extent of loading varied among the patients. Electron
microscopy showed lipoprotein-like particles in membrane-bound
compartments, the densities and mean diameters of which were, in
general, significantly larger than in normal-fed subjects. There were
also large lipid particles with diameters up to 7,043 nm that were not
surrounded by a membrane. Rarely, lipoprotein-like particles were
observed in the intercellular spaces. All of these changes could be seen
in all patients. Intestinal organ cultures showed that apolipoprotein B
and apolipoprotein A-IV (APOA4; 107690) were synthesized with apparently
normal molecular masses and that small amounts were secreted in
lipid-bound forms. Normal microsomal triglyceride transfer protein (MTP;
157147) and activity were also detected in intestinal biopsies.
Segregation analyses of 4 families excluded involvement of significant
regions of the genome surrounding the genes encoding the apolipoproteins
expressed in the intestine, as well as the genes encoding 3
intracellular lipid transport proteins, MTP, FABP1 (134650), and FABPZ
(134640). The results suggested that factors other than apolipoproteins
and MTP are important for human intestinal chylomicron assembly and
secretion.
Duden (2003) noted that although endoplasmic reticulum-to-Golgi
trafficking has been well characterized by both genetic and biochemical
methods, few human disorders have been attributed to defects in its
individual components. It is likely that the functional redundancy of
the COPII pathway leads to nonlethal phenotypes that have escaped
classification. Three disorders due to defects in this system are CMRD
disease, X-linked spondyloepiphyseal dysplasia tarda (313400), and
combined deficiency of clotting factors V and VIII (277300).
MOLECULAR GENETICS
- Mutations in the SAR1B Gene
Jones et al. (2003) identified a region of apparent homozygosity on
chromosome 5q31.1 that segregated with affected status in 4 families
with CMRD. In 10 affected individuals from 7 families with chylomicron
retention disease, Jones et al. (2003) identified homozygous or compound
heterozygous mutations in the SAR1B gene (see, e.g.,
607690.0001-607690.0005). Several of the patients had previously been
reported (Bouma et al., 1986), Roy et al. (1987), Nemeth et al. (1995),
and Dannoura et al. (1999).
- Exclusion Studies
Pessah et al. (1991) provided clear genetic evidence that Anderson
disease is not due to a defect in the APOB gene: RFLP studies in 2
families indicated that affected children inherited different APOB
alleles from at least 1 parent. Strich et al. (1993) arrived at the same
conclusion from study of a family in which 3 of 7 children with
consanguineous parents were affected. All 3 suffered from diarrhea,
failure to thrive, and recurrent infections during infancy. Although the
symptoms disappeared later in life, biochemical disorders (e.g., low
plasma levels of apolipoproteins A1 (107680) and B as well as
cholesterol, resulting in avitaminosis E, plus failure to secrete
chylomicrons after a fat meal) persisted. Electron microscopy of
enterocytes in 1 of the patients showed accumulation of lipid vacuoles.
A VNTR polymorphism linked to the APOB locus excluded that gene as the
site of the mutation.
*FIELD* RF
1. Aguglia, U.; Annesi, G.; Pasquinelli, G.; Spadafora, P.; Gambardella,
A.; Annesi, F.; Pasqua, A. A.; Cavalcanti, F.; Crescibene, L.; Bagala,
A.; Bono, F.; Oliveri, R. L.; Valentino, P.; Zappia, M.; Quattrone,
A.: Vitamin E deficiency due to chylomicron retention disease in
Marinesco-Sjogren syndrome. Ann. Neurol. 47: 260-264, 2000.
2. Anderson, C. M.; Townley, R. R. W.; Freeman, M.; Johansen, P.:
Unusual causes of steatorrhoea in infancy and childhood. Med. J.
Aust. 2: 617-622, 1961.
3. Annesi, G.; Aguglia, U.; Tarantino, P.; Annesi, F.; De Marco, E.
V.; Civitelli, D.; Torroni, A.; Quattrone, A.: SIL1 and SARA2 mutations
in Marinesco-Sjogren and chylomicron retention disease. (Letter) Clin.
Genet. 71: 288-289, 2007.
