G6PC3_HUMAN
ID G6PC3_HUMAN Reviewed; 346 AA.
AC Q9BUM1; Q8WU15;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Glucose-6-phosphatase 3;
DE Short=G-6-Pase 3;
DE Short=G6Pase 3;
DE EC=3.1.3.9;
DE AltName: Full=Glucose-6-phosphatase beta;
DE Short=G6Pase-beta;
DE AltName: Full=Ubiquitous glucose-6-phosphatase catalytic subunit-related protein;
GN Name=G6PC3; Synonyms=UGRP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye, and Skin;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12370122; DOI=10.1677/jme.0.0290205;
RA Martin C.C., Oeser J.K., Svitek C.A., Hunter S.I., Hutton J.C.,
RA O'Brien R.M.;
RT "Identification and characterization of a human cDNA and gene encoding a
RT ubiquitously expressed glucose-6-phosphatase catalytic subunit-related
RT protein.";
RL J. Mol. Endocrinol. 29:205-222(2002).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE
RP SPECIFICITY.
RX PubMed=12965222; DOI=10.1016/s0014-5793(03)00903-7;
RA Guionie O., Clottes E., Stafford K., Burchell A.;
RT "Identification and characterisation of a new human glucose-6-phosphatase
RT isoform.";
RL FEBS Lett. 551:159-164(2003).
RN [5]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF ARG-79; HIS-114 AND HIS-167.
RX PubMed=13129915; DOI=10.1074/jbc.m309472200;
RA Shieh J.-J., Pan C.-J., Mansfield B.C., Chou J.Y.;
RT "A glucose-6-phosphate hydrolase, widely expressed outside the liver, can
RT explain age-dependent resolution of hypoglycemia in glycogen storage
RT disease type Ia.";
RL J. Biol. Chem. 278:47098-47103(2003).
RN [6]
RP TOPOLOGY, AND ACTIVE SITE.
RX PubMed=14718531; DOI=10.1074/jbc.m313271200;
RA Ghosh A., Shieh J.-J., Pan C.-J., Chou J.Y.;
RT "Histidine 167 is the phosphate acceptor in glucose-6-phosphatase-beta
RT forming a phosphohistidine enzyme intermediate during catalysis.";
RL J. Biol. Chem. 279:12479-12483(2004).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=14765991; DOI=10.1677/jme.0.0320033;
RA Boustead J.N., Martin C.C., Oeser J.K., Svitek C.A., Hunter S.I.,
RA Hutton J.C., O'Brien R.M.;
RT "Identification and characterization of a cDNA and the gene encoding the
RT mouse ubiquitously expressed glucose-6-phosphatase catalytic subunit-
RT related protein.";
RL J. Mol. Endocrinol. 32:33-53(2004).
RN [8]
RP VARIANTS SCN4 PRO-185; HIS-253 AND ARG-262, AND CHARACTERIZATION OF VARIANT
RP SCN4 HIS-253.
RX PubMed=19118303; DOI=10.1056/nejmoa0805051;
RA Boztug K., Appaswamy G., Ashikov A., Schaeffer A.A., Salzer U.,
RA Diestelhorst J., Germeshausen M., Brandes G., Lee-Gossler J., Noyan F.,
RA Gatzke A.-K., Minkov M., Greil J., Kratz C., Petropoulou T., Pellier I.,
RA Bellanne-Chantelot C., Rezaei N., Moenkemoeller K., Irani-Hakimeh N.,
RA Bakker H., Gerardy-Schahn R., Zeidler C., Grimbacher B., Welte K.,
RA Klein C.;
RT "A syndrome with congenital neutropenia and mutations in G6PC3.";
RL N. Engl. J. Med. 360:32-43(2009).
RN [9]
RP VARIANT DURSS VAL-116.
RX PubMed=20799326; DOI=10.1002/ajmg.a.33615;
RA Banka S., Newman W.G., Ozgul R.K., Dursun A.;
RT "Mutations in the G6PC3 gene cause Dursun syndrome.";
RL Am. J. Med. Genet. A 152:2609-2611(2010).
RN [10]
RP VARIANT SCN4 ARG-260, AND CHARACTERIZATION OF VARIANT SCN4 ARG-260.
