NOGG_HUMAN
ID NOGG_HUMAN Reviewed; 232 AA.
AC Q13253;
DT 14-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Noggin;
DE Flags: Precursor;
GN Name=NOG;
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 [GENOMIC DNA].
RC TISSUE=Placenta, and Temporal cortex;
RX PubMed=7666191; DOI=10.1523/jneurosci.15-09-06077.1995;
RA Valenzuela D.M., Economides A.N., Rojas E., Lamb T.M., Nunez L., Jones P.,
RA Ip N.Y., Espinosa R. III, Brannan C.I., Gilbert D.J., Copeland N.G.,
RA Jenkins N.A., Le Beau M.M., Harland R.M., Yancopoulos G.D.;
RT "Identification of mammalian noggin and its expression in the adult nervous
RT system.";
RL J. Neurosci. 15:6077-6084(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 INTERACTION WITH GDF5, AND FUNCTION.
RX PubMed=21976273; DOI=10.1002/jbmr.532;
RA Schwaerzer G.K., Hiepen C., Schrewe H., Nickel J., Ploeger F., Sebald W.,
RA Mueller T., Knaus P.;
RT "New insights into the molecular mechanism of multiple synostoses syndrome
RT (SYNS): mutation within the GDF5 knuckle epitope causes noggin-
RT resistance.";
RL J. Bone Miner. Res. 27:429-442(2012).
RN [4]
RP INTERACTION WITH GDF5.
RX PubMed=24098149; DOI=10.1371/journal.pgen.1003846;
RA Degenkolbe E., Konig J., Zimmer J., Walther M., Reissner C., Nickel J.,
RA Ploger F., Raspopovic J., Sharpe J., Dathe K., Hecht J.T., Mundlos S.,
RA Doelken S.C., Seemann P.;
RT "A GDF5 point mutation strikes twice--causing BDA1 and SYNS2.";
RL PLoS Genet. 9:E1003846-E1003846(2013).
RN [5]
RP FUNCTION.
RX PubMed=26643732; DOI=10.1002/jbmr.2761;
RA Wang J., Yu T., Wang Z., Ohte S., Yao R.E., Zheng Z., Geng J., Cai H.,
RA Ge Y., Li Y., Xu Y., Zhang Q., Gusella J.F., Fu Q., Pregizer S., Rosen V.,
RA Shen Y.;
RT "A New Subtype of Multiple-Synostoses Syndrome is Caused by a Mutation in
RT GDF6 that Decreases its Sensitivity to Noggin and Enhances its Potency as a
RT BMP Signal.";
RL J. Bone Miner. Res. 31:882-889(2016).
RN [6]
RP VARIANTS LEU-83 AND MET-104.
RX PubMed=31138930; DOI=10.1038/s41436-019-0552-8;
RA Yang Y., Zheng Y., Li W., Li L., Tu M., Zhao L., Mei H., Zhu G., Zhu Y.;
RT "SMAD6 is frequently mutated in nonsyndromic radioulnar synostosis.";
RL Genet. Med. 21:2577-2585(2019).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.42 ANGSTROMS) OF 28-232 IN COMPLEX WITH BMP7,
RP FUNCTION, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=12478285; DOI=10.1038/nature01245;
RA Groppe J., Greenwald J., Wiater E., Rodriguez-Leon J., Economides A.N.,
RA Kwiatkowski W., Affolter M., Vale W.W., Izpisua Belmonte J.C., Choe S.;
RT "Structural basis of BMP signalling inhibition by the cystine knot protein
RT Noggin.";
RL Nature 420:636-642(2002).
RN [8]
RP VARIANTS SYM1A ARG-35; CYS-189; ASN-220; CYS-222; ASP-222 AND LEU-223, AND
RP VARIANT SYNS1 GLY-217.
RX PubMed=10080184; DOI=10.1038/6821;
RA Gong Y., Krakow D., Marcelino J., Wilkin D., Chitayat D., Babul-Hirji R.,
RA Hudgins L., Cremers C.W., Cremers F.P.M., Brunner H.G., Reinker K.,
RA Rimoin D.L., Cohn D.H., Goodman F.R., Reardon W., Patton M.,
RA Francomano C.A., Warman M.L.;
RT "Heterozygous mutations in the gene encoding noggin affect human joint
RT morphogenesis.";
RL Nat. Genet. 21:302-304(1999).