4. Bouma, M.-E.; Beucler, I.; Aggerbeck, L.-P.; Infante, R.; Schmitz,
J.: Hypobetalipoproteinemia with accumulation of an apoprotein B-like
protein in intestinal cells: immunoenzymatic and biochemical characterization
of seven cases of Anderson's disease. J. Clin. Invest. 78: 398-410,
1986.
5. Dannoura, A. H.; Berriot-Varoqueaux, N.; Amati, P.; Abadie, V.;
Verthier, N.; Schmitz, J.; Wetterau, J. R.; Samson-Bouma, M.-E.; Aggerbeck,
L. P.: Anderson's disease: exclusion of apolipoprotein and intracellular
lipid transport genes. Arterioscler. Thromb. Vasc. Biol. 19: 2494-2508,
1999.
6. Duden, R.: ER-to-Golgi transport: COPI and COPII function (review). Molec.
Membr. Biol. 20: 197-207, 2003.
7. Jones, B.; Jones, E. L.; Bonney, S. A.; Patel, H. N.; Mensenkamp,
A. R.; Eichenbaum-Voline, S.; Rudling, M.; Myrdal, U.; Annesi, G.;
Naik, S.; Meadows, N.; Quattrone, A.; and 9 others: Mutations in
a Sar1 GTPase of COPII vesicles are associated with lipid absorption
disorders. Nature Genet. 34: 29-31, 2003.
8. Kane, J. P.; Havel, R. J.: Disorders of the biogenesis and secretion
of lipoproteins containing the B apolipoproteins.In: Scriver, C. R.;
Beaudet, A. L.; Sly, W. S.; Valle, D.: The Metabolic Basis of Inherited
Disease. New York: McGraw-Hill (pub.) (6th ed.) I: 1989. Pp.
1154-1155.
9. Lamy, M.; Frezal, J.; Rey, J.; Jos, J.; Nezelof, C.; Herrault,
A.; Cohen-Solal, J.: Diarrhee chronique par trouble du transfert
intra-cellulaire des lipides. Arch. Franc. Pediat. 24: 1079 only,
1967.
10. Levy, E.; Marcel, Y.; Deckelbaum, R. J.; Milne, R.; Lepage, G.;
Seidman, E.; Bendayan, M.; Roy, C. C.: Intestinal apoB synthesis,
lipids and lipoproteins in chylomicron retention disease. J. Lipid
Res. 28: 1263-1274, 1987. Note: Erratum: J. Lipid. Res.: 29: 119
only, 1988.
11. Nemeth, A.; Myrdal, U.; veress, B.; Rudling, M.; Berglund, L.;
Angelin, B.: Studies on lipoprotein metabolism in a family with jejunal
chylomicron retention. Europ. J. Clin. Invest. 25: 271-280, 1995.
12. Pessah, M.; Benlian, P.; Beucler, I.; Loux, N.; Schmitz, J.; Junien,
C.; Infante, R.: Anderson's disease: genetic exclusion of the apolipoprotein-B
gene in two families. J. Clin. Invest. 87: 367-370, 1991.
13. Roy, C. C.; Levy, E.; Green, P. H. R.; Sniderman, A.; Letarte,
J.; Buts, J. P.; Orquin, J.; Brochu, P.; Weber, A. M.; Morin, C. L.;
Marcel, Y.; Deckelbaum, R. J.: Malabsorption, hypocholesterolemia,
and fat-filled enterocytes with increased intestinal apoprotein B:
chylomicron retention disease. Gastroenterology 92: 390-399, 1987.
14. Silvain, M.; Bligny, D.; Aparicio, T.; Laforet, P.; Grodet, A.;
Peretti, N.; Menard, D.; Djouadi, F.; Jardel, C.; Begue, J. M.; Walker,
F.; Schmitz, J.; Lachaux, A.; Aggerbeck, L. P.; Samson-Bouma, M. E.
: Anderson's disease (chylomicron retention disease): a new mutation
in the SARA2 gene associated with muscular and cardiac abnormalities. Clin.
Genet. 74: 546-552, 2008.
15. Silverberg, M.; Kessler, J.; Neumann, P. Z.; Wiglesworth, F. W.
: An intestinal lipid transport defect. A possible variant of hypo-beta-lipoproteinemia.
(Abstract) Gastroenterology 54: 1271-1272, 1968.