RX PubMed=20616219; DOI=10.1182/blood-2010-01-265942;
RA McDermott D.H., De Ravin S.S., Jun H.S., Liu Q., Priel D.A., Noel P.,
RA Takemoto C.M., Ojode T., Paul S.M., Dunsmore K.P., Hilligoss D.,
RA Marquesen M., Ulrick J., Kuhns D.B., Chou J.Y., Malech H.L., Murphy P.M.;
RT "Severe congenital neutropenia resulting from G6PC3 deficiency with
RT increased neutrophil CXCR4 expression and myelokathexis.";
RL Blood 116:2793-2802(2010).
RN [11]
RP VARIANTS SCN4 LYS-116; GLN-189 AND ARG-260.
RX PubMed=20220065; DOI=10.3324/haematol.2009.017665;
RA Germeshausen M., Zeidler C., Stuhrmann M., Lanciotti M., Ballmaier M.,
RA Welte K.;
RT "Digenic mutations in severe congenital neutropenia.";
RL Haematologica 95:1207-1210(2010).
RN [12]
RP VARIANTS SCN4 SER-44; 64-THR--ILE-70 DEL AND ARG-208, AND CHARACTERIZATION
RP OF VARIANTS SCN4 SER-44 AND 64-THR--ILE-70 DEL.
RX PubMed=22469094; DOI=10.1111/j.1365-2141.2012.09110.x;
RA Smith B.N., Evans C., Ali A., Ancliff P.J., Hayee B., Segal A.W., Hall G.,
RA Kaya Z., Shakoori A.R., Linch D.C., Gale R.E.;
RT "Phenotypic heterogeneity and evidence of a founder effect associated with
RT G6PC3 mutations in patients with severe congenital neutropenia.";
RL Br. J. Haematol. 158:146-149(2012).
RN [13]
RP VARIANTS SCN4 LEU-44; LYS-116; ILE-139; GLN-161; HIS-253; ARG-260 AND
RP ASP-260.
RX PubMed=22050868; DOI=10.1016/j.jpeds.2011.09.019;
RA Boztug K., Rosenberg P.S., Dorda M., Banka S., Moulton T., Curtin J.,
RA Rezaei N., Corns J., Innis J.W., Avci Z., Tran H.C., Pellier I.,
RA Pierani P., Fruge R., Parvaneh N., Mamishi S., Mody R., Darbyshire P.,
RA Motwani J., Murray J., Buchanan G.R., Newman W.G., Alter B.P., Boxer L.A.,
RA Donadieu J., Welte K., Klein C.;
RT "Extended spectrum of human glucose-6-phosphatase catalytic subunit 3
RT deficiency: novel genotypes and phenotypic variability in severe congenital
RT neutropenia.";
RL J. Pediatr. 160:679-683(2012).
RN [14]
RP VARIANT SCN4 ARG-325.
RX PubMed=24105461; DOI=10.1007/s10875-013-9945-7;
RA Alangari A.A., Alsultan A., Osman M.E., Anazi S., Alkuraya F.S.;
RT "A novel homozygous mutation in G6PC3 presenting as cyclic neutropenia and
RT severe congenital neutropenia in the same family.";
RL J. Clin. Immunol. 33:1403-1406(2013).
RN [15]
RP VARIANTS SCN4 SER-44; THR-116 AND CYS-253.
RX PubMed=23298686; DOI=10.1016/j.ymgme.2012.12.001;
RA Banka S., Wynn R., Byers H., Arkwright P.D., Newman W.G.;
RT "G6PC3 mutations cause non-syndromic severe congenital neutropenia.";
RL Mol. Genet. Metab. 108:138-141(2013).
RN [16]
RP VARIANT SCN4 PRO-154.
RX PubMed=23018568; DOI=10.1097/mph.0b013e3182679000;
RA Aytekin C., Germeshausen M., Tuygun N., Dogu F., Ikinciogullari A.;
RT "A novel G6PC3 gene mutation in a patient with severe congenital
RT neutropenia.";
RL J. Pediatr. Hematol. Oncol. 35:E81-E83(2013).