RN [9]
RP VARIANT SYM1A TYR-184.
RX PubMed=11846737; DOI=10.1034/j.1399-0004.2001.600607.x;
RA Takahashi T., Takahashi I., Komatsu M., Sawaishi Y., Higashi K.,
RA Nishimura G., Saito H., Takada G.;
RT "Mutations of the NOG gene in individuals with proximal symphalangism and
RT multiple synostosis syndrome.";
RL Clin. Genet. 60:447-451(2001).
RN [10]
RP VARIANTS TCC ARG-35; LEU-204 AND CYS-222.
RX PubMed=11545688; DOI=10.1097/00125817-200109000-00004;
RA Dixon M.E., Armstrong P., Stevens D.B., Bamshad M.;
RT "Identical mutations in NOG can cause either tarsal/carpal coalition
RT syndrome or proximal symphalangism.";
RL Genet. Med. 3:349-353(2001).
RN [11]
RP INVOLVEMENT IN SABTS.
RX PubMed=12089654; DOI=10.1086/342067;
RA Brown D.J., Kim T.B., Petty E.M., Downs C.A., Martin D.M., Strouse P.J.,
RA Moroi S.E., Milunsky J.M., Lesperance M.M.;
RT "Autosomal dominant stapes ankylosis with broad thumbs and toes, hyperopia,
RT and skeletal anomalies is caused by heterozygous nonsense and frameshift
RT mutations in NOG, the gene encoding noggin.";
RL Am. J. Hum. Genet. 71:618-624(2002).
RN [12]
RP VARIANT SYM1A SER-35.
RX PubMed=11857750; DOI=10.1002/humu.9016.abs;
RA Mangino M., Flex E., Digilio M.C., Giannotti A., Dallapiccola B.;
RT "Identification of a novel NOG gene mutation (P35S) in an Italian family
RT with symphalangism.";
RL Hum. Mutat. 19:308-308(2002).
RN [13]
RP VARIANT SYM1A CYS-205.
RX PubMed=15770128; DOI=10.1097/00019605-200504000-00004;
RA van den Ende J.J., Mattelaer P., Declau F., Vanhoenacker F., Claes J.,
RA Van Hul E., Baten E.;
RT "The facio-audio-symphalangism syndrome in a four generation family with a
RT nonsense mutation in the NOG-gene.";
RL Clin. Dysmorphol. 14:73-80(2005).
RN [14]
RP VARIANTS BDB2 ALA-35; SER-35; PRO-36; LYS-48; GLY-167 AND SER-187.
RX PubMed=17668388; DOI=10.1086/519697;
RA Lehmann K., Seemann P., Silan F., Goecke T.O., Irgang S., Kjaer K.W.,
RA Kjaergaard S., Mahoney M.J., Morlot S., Reissner C., Kerr B.,
RA Wilkie A.O.M., Mundlos S.;
RT "A new subtype of brachydactyly type B caused by point mutations in the
RT bone morphogenetic protein antagonist NOGGIN.";
RL Am. J. Hum. Genet. 81:388-396(2007).
RN [15]
RP VARIANT SYNS1 TRP-232.
RX PubMed=20503332; DOI=10.1002/ajmg.a.33387;
RA Rudnik-Schoneborn S., Takahashi T., Busse S., Schmidt T., Senderek J.,
RA Eggermann T., Zerres K.;
RT "Facioaudiosymphalangism syndrome and growth acceleration associated with a
RT heterozygous NOG mutation.";
RL Am. J. Med. Genet. A 152:1540-1544(2010).
CC -!- FUNCTION: Inhibitor of bone morphogenetic proteins (BMP) signaling
CC which is required for growth and patterning of the neural tube and
CC somite. Essential for cartilage morphogenesis and joint formation.
CC Inhibits chondrocyte differentiation through its interaction with GDF5
CC and, probably, GDF6 (PubMed:21976273, PubMed:26643732).