16. Strich, D.; Goldstein, R.; Phillips, A.; Shemer, R.; Goldberg,
Y.; Razin, A.; Freier, S.: Anderson's disease: no linkage to the
apo B locus. J. Pediat. Gastroent. Nutr. 16: 257-264, 1993.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Other];
Failure to thrive;
Growth retardation
ABDOMEN:
[Gastrointestinal];
Fat malabsorption;
Severe diarrhea;
Steatorrhea;
Malnutrition;
Vomiting;
Jejunal endoscopy shows white epithelium;
Small bowel enterocytes accumulate lipid droplets in membrane-bound
compartments or in the cytoplasm
NEUROLOGIC:
[Peripheral nervous system];
Neurologic deficits may occur secondarily to malabsorption;
Peripheral neuropathy;
Diminished or absent deep tendon reflexes;
Diminished vibratory sense
LABORATORY ABNORMALITIES:
Hypocholesterolemia;
Deficiency of fat-soluble vitamins;
Normal serum triglycerides;
Absence of chylomicrons in lymph and plasma;
Defect in chylomicron secretion;
Hypobetalipoproteinemia
MISCELLANEOUS:
Onset in infancy
MOLECULAR BASIS:
Caused by mutation in the SAR1, S. cerevisiae, homolog B gene (SAR1B,
607690.0001)
*FIELD* CN
Cassandra L. Kniffin - revised: 2/23/2009
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
joanna: 05/14/2009
ckniffin: 2/23/2009
alopez: 4/15/2003
*FIELD* CN
Cassandra L. Kniffin - updated: 2/23/2009
Cassandra L. Kniffin - updated: 8/29/2007
Victor A. McKusick - updated: 10/26/2006
Victor A. McKusick - updated: 4/14/2003
Victor A. McKusick - updated: 3/9/2001
Victor A. McKusick - updated: 1/19/2000
*FIELD* CD
Victor A. McKusick: 6/3/1986
*FIELD* ED
carol: 12/04/2013
wwang: 5/23/2011
wwang: 4/2/2009
ckniffin: 2/23/2009
carol: 1/26/2009
wwang: 9/11/2007
ckniffin: 8/29/2007
alopez: 11/1/2006
terry: 10/26/2006
alopez: 3/17/2004
alopez: 4/30/2003
alopez: 4/15/2003
terry: 4/14/2003
cwells: 3/30/2001
terry: 3/9/2001
mcapotos: 1/27/2000
mcapotos: 1/20/2000
terry: 1/19/2000
davew: 8/19/1994
mimadm: 4/14/1994
warfield: 3/30/1994
carol: 6/3/1993
supermim: 3/17/1992
carol: 1/24/1991
MIM
607690
*RECORD*
*FIELD* NO
607690
*FIELD* TI
*607690 SAR1, S. CEREVISIAE, HOMOLOG B; SAR1B
;;SAR1A, S. CEREVISIAE, HOMOLOG 2; SARA2
read more*FIELD* TX
CLONING
By searching databases, followed by PCR, He et al. (2002) cloned human
SAR1B, which they called SARA1. The deduced 198-amino acid SARA1 protein
contains 4 highly conserved GTPase motifs. Northern blot analysis
detected strong expression of a major transcript of 2.4 to 4.4 kb in all
tissues examined. Smaller and larger variants were also detected in most
tissues.
By a genomewide screen of 6 affected families to find a gene mutant in
lipid absorption disorders, Jones et al. (2003) identified the SAR1B
gene, which they called SARA2, in a region of apparent homozygosity on
5q31.1 shared by 4 affected families. SAR1B belongs to the
Sar1-ADP-ribosylation factor family of small GTPases (Takai et al.,
2001), which govern the intracellular trafficking of proteins in coat
protein (COP)-coated vesicles (Schekman and Orci, 1996). The human
SARA1B protein shares 99% amino acid identity with hamster Sar1. SARA1B
is expressed in many tissues including small intestine, liver, muscle,
and brain.
GENE STRUCTURE
He et al. (2002) determined that the SAR1B gene contains 8 exons and
spans over 60 kb.
Jones et al. (2003) determined that the human SAR1B gene comprises 7
exons.
MAPPING
By radiation hybrid analysis, He et al. (2002) mapped the SAR1B gene to
chromosome 5q23-q31.1.