RN [17]
RP VARIANT SCN4 ARG-59.
RX PubMed=24750412; DOI=10.1111/ejh.12349;
RA Arikoglu T., Kuyucu N., Germeshausen M., Kuyucu S.;
RT "A novel G6PC3 gene mutation in severe congenital neutropenia: pancytopenia
RT and variable bone marrow phenotype can also be part of this syndrome.";
RL Eur. J. Haematol. 94:79-82(2015).
RN [18]
RP CHARACTERIZATION OF VARIANTS SCN4 LEU-44; SER-44; ILE-116; LYS-116;
RP THR-116; VAL-116; ARG-118; ILE-139; PRO-154; GLN-161; PRO-185; GLN-189;
RP ARG-208; HIS-253; ARG-260 AND ASP-260.
RX PubMed=25492228; DOI=10.1016/j.ymgme.2014.11.012;
RA Lin S.R., Pan C.J., Mansfield B.C., Chou J.Y.;
RT "Functional analysis of mutations in a severe congenital neutropenia
RT syndrome caused by glucose-6-phosphatase-beta deficiency.";
RL Mol. Genet. Metab. 114:41-45(2015).
CC -!- FUNCTION: Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic
CC reticulum. May form with the glucose-6-phosphate transporter
CC (SLC37A4/G6PT) a ubiquitously expressed complex responsible for glucose
CC production through glycogenolysis and gluconeogenesis. Probably
CC required for normal neutrophil function. {ECO:0000269|PubMed:12370122,
CC ECO:0000269|PubMed:12965222, ECO:0000269|PubMed:13129915}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-glucose 6-phosphate + H2O = D-glucose + phosphate;
CC Xref=Rhea:RHEA:16689, ChEBI:CHEBI:4167, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:61548; EC=3.1.3.9;
CC Evidence={ECO:0000269|PubMed:12965222};
CC -!- ACTIVITY REGULATION: Inhibited by vanadate.
CC {ECO:0000269|PubMed:13129915}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.0 mM for glucose-6-phosphate (at pH 5.5)
CC {ECO:0000269|PubMed:12965222, ECO:0000269|PubMed:13129915};
CC KM=2.0 mM for glucose-6-phosphate (at pH 6.5)
CC {ECO:0000269|PubMed:12965222, ECO:0000269|PubMed:13129915};
CC Note=8 times less active compared to G6PC1 under the same
CC experimental conditions.;
CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:13129915}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:13129915}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Highly expressed in
CC skeletal muscle, at intermediate levels in heart, brain, placenta,
CC kidney, colon, thymus, spleen and pancreas. Also detected in testis,
CC prostate, ovary, liver, lung, small intestine and peripheral blood
CC lymphocytes. {ECO:0000269|PubMed:12370122, ECO:0000269|PubMed:12965222,
CC ECO:0000269|PubMed:14765991}.
CC -!- DISEASE: Neutropenia, severe congenital 4, autosomal recessive (SCN4)
CC [MIM:612541]: A disorder of hematopoiesis characterized by maturation
CC arrest of granulopoiesis at the level of promyelocytes with peripheral
CC blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of
CC severe bacterial infections. {ECO:0000269|PubMed:19118303,
CC ECO:0000269|PubMed:20220065, ECO:0000269|PubMed:20616219,
CC ECO:0000269|PubMed:22050868, ECO:0000269|PubMed:22469094,
CC ECO:0000269|PubMed:23018568, ECO:0000269|PubMed:23298686,
CC ECO:0000269|PubMed:24105461, ECO:0000269|PubMed:24750412,
CC ECO:0000269|PubMed:25492228}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Dursun syndrome (DURSS) [MIM:612541]: A disease characterized
CC by pulmonary arterial hypertension, cardiac abnormalities including
CC secundum-type atrial septal defect, intermittent neutropenia,
CC lymphopenia, monocytosis and anemia. {ECO:0000269|PubMed:20799326}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the glucose-6-phosphatase family. {ECO:0000305}.
CC -!- CAUTION: According to PubMed:12370122, it has no hydrolytic activity.
CC {ECO:0000305}.