CC {ECO:0000269|PubMed:12478285, ECO:0000269|PubMed:21976273,
CC ECO:0000269|PubMed:26643732}.
CC -!- SUBUNIT: Homodimer. Interacts with GDF5; inhibits chondrocyte
CC differentiation. {ECO:0000269|PubMed:12478285,
CC ECO:0000269|PubMed:21976273, ECO:0000269|PubMed:24098149}.
CC -!- INTERACTION:
CC Q13253; P12643: BMP2; NbExp=2; IntAct=EBI-1035205, EBI-1029262;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- DISEASE: Symphalangism, proximal 1A (SYM1A) [MIM:185800]: A disease
CC characterized by the hereditary absence of the proximal interphalangeal
CC joints. Distal interphalangeal joints are less frequently involved and
CC metacarpophalangeal joints are rarely affected whereas carpal bone
CC malformation and fusion are common. In the lower extremities, tarsal
CC bone coalition is common. Conductive hearing loss is seen and is due to
CC fusion of the stapes to the petrous part of the temporal bone.
CC {ECO:0000269|PubMed:10080184, ECO:0000269|PubMed:11846737,
CC ECO:0000269|PubMed:11857750, ECO:0000269|PubMed:15770128}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Multiple synostoses syndrome 1 (SYNS1) [MIM:186500]: A bone
CC disease characterized by multiple progressive joint fusions that
CC commonly involve proximal interphalangeal, tarsal-carpal, humeroradial
CC and cervical spine joints. Additional features can include progressive
CC conductive deafness and facial dysmorphism.
CC {ECO:0000269|PubMed:10080184, ECO:0000269|PubMed:20503332}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Tarsal-carpal coalition syndrome (TCC) [MIM:186570]: Autosomal
CC dominant disorder characterized by fusion of the carpals, tarsals and
CC phalanges, short first metacarpals causing brachydactyly, and
CC humeroradial fusion. TCC is allelic to SYM1, and different mutations in
CC NOG can result in either TCC or SYM1 in different families.
CC {ECO:0000269|PubMed:11545688}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Stapes ankylosis with broad thumb and toes (SABTS)
CC [MIM:184460]: An autosomal dominant disorder characterized by
CC hyperopia, a hemicylindrical nose, broad thumbs, great toes, and other
CC minor skeletal anomalies but lacked carpal and tarsal fusion and
CC symphalangism. {ECO:0000269|PubMed:12089654}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Brachydactyly B2 (BDB2) [MIM:611377]: A form of brachydactyly
CC characterized by hypoplasia/aplasia of distal phalanges in combination
CC with distal symphalangism, fusion of carpal/tarsal bones and partial
CC cutaneous syndactyly. {ECO:0000269|PubMed:17668388}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the noggin family. {ECO:0000305}.
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DR EMBL; U31202; AAA83259.1; -; Genomic_DNA.
DR EMBL; BC034027; AAH34027.1; -; mRNA.
DR CCDS; CCDS11589.1; -.
DR RefSeq; NP_005441.1; NM_005450.4.
DR PDB; 1M4U; X-ray; 2.42 A; A=28-232.
DR PDB; 7AG0; X-ray; 3.10 A; A=28-232.
DR PDBsum; 1M4U; -.
DR PDBsum; 7AG0; -.
DR AlphaFoldDB; Q13253; -.
DR SMR; Q13253; -.
DR BioGRID; 114668; 43.
DR IntAct; Q13253; 3.
DR MINT; Q13253; -.
DR STRING; 9606.ENSP00000328181; -.
DR GlyGen; Q13253; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q13253; -.
DR PhosphoSitePlus; Q13253; -.
DR BioMuta; NOG; -.
DR DMDM; 15214099; -.
DR MassIVE; Q13253; -.
DR PaxDb; Q13253; -.
DR PeptideAtlas; Q13253; -.
DR PRIDE; Q13253; -.
DR ProteomicsDB; 59253; -.
DR Antibodypedia; 3149; 561 antibodies from 35 providers.
DR DNASU; 9241; -.
DR Ensembl; ENST00000332822.6; ENSP00000328181.4; ENSG00000183691.6.
DR GeneID; 9241; -.
DR KEGG; hsa:9241; -.