The SAR1B gene maps to chromosome 5q31.1, within 94 kb of the SEC24A
gene (607183) (Jones et al., 2003).
MOLECULAR GENETICS
Chylomicron retention disease (CMRD; 246700), also known as Anderson
disease is an autosomal recessive disorder of severe fat malabsorption
associated with failure to thrive in infancy. The condition is
characterized by deficiency of fat-soluble vitamins, low blood
cholesterol levels, and a selective absence of chylomicrons from blood.
Affected individuals accumulate chylomicron-like particles in
membrane-bound compartments of enterocytes, which contain large
cytosolic lipid droplets. In affected members of several families with
CMRD, Jones et al. (2003) identified homozygous or compound heterozygous
mutations in the SAR1B gene (607690.0001-607690.0006). Jones et al.
(2003) found no mutations in a second human isoform SAR1A (607691),
located on chromosome 10, in families with these disorders.
Charcosset et al. (2008) identified mutations in the SAR1B gene (see,
e.g., 607690.0007; 607690.0008) in families with CMRD.
*FIELD* AV
.0001
CHYLOMICRON RETENTION DISEASE
SAR1B, GLY37ARG
In 2 members of an Algerian family with chylomicron retention disease
(246700), Jones et al. (2003) identified homozygosity for a 109G-A
transition in the SAR1B gene that caused a gly37-to-arg (G37R) amino
acid change, with the result that the protein had no affinity for
GDP/GTP. Both parents were heterozygous.
.0002
CHYLOMICRON RETENTION DISEASE
SAR1B, ASP137ASN
In 2 white Canadian families, Jones et al. (2003) found that affected
individuals with CMRD (246700) were homozygous for a 409G-A transition
in the SAR1B gene that resulted in an asp137 amino acid change (D137N)
and reduced affinity of the protein for GDP/GTP. In a third white
Canadian family, a single affected individual was a compound
heterozygote for the D137N mutation and a deletion of 2 nucleotides,
75-76delTG. The change occurring in leu28 resulted in frameshift and
premature termination at codon 34 (L28fsX34).
Charcosset et al. (2008) identified the D137N mutation in 3 additional
French Canadian families with chylomicron retention disease.
.0003
CHYLOMICRON RETENTION DISEASE
SAR1B, 2-BP DEL, 75TG
See Jones et al. (2003) and 607690.0002.
.0004
CHYLOMICRON RETENTION DISEASE
SAR1B, SER179ARG
In a white Canadian family, Jones et al. (2003) found that CMRD (246700)
was associated with homozygosity for a ser179-to-arg (S179R) mutation
arising from a 537T-A transversion in the SAR1B gene that resulted in
loss of affinity of the protein for GDP/GTP.
Charcosset et al. (2008) identified the S179R mutation in 3 additional
French Canadian families with chylomicron retention disease.
.0005
CHYLOMICRON RETENTION DISEASE
SAR1B, 4-BP DUP, 555TTAC
In a Turkish family, Jones et al. (2003) demonstrated that 2 children
with CMRD (246700) were homozygous for a 4-bp duplication of 555-558TTAC
in the SAR1B gene. The mutated allele replaced amino acids 187-198 of
the SARA2 protein with a new amino acid sequence. The translation was
arrested after codon 198. The mutation was predicted to affect helix 6
and to cause reduced affinity for the endoplasmic reticulum (ER)
membrane.
.0006
CHYLOMICRON RETENTION DISEASE
SAR1B, 349, G-C, -1
In an Italian family in which 2 brothers had chylomicron retention
disease (246700) and Marinesco-Sjogren syndrome (MSS; 248800), reported
by Aguglia et al. (2000), Jones et al. (2003) found homozygosity for a
splice site mutation in the SAR1B gene (349-1G-C). It was predicted that
this mutation could cause exon skipping, activation of a nearby cryptic
splice site, or production of an unspliced mRNA, any of which would
substantially disrupt the protein. In the same patients, Annesi et al.
(2007) identified a mutation in the SIL1 gene (R111X; 608005.0004),
responsible for MSS. The findings indicated that the patients had 2
distinct diseases due to mutations in 2 different genes, rather than
defects in a single gene leading to both disorders.