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DR EMBL; CH471178; EAW51638.1; -; Genomic_DNA.
DR EMBL; BC002494; AAH02494.2; -; mRNA.
DR EMBL; BC021574; AAH21574.1; -; mRNA.
DR CCDS; CCDS11476.1; -.
DR RefSeq; NP_612396.1; NM_138387.3.
DR AlphaFoldDB; Q9BUM1; -.
DR SMR; Q9BUM1; -.
DR BioGRID; 124957; 12.
DR IntAct; Q9BUM1; 5.
DR MINT; Q9BUM1; -.
DR STRING; 9606.ENSP00000269097; -.
DR DEPOD; G6PC3; -.
DR iPTMnet; Q9BUM1; -.
DR PhosphoSitePlus; Q9BUM1; -.
DR SwissPalm; Q9BUM1; -.
DR BioMuta; G6PC3; -.
DR DMDM; 74733234; -.
DR EPD; Q9BUM1; -.
DR jPOST; Q9BUM1; -.
DR MassIVE; Q9BUM1; -.
DR MaxQB; Q9BUM1; -.
DR PaxDb; Q9BUM1; -.
DR PeptideAtlas; Q9BUM1; -.
DR PRIDE; Q9BUM1; -.
DR ProteomicsDB; 79110; -.
DR Antibodypedia; 59289; 80 antibodies from 17 providers.
DR DNASU; 92579; -.
DR Ensembl; ENST00000269097.9; ENSP00000269097.3; ENSG00000141349.9.
DR GeneID; 92579; -.
DR KEGG; hsa:92579; -.
DR MANE-Select; ENST00000269097.9; ENSP00000269097.3; NM_138387.4; NP_612396.1.
DR UCSC; uc002iex.4; human.
DR CTD; 92579; -.
DR DisGeNET; 92579; -.
DR GeneCards; G6PC3; -.
DR GeneReviews; G6PC3; -.
DR HGNC; HGNC:24861; G6PC3.
DR HPA; ENSG00000141349; Low tissue specificity.
DR MalaCards; G6PC3; -.
DR MIM; 611045; gene.
DR MIM; 612541; phenotype.
DR neXtProt; NX_Q9BUM1; -.
DR OpenTargets; ENSG00000141349; -.
DR Orphanet; 331176; Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency.
DR PharmGKB; PA134968446; -.
DR VEuPathDB; HostDB:ENSG00000141349; -.
DR eggNOG; ENOG502QS5D; Eukaryota.
DR GeneTree; ENSGT00950000183150; -.
DR InParanoid; Q9BUM1; -.
DR OMA; KKWCSRA; -.
DR OrthoDB; 743717at2759; -.
DR PhylomeDB; Q9BUM1; -.
DR TreeFam; TF324388; -.
DR BioCyc; MetaCyc:HS13873-MON; -.
DR BRENDA; 3.1.3.9; 2681.
DR PathwayCommons; Q9BUM1; -.
DR Reactome; R-HSA-3282872; Severe congenital neutropenia type 4 (G6PC3).
DR Reactome; R-HSA-70263; Gluconeogenesis.
DR SABIO-RK; Q9BUM1; -.
DR SignaLink; Q9BUM1; -.
DR SIGNOR; Q9BUM1; -.
DR UniPathway; UPA00138; -.
DR BioGRID-ORCS; 92579; 11 hits in 1080 CRISPR screens.
DR ChiTaRS; G6PC3; human.
DR GeneWiki; G6PC3; -.
DR GenomeRNAi; 92579; -.
DR Pharos; Q9BUM1; Tbio.
DR PRO; PR:Q9BUM1; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9BUM1; protein.
DR Bgee; ENSG00000141349; Expressed in adenohypophysis and 192 other tissues.
DR ExpressionAtlas; Q9BUM1; baseline and differential.
DR Genevisible; Q9BUM1; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0004346; F:glucose-6-phosphatase activity; IMP:UniProtKB.
DR GO; GO:0006094; P:gluconeogenesis; IBA:GO_Central.
DR GO; GO:0051156; P:glucose 6-phosphate metabolic process; IBA:GO_Central.
DR GO; GO:0015760; P:glucose-6-phosphate transport; IEA:Ensembl.