DR MANE-Select; ENST00000332822.6; ENSP00000328181.4; NM_005450.6; NP_005441.1.
DR UCSC; uc002iup.2; human.
DR CTD; 9241; -.
DR DisGeNET; 9241; -.
DR GeneCards; NOG; -.
DR HGNC; HGNC:7866; NOG.
DR HPA; ENSG00000183691; Tissue enhanced (brain, placenta).
DR MalaCards; NOG; -.
DR MIM; 184460; phenotype.
DR MIM; 185800; phenotype.
DR MIM; 186500; phenotype.
DR MIM; 186570; phenotype.
DR MIM; 602991; gene.
DR MIM; 611377; phenotype.
DR neXtProt; NX_Q13253; -.
DR OpenTargets; ENSG00000183691; -.
DR Orphanet; 140908; Brachydactyly type B2.
DR Orphanet; 3237; Multiple synostoses syndrome.
DR Orphanet; 3250; Proximal symphalangism.
DR Orphanet; 140917; Stapes ankylosis with broad thumbs and toes.
DR Orphanet; 1412; Tarsal-carpal coalition syndrome.
DR PharmGKB; PA31670; -.
DR VEuPathDB; HostDB:ENSG00000183691; -.
DR eggNOG; KOG4485; Eukaryota.
DR GeneTree; ENSGT00390000006009; -.
DR HOGENOM; CLU_085186_1_0_1; -.
DR InParanoid; Q13253; -.
DR OMA; FCPVVYA; -.
DR OrthoDB; 1391421at2759; -.
DR PhylomeDB; Q13253; -.
DR TreeFam; TF353745; -.
DR PathwayCommons; Q13253; -.
DR Reactome; R-HSA-201451; Signaling by BMP.
DR SignaLink; Q13253; -.
DR SIGNOR; Q13253; -.
DR BioGRID-ORCS; 9241; 14 hits in 1073 CRISPR screens.
DR ChiTaRS; NOG; human.
DR EvolutionaryTrace; Q13253; -.
DR GeneWiki; Noggin_(protein); -.
DR GenomeRNAi; 9241; -.
DR Pharos; Q13253; Tbio.
DR PRO; PR:Q13253; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q13253; protein.
DR Bgee; ENSG00000183691; Expressed in pigmented layer of retina and 95 other tissues.
DR Genevisible; Q13253; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0019955; F:cytokine binding; IPI:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0055009; P:atrial cardiac muscle tissue morphogenesis; ISS:BHF-UCL.
DR GO; GO:0048318; P:axial mesoderm development; IEA:Ensembl.
DR GO; GO:0061312; P:BMP signaling pathway involved in heart development; ISS:BHF-UCL.
DR GO; GO:0051216; P:cartilage development; IEA:UniProtKB-KW.
DR GO; GO:0021533; P:cell differentiation in hindbrain; IMP:BHF-UCL.
DR GO; GO:1904888; P:cranial skeletal system development; IEA:Ensembl.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IDA:BHF-UCL.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IMP:BHF-UCL.
DR GO; GO:0060272; P:embryonic skeletal joint morphogenesis; IMP:BHF-UCL.
DR GO; GO:0048706; P:embryonic skeletal system development; IMP:BHF-UCL.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISS:BHF-UCL.
DR GO; GO:0001706; P:endoderm formation; IEA:Ensembl.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0035640; P:exploration behavior; IEA:Ensembl.
DR GO; GO:0060325; P:face morphogenesis; IEA:Ensembl.
DR GO; GO:0060825; P:fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation; IMP:BHF-UCL.
DR GO; GO:0061384; P:heart trabecula morphogenesis; ISS:BHF-UCL.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0060173; P:limb development; IMP:BHF-UCL.
DR GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:0060425; P:lung morphogenesis; IEA:Ensembl.
DR GO; GO:0003149; P:membranous septum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
DR GO; GO:0042474; P:middle ear morphogenesis; IMP:BHF-UCL.
DR GO; GO:0008045; P:motor neuron axon guidance; IEA:Ensembl.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0048712; P:negative regulation of astrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IDA:BHF-UCL.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:BHF-UCL.