.0007
CHYLOMICRON RETENTION DISEASE
SAR1B, GLU122TER
In affected members of a Turkish family with chylomicron retention
disease (246700), Charcosset et al. (2008) identified a homozygous
364G-C transversion in the SAR1B gene, resulting in a glu122-to-ter
(E122X) substitution.
.0008
CHYLOMICRON RETENTION DISEASE
SAR1B, GLY185VAL
In a Portuguese child with chylomicron retention disease (246700),
Charcosset et al. (2008) identified a homozygous 554G-T transversion in
the SAR1B gene, resulting in a gly185-to-val (G185V) substitution.
*FIELD* RF
1. Aguglia, U.; Annesi, G.; Pasquinelli, G.; Spadafora, P.; Gambardella,
A.; Annesi, F.; Pasqua, A. A.; Cavalcanti, F.; Crescibene, L.; Bagala,
A.; Bono, F.; Oliveri, R. L.; Valentino, P.; Zappia, M.; Quattrone,
A.: Vitamin E deficiency due to chylomicron retention disease in
Marinesco-Sjogren syndrome. Ann. Neurol. 47: 260-264, 2000.
2. Annesi, G.; Aguglia, U.; Tarantino, P.; Annesi, F.; De Marco, E.
V.; Civitelli, D.; Torroni, A.; Quattrone, A.: SIL1 and SARA2 mutations
in Marinesco-Sjogren and chylomicron retention disease. (Letter) Clin.
Genet. 71: 288-289, 2007.
3. Charcosset, M.; Sassolas, A.; Peretti, N.; Roy, C. C.; Deslandres,
C.; Sinnett, D.; Levy, E.; Lachaux, A.: Anderson or chylomicron retention
disease: molecular impact of five mutations in the SAR1B gene on the
structure and the functionality of Sar1b protein. Molec. Genet. Metab. 93:
74-84, 2008.
4. He, H.; Dai, F.; Yu, L.; She, X.; Zhao, Y.; Jiang, J.; Chen, X.;
Zhao, S.: Identification and characterization of nine novel human
small GTPases showing variable expressions in liver cancer tissues. Gene
Expr. 10: 231-242, 2002.
5. Jones, B.; Jones, E. L.; Bonney, S. A.; Patel, H. N.; Mensenkamp,
A. R.; Eichenbaum-Voline, S.; Rudling, M.; Myrdal, U.; Annesi, G.;
Naik, S.; Meadows, N.; Quattrone, A.; and 9 others: Mutations in
a Sar1 GTPase of COPII vesicles are associated with lipid absorption
disorders. Nature Genet. 34: 29-31, 2003.
6. Schekman, R.; Orci, L.: Coat proteins and vesicle budding. Science 271:
1526-1533, 1996.
7. Takai, Y.; Sasaki, T.; Matozaki, T.: Small GTP-binding proteins. Physiol.
Rev. 81: 154-208, 2001.
*FIELD* CN
Patricia A. Hartz - updated: 7/23/2009
Cassandra L. Kniffin - updated: 2/23/2009
Cassandra L. Kniffin - updated: 8/29/2007
*FIELD* CD
Victor A. McKusick: 4/15/2003
*FIELD* ED
mgross: 08/18/2009
terry: 7/23/2009
wwang: 4/2/2009
ckniffin: 2/23/2009
wwang: 9/11/2007
ckniffin: 8/29/2007
terry: 7/24/2003
alopez: 4/30/2003
alopez: 4/15/2003
*RECORD*
*FIELD* NO
607690
*FIELD* TI
*607690 SAR1, S. CEREVISIAE, HOMOLOG B; SAR1B
;;SAR1A, S. CEREVISIAE, HOMOLOG 2; SARA2
read more*FIELD* TX
CLONING
By searching databases, followed by PCR, He et al. (2002) cloned human
SAR1B, which they called SARA1. The deduced 198-amino acid SARA1 protein
contains 4 highly conserved GTPase motifs. Northern blot analysis
detected strong expression of a major transcript of 2.4 to 4.4 kb in all
tissues examined. Smaller and larger variants were also detected in most
tissues.