DR InterPro; IPR016275; Glucose-6-phosphatase.
DR InterPro; IPR036938; P_Acid_Pase_2/haloperoxi_sf.
DR InterPro; IPR000326; P_Acid_Pase_2/haloperoxidase.
DR Pfam; PF01569; PAP2; 1.
DR PIRSF; PIRSF000905; Glucose-6-phosphatase; 1.
DR SMART; SM00014; acidPPc; 1.
DR SUPFAM; SSF48317; SSF48317; 1.
PE 1: Evidence at protein level;
KW Disease variant; Endoplasmic reticulum; Gluconeogenesis; Hydrolase;
KW Membrane; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..346
FT /note="Glucose-6-phosphatase 3"
FT /id="PRO_0000334512"
FT TOPO_DOM 1..24
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 25..45
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 46..54
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 55..75
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 76..114
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 115..135
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 136..146
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 147..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 165..169
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..186
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 187..197
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 198..218
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 219..254
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 255..273
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 274..283
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 284..304
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 305..307
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 308..328
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 329..346
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 114
FT /note="Proton donor"
FT /evidence="ECO:0000255"
FT ACT_SITE 167
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:14718531"
FT BINDING 79
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 161
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT VARIANT 44
FT /note="P -> L (in SCN4; complete loss of activity;
FT dbSNP:rs762019955)"
FT /evidence="ECO:0000269|PubMed:22050868,
FT ECO:0000269|PubMed:25492228"
FT /id="VAR_073174"
FT VARIANT 44
FT /note="P -> S (in SCN4; complete loss of activity; purified
FT neutrophils from patients have higher levels of spontaneous
FT and staurosporine-induced apoptosis than controls;
FT dbSNP:rs775224457)"
FT /evidence="ECO:0000269|PubMed:22469094,
FT ECO:0000269|PubMed:23298686, ECO:0000269|PubMed:25492228"
FT /id="VAR_072753"
FT VARIANT 59
FT /note="W -> R (in SCN4; dbSNP:rs752966267)"
FT /evidence="ECO:0000269|PubMed:24750412"
FT /id="VAR_072754"
FT VARIANT 64..70
FT /note="Missing (in SCN4; purified neutrophils from patients
FT have higher levels of spontaneous and staurosporine-induced
FT apoptosis than controls)"
FT /evidence="ECO:0000269|PubMed:22469094"
FT /id="VAR_072755"
FT VARIANT 116
FT /note="M -> I (in SCN4; complete loss of activity;
FT dbSNP:rs1373865222)"
FT /evidence="ECO:0000269|PubMed:25492228"
FT /id="VAR_073175"
FT VARIANT 116
FT /note="M -> K (in SCN4; the patient also carries mutation
FT Thr-166 in ELANE; complete loss of activity)"
FT /evidence="ECO:0000269|PubMed:20220065,
FT ECO:0000269|PubMed:22050868, ECO:0000269|PubMed:25492228"
FT /id="VAR_064508"
FT VARIANT 116
FT /note="M -> T (in SCN4; complete loss of activity)"
FT /evidence="ECO:0000269|PubMed:23298686,
FT ECO:0000269|PubMed:25492228"
FT /id="VAR_072756"