DR GO; GO:0060044; P:negative regulation of cardiac muscle cell proliferation; ISS:UniProtKB.
DR GO; GO:0061037; P:negative regulation of cartilage development; IEA:Ensembl.
DR GO; GO:0030336; P:negative regulation of cell migration; IDA:BHF-UCL.
DR GO; GO:0060302; P:negative regulation of cytokine activity; IDA:BHF-UCL.
DR GO; GO:1905006; P:negative regulation of epithelial to mesenchymal transition involved in endocardial cushion formation; ISS:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IDA:BHF-UCL.
DR GO; GO:0060394; P:negative regulation of pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0001839; P:neural plate morphogenesis; IEA:Ensembl.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0048570; P:notochord morphogenesis; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISS:BHF-UCL.
DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; ISS:BHF-UCL.
DR GO; GO:0021983; P:pituitary gland development; IEA:Ensembl.
DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:BHF-UCL.
DR GO; GO:0090193; P:positive regulation of glomerulus development; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; IEA:Ensembl.
DR GO; GO:0060513; P:prostatic bud formation; IEA:Ensembl.
DR GO; GO:2000313; P:regulation of fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation; IMP:BHF-UCL.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IEA:Ensembl.
DR GO; GO:1990926; P:short-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IMP:BHF-UCL.
DR GO; GO:0061053; P:somite development; IEA:Ensembl.
DR GO; GO:0021510; P:spinal cord development; IEA:Ensembl.
DR GO; GO:0048863; P:stem cell differentiation; IEA:Ensembl.
DR GO; GO:0060676; P:ureteric bud formation; IEA:Ensembl.
DR GO; GO:0003223; P:ventricular compact myocardium morphogenesis; ISS:BHF-UCL.
DR GO; GO:0060412; P:ventricular septum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0008542; P:visual learning; IEA:Ensembl.
DR GO; GO:0042060; P:wound healing; ISS:UniProtKB.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR008717; Noggin.
DR PANTHER; PTHR10494; PTHR10494; 1.
DR PIRSF; PIRSF008129; Noggin; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chondrogenesis; Deafness; Developmental protein;
KW Differentiation; Disease variant; Disulfide bond; Glycoprotein;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..232
FT /note="Noggin"
FT /id="PRO_0000019813"
FT REGION 77..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 62
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 155..192
FT /evidence="ECO:0000269|PubMed:12478285"
FT DISULFID 178..228
FT /evidence="ECO:0000269|PubMed:12478285"
FT DISULFID 184..230
FT /evidence="ECO:0000269|PubMed:12478285"
FT DISULFID 207..215
FT /evidence="ECO:0000269|PubMed:12478285"
FT VARIANT 35
FT /note="P -> A (in BDB2; dbSNP:rs28937580)"
FT /evidence="ECO:0000269|PubMed:17668388"
FT /id="VAR_036997"
FT VARIANT 35
FT /note="P -> R (in SYM1A and TCC; dbSNP:rs104894611)"
FT /evidence="ECO:0000269|PubMed:10080184,
FT ECO:0000269|PubMed:11545688"
FT /id="VAR_011361"
FT VARIANT 35
FT /note="P -> S (in SYM1A and BDB2; dbSNP:rs28937580)"
FT /evidence="ECO:0000269|PubMed:11857750,
FT ECO:0000269|PubMed:17668388"
FT /id="VAR_018324"
FT VARIANT 36
FT /note="A -> P (in BDB2)"