By a genomewide screen of 6 affected families to find a gene mutant in
lipid absorption disorders, Jones et al. (2003) identified the SAR1B
gene, which they called SARA2, in a region of apparent homozygosity on
5q31.1 shared by 4 affected families. SAR1B belongs to the
Sar1-ADP-ribosylation factor family of small GTPases (Takai et al.,
2001), which govern the intracellular trafficking of proteins in coat
protein (COP)-coated vesicles (Schekman and Orci, 1996). The human
SARA1B protein shares 99% amino acid identity with hamster Sar1. SARA1B
is expressed in many tissues including small intestine, liver, muscle,
and brain.
GENE STRUCTURE
He et al. (2002) determined that the SAR1B gene contains 8 exons and
spans over 60 kb.
Jones et al. (2003) determined that the human SAR1B gene comprises 7
exons.
MAPPING
By radiation hybrid analysis, He et al. (2002) mapped the SAR1B gene to
chromosome 5q23-q31.1.
The SAR1B gene maps to chromosome 5q31.1, within 94 kb of the SEC24A
gene (607183) (Jones et al., 2003).
MOLECULAR GENETICS
Chylomicron retention disease (CMRD; 246700), also known as Anderson
disease is an autosomal recessive disorder of severe fat malabsorption
associated with failure to thrive in infancy. The condition is
characterized by deficiency of fat-soluble vitamins, low blood
cholesterol levels, and a selective absence of chylomicrons from blood.
Affected individuals accumulate chylomicron-like particles in
membrane-bound compartments of enterocytes, which contain large
cytosolic lipid droplets. In affected members of several families with
CMRD, Jones et al. (2003) identified homozygous or compound heterozygous
mutations in the SAR1B gene (607690.0001-607690.0006). Jones et al.
(2003) found no mutations in a second human isoform SAR1A (607691),
located on chromosome 10, in families with these disorders.
Charcosset et al. (2008) identified mutations in the SAR1B gene (see,
e.g., 607690.0007; 607690.0008) in families with CMRD.
*FIELD* AV
.0001
CHYLOMICRON RETENTION DISEASE
SAR1B, GLY37ARG
In 2 members of an Algerian family with chylomicron retention disease
(246700), Jones et al. (2003) identified homozygosity for a 109G-A
transition in the SAR1B gene that caused a gly37-to-arg (G37R) amino
acid change, with the result that the protein had no affinity for
GDP/GTP. Both parents were heterozygous.
.0002
CHYLOMICRON RETENTION DISEASE
SAR1B, ASP137ASN
In 2 white Canadian families, Jones et al. (2003) found that affected
individuals with CMRD (246700) were homozygous for a 409G-A transition
in the SAR1B gene that resulted in an asp137 amino acid change (D137N)
and reduced affinity of the protein for GDP/GTP. In a third white
Canadian family, a single affected individual was a compound
heterozygote for the D137N mutation and a deletion of 2 nucleotides,
75-76delTG. The change occurring in leu28 resulted in frameshift and
premature termination at codon 34 (L28fsX34).
Charcosset et al. (2008) identified the D137N mutation in 3 additional
French Canadian families with chylomicron retention disease.
.0003
CHYLOMICRON RETENTION DISEASE
SAR1B, 2-BP DEL, 75TG
See Jones et al. (2003) and 607690.0002.
.0004
CHYLOMICRON RETENTION DISEASE
SAR1B, SER179ARG
In a white Canadian family, Jones et al. (2003) found that CMRD (246700)
was associated with homozygosity for a ser179-to-arg (S179R) mutation
arising from a 537T-A transversion in the SAR1B gene that resulted in
loss of affinity of the protein for GDP/GTP.
Charcosset et al. (2008) identified the S179R mutation in 3 additional
French Canadian families with chylomicron retention disease.
.0005
CHYLOMICRON RETENTION DISEASE
SAR1B, 4-BP DUP, 555TTAC
In a Turkish family, Jones et al. (2003) demonstrated that 2 children
with CMRD (246700) were homozygous for a 4-bp duplication of 555-558TTAC
in the SAR1B gene. The mutated allele replaced amino acids 187-198 of
the SARA2 protein with a new amino acid sequence. The translation was
arrested after codon 198. The mutation was predicted to affect helix 6
and to cause reduced affinity for the endoplasmic reticulum (ER)
membrane.