FT VARIANT 116
FT /note="M -> V (in DURSS and SCN4; complete loss of
FT activity; dbSNP:rs267606834)"
FT /evidence="ECO:0000269|PubMed:20799326,
FT ECO:0000269|PubMed:25492228"
FT /id="VAR_064509"
FT VARIANT 118
FT /note="T -> R (in SCN4; complete loss of activity;
FT dbSNP:rs766706036)"
FT /evidence="ECO:0000269|PubMed:25492228"
FT /id="VAR_073176"
FT VARIANT 139
FT /note="S -> I (in SCN4; partial loss of activity)"
FT /evidence="ECO:0000269|PubMed:22050868,
FT ECO:0000269|PubMed:25492228"
FT /id="VAR_072757"
FT VARIANT 154
FT /note="L -> P (in SCN4; complete loss of activity)"
FT /evidence="ECO:0000269|PubMed:23018568,
FT ECO:0000269|PubMed:25492228"
FT /id="VAR_072758"
FT VARIANT 161
FT /note="R -> Q (in SCN4; complete loss of activity;
FT dbSNP:rs1485073209)"
FT /evidence="ECO:0000269|PubMed:22050868,
FT ECO:0000269|PubMed:25492228"
FT /id="VAR_073177"
FT VARIANT 185
FT /note="L -> P (in SCN4; complete loss of activity;
FT dbSNP:rs118203969)"
FT /evidence="ECO:0000269|PubMed:19118303,
FT ECO:0000269|PubMed:25492228"
FT /id="VAR_055156"
FT VARIANT 189
FT /note="R -> Q (in SCN4; partial loss of activity;
FT dbSNP:rs140294222)"
FT /evidence="ECO:0000269|PubMed:20220065,
FT ECO:0000269|PubMed:25492228"
FT /id="VAR_064510"
FT VARIANT 208
FT /note="L -> R (in SCN4; complete loss of activity)"
FT /evidence="ECO:0000269|PubMed:22469094,
FT ECO:0000269|PubMed:25492228"
FT /id="VAR_072759"
FT VARIANT 216
FT /note="T -> I (in dbSNP:rs34406052)"
FT /id="VAR_043378"
FT VARIANT 253
FT /note="R -> C (in SCN4; dbSNP:rs765927570)"
FT /evidence="ECO:0000269|PubMed:23298686"
FT /id="VAR_073178"
FT VARIANT 253
FT /note="R -> H (in SCN4; complete loss of activity;
FT peripheral-blood patient neutrophils have an increased rate
FT of spontaneous apoptosis; transmission electron microscopy
FT of patient bone marrow cells shows an enlarged rough
FT endoplasmic reticulum in myeloid progenitor cells
FT consistent with increased ER stress; dbSNP:rs118203968)"
FT /evidence="ECO:0000269|PubMed:19118303,
FT ECO:0000269|PubMed:22050868, ECO:0000269|PubMed:25492228"
FT /id="VAR_055157"
FT VARIANT 260
FT /note="G -> D (in SCN4; complete loss of activity)"
FT /evidence="ECO:0000269|PubMed:22050868,
FT ECO:0000269|PubMed:25492228"
FT /id="VAR_072760"
FT VARIANT 260
FT /note="G -> R (in SCN4; complete loss of activity;
FT dbSNP:rs200478425)"
FT /evidence="ECO:0000269|PubMed:20220065,
FT ECO:0000269|PubMed:20616219, ECO:0000269|PubMed:22050868,
FT ECO:0000269|PubMed:25492228"
FT /id="VAR_064511"
FT VARIANT 262
FT /note="G -> R (in SCN4; dbSNP:rs118203971)"
FT /evidence="ECO:0000269|PubMed:19118303"
FT /id="VAR_055158"
FT VARIANT 325
FT /note="L -> R (in SCN4)"
FT /evidence="ECO:0000269|PubMed:24105461"
FT /id="VAR_072761"
FT MUTAGEN 79
FT /note="R->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:13129915"
FT MUTAGEN 114
FT /note="H->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:13129915"
FT MUTAGEN 167
FT /note="H->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:13129915"
SQ SEQUENCE 346 AA; 38735 MW; 55C1F322E59C8439 CRC64;
MESTLGAGIV IAEALQNQLA WLENVWLWIT FLGDPKILFL FYFPAAYYAS RRVGIAVLWI
SLITEWLNLI FKWFLFGDRP FWWVHESGYY SQAPAQVHQF PSSCETGPGS PSGHCMITGA
ALWPIMTALS SQVATRARSR WVRVMPSLAY CTFLLAVGLS RIFILAHFPH QVLAGLITGA
VLGWLMTPRV PMERELSFYG LTALALMLGT SLIYWTLFTL GLDLSWSISL AFKWCERPEW
IHVDSRPFAS LSRDSGAALG LGIALHSPCY AQVRRAQLGN GQKIACLVLA MGLLGPLDWL
GHPPQISLFY IFNFLKYTLW PCLVLALVPW AVHMFSAQEA PPIHSS