FT /evidence="ECO:0000269|PubMed:17668388"
FT /id="VAR_036998"
FT VARIANT 48
FT /note="E -> K (in BDB2)"
FT /evidence="ECO:0000269|PubMed:17668388"
FT /id="VAR_036999"
FT VARIANT 83
FT /note="P -> L (found in a family with radioulnar
FT synostosis; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:31138930"
FT /id="VAR_084488"
FT VARIANT 104
FT /note="L -> M (found in a case of radioulnar synostosis;
FT unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:31138930"
FT /id="VAR_084489"
FT VARIANT 167
FT /note="R -> G (in BDB2; dbSNP:rs121908949)"
FT /evidence="ECO:0000269|PubMed:17668388"
FT /id="VAR_037000"
FT VARIANT 184
FT /note="C -> Y (in SYM1A; sporadic; de novo mutation;
FT dbSNP:rs104894612)"
FT /evidence="ECO:0000269|PubMed:11846737"
FT /id="VAR_018325"
FT VARIANT 187
FT /note="P -> S (in BDB2)"
FT /evidence="ECO:0000269|PubMed:17668388"
FT /id="VAR_037001"
FT VARIANT 189
FT /note="G -> C (in SYM1A; dbSNP:rs104894609)"
FT /evidence="ECO:0000269|PubMed:10080184"
FT /id="VAR_011362"
FT VARIANT 204
FT /note="R -> L (in TCC; dbSNP:rs104894610)"
FT /evidence="ECO:0000269|PubMed:11545688"
FT /id="VAR_018326"
FT VARIANT 205
FT /note="W -> C (in SYM1A; dbSNP:rs104894615)"
FT /evidence="ECO:0000269|PubMed:15770128"
FT /id="VAR_037605"
FT VARIANT 217
FT /note="W -> G (in SYNS1; dbSNP:rs104894603)"
FT /evidence="ECO:0000269|PubMed:10080184"
FT /id="VAR_011363"
FT VARIANT 220
FT /note="I -> N (in SYM1A)"
FT /evidence="ECO:0000269|PubMed:10080184"
FT /id="VAR_011364"
FT VARIANT 222
FT /note="Y -> C (in SYM1A and TCC; dbSNP:rs104894602)"
FT /evidence="ECO:0000269|PubMed:10080184,
FT ECO:0000269|PubMed:11545688"
FT /id="VAR_011365"
FT VARIANT 222
FT /note="Y -> D (in SYM1A; dbSNP:rs121908948)"
FT /evidence="ECO:0000269|PubMed:10080184"
FT /id="VAR_011366"
FT VARIANT 223
FT /note="P -> L (in SYM1A; dbSNP:rs104894608)"
FT /evidence="ECO:0000269|PubMed:10080184"
FT /id="VAR_011367"
FT VARIANT 232
FT /note="C -> W (in SYNS1; dbSNP:rs387906844)"
FT /evidence="ECO:0000269|PubMed:20503332"
FT /id="VAR_064541"
FT STRAND 29..32
FT /evidence="ECO:0007829|PDB:1M4U"
FT HELIX 58..60
FT /evidence="ECO:0007829|PDB:1M4U"
FT HELIX 63..70
FT /evidence="ECO:0007829|PDB:1M4U"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:1M4U"
FT TURN 76..78
FT /evidence="ECO:0007829|PDB:1M4U"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:1M4U"
FT HELIX 99..109
FT /evidence="ECO:0007829|PDB:1M4U"
FT HELIX 118..121
FT /evidence="ECO:0007829|PDB:1M4U"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:1M4U"
FT HELIX 139..153
FT /evidence="ECO:0007829|PDB:1M4U"
FT STRAND 158..163
FT /evidence="ECO:0007829|PDB:1M4U"
FT STRAND 168..177
FT /evidence="ECO:0007829|PDB:1M4U"
FT STRAND 185..188
FT /evidence="ECO:0007829|PDB:1M4U"
FT STRAND 191..207
FT /evidence="ECO:0007829|PDB:1M4U"
FT HELIX 210..212
FT /evidence="ECO:0007829|PDB:1M4U"
FT STRAND 214..231
FT /evidence="ECO:0007829|PDB:1M4U"
SQ SEQUENCE 232 AA; 25774 MW; FCA0D8E1E2098580 CRC64;
MERCPSLGVT LYALVVVLGL RATPAGGQHY LHIRPAPSDN LPLVDLIEHP DPIFDPKEKD
LNETLLRSLL GGHYDPGFMA TSPPEDRPGG GGGAAGGAED LAELDQLLRQ RPSGAMPSEI
KGLEFSEGLA QGKKQRLSKK LRRKLQMWLW SQTFCPVLYA WNDLGSRFWP RYVKVGSCFS
KRSCSVPEGM VCKPSKSVHL TVLRWRCQRR GGQRCGWIPI QYPIISECKC SC