.0006
CHYLOMICRON RETENTION DISEASE
SAR1B, 349, G-C, -1
In an Italian family in which 2 brothers had chylomicron retention
disease (246700) and Marinesco-Sjogren syndrome (MSS; 248800), reported
by Aguglia et al. (2000), Jones et al. (2003) found homozygosity for a
splice site mutation in the SAR1B gene (349-1G-C). It was predicted that
this mutation could cause exon skipping, activation of a nearby cryptic
splice site, or production of an unspliced mRNA, any of which would
substantially disrupt the protein. In the same patients, Annesi et al.
(2007) identified a mutation in the SIL1 gene (R111X; 608005.0004),
responsible for MSS. The findings indicated that the patients had 2
distinct diseases due to mutations in 2 different genes, rather than
defects in a single gene leading to both disorders.
.0007
CHYLOMICRON RETENTION DISEASE
SAR1B, GLU122TER
In affected members of a Turkish family with chylomicron retention
disease (246700), Charcosset et al. (2008) identified a homozygous
364G-C transversion in the SAR1B gene, resulting in a glu122-to-ter
(E122X) substitution.
.0008
CHYLOMICRON RETENTION DISEASE
SAR1B, GLY185VAL
In a Portuguese child with chylomicron retention disease (246700),
Charcosset et al. (2008) identified a homozygous 554G-T transversion in
the SAR1B gene, resulting in a gly185-to-val (G185V) substitution.
*FIELD* RF
1. Aguglia, U.; Annesi, G.; Pasquinelli, G.; Spadafora, P.; Gambardella,
A.; Annesi, F.; Pasqua, A. A.; Cavalcanti, F.; Crescibene, L.; Bagala,
A.; Bono, F.; Oliveri, R. L.; Valentino, P.; Zappia, M.; Quattrone,
A.: Vitamin E deficiency due to chylomicron retention disease in
Marinesco-Sjogren syndrome. Ann. Neurol. 47: 260-264, 2000.
2. Annesi, G.; Aguglia, U.; Tarantino, P.; Annesi, F.; De Marco, E.
V.; Civitelli, D.; Torroni, A.; Quattrone, A.: SIL1 and SARA2 mutations
in Marinesco-Sjogren and chylomicron retention disease. (Letter) Clin.
Genet. 71: 288-289, 2007.
3. Charcosset, M.; Sassolas, A.; Peretti, N.; Roy, C. C.; Deslandres,
C.; Sinnett, D.; Levy, E.; Lachaux, A.: Anderson or chylomicron retention
disease: molecular impact of five mutations in the SAR1B gene on the
structure and the functionality of Sar1b protein. Molec. Genet. Metab. 93:
74-84, 2008.
4. He, H.; Dai, F.; Yu, L.; She, X.; Zhao, Y.; Jiang, J.; Chen, X.;
Zhao, S.: Identification and characterization of nine novel human
small GTPases showing variable expressions in liver cancer tissues. Gene
Expr. 10: 231-242, 2002.
5. Jones, B.; Jones, E. L.; Bonney, S. A.; Patel, H. N.; Mensenkamp,
A. R.; Eichenbaum-Voline, S.; Rudling, M.; Myrdal, U.; Annesi, G.;
Naik, S.; Meadows, N.; Quattrone, A.; and 9 others: Mutations in
a Sar1 GTPase of COPII vesicles are associated with lipid absorption
disorders. Nature Genet. 34: 29-31, 2003.
6. Schekman, R.; Orci, L.: Coat proteins and vesicle budding. Science 271:
1526-1533, 1996.
7. Takai, Y.; Sasaki, T.; Matozaki, T.: Small GTP-binding proteins. Physiol.
Rev. 81: 154-208, 2001.
*FIELD* CN
Patricia A. Hartz - updated: 7/23/2009
Cassandra L. Kniffin - updated: 2/23/2009
Cassandra L. Kniffin - updated: 8/29/2007
*FIELD* CD
Victor A. McKusick: 4/15/2003
*FIELD* ED
mgross: 08/18/2009
terry: 7/23/2009
wwang: 4/2/2009
ckniffin: 2/23/2009
wwang: 9/11/2007
ckniffin: 8/29/2007
terry: 7/24/2003
alopez: 4/30/2003
alopez: 4/15/2003