Full text data of NEUROG3
NEUROG3
(ATOH5, BHLHA7, NGN3)
[Confidence: low (only semi-automatic identification from reviews)]
Neurogenin-3; NGN-3 (Class A basic helix-loop-helix protein 7; bHLHa7; Protein atonal homolog 5)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Neurogenin-3; NGN-3 (Class A basic helix-loop-helix protein 7; bHLHa7; Protein atonal homolog 5)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9Y4Z2
ID NGN3_HUMAN Reviewed; 214 AA.
AC Q9Y4Z2; Q5VVI0; Q6DJX6; Q9BY24;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-MAY-2009, sequence version 2.
DT 22-JAN-2014, entry version 105.
DE RecName: Full=Neurogenin-3;
DE Short=NGN-3;
DE AltName: Full=Class A basic helix-loop-helix protein 7;
DE Short=bHLHa7;
DE AltName: Full=Protein atonal homolog 5;
GN Name=NEUROG3; Synonyms=ATOH5, BHLHA7, NGN3;
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 [GENOMIC DNA], AND VARIANT SER-199.
RA Ravassard P., Icard-Liepkalns C., Wiard L., Julien J.P., Mallet J.;
RT "The human neurogenin 3 homolog maps to chromosome 10q21.3 and its
RT expression pattern is identical to that of its murine counterparts.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-199.
RA del Bosque-Plata L., Lin J., Horikawa Y., Schwarz P.E.H., Cox N.J.,
RA Iwasaki N., Iwamoto Y., German M., Bell G.;
RT "Beta-cell transcription factors and diabetes: no evidence for
RT diabetes-associated mutations in the coding region of the proendocrine
RT neurogenin 3 gene (NEUROG3) in Japanese patients with MODY.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Rectum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-199.
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 [7]
RP VARIANTS DIAR4 LEU-93 AND SER-107, AND CHARACTERIZATION OF VARIANTS
RP DIAR4 LEU-93 AND SER-107.
RX PubMed=16855267; DOI=10.1056/NEJMoa054288;
RA Wang J., Cortina G., Wu S.V., Tran R., Cho J.-H., Tsai M.-J.,
RA Bailey T.J., Jamrich M., Ament M.E., Treem W.R., Hill I.D.,
RA Vargas J.H., Gershman G., Farmer D.G., Reyen L., Martin M.G.;
RT "Mutant neurogenin-3 in congenital malabsorptive diarrhea.";
RL N. Engl. J. Med. 355:270-280(2006).
CC -!- FUNCTION: Acts as a transcriptional regulator. Together with NKX2-
CC 2, initiates transcriptional activation of NEUROD1. Involved in
CC neurogenesis. Also required for the specification of a common
CC precursor of the 4 pancreatic endocrine cell types (By
CC similarity).
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another
CC bHLH protein (By similarity).
CC -!- SUBCELLULAR LOCATION: Nucleus (Potential).
CC -!- DISEASE: Diarrhea 4, malabsorptive, congenital (DIAR4)
CC [MIM:610370]: A disease characterized by severe, life-threatening
CC watery diarrhea associated with generalized malabsorption and a
CC paucity of enteroendocrine cells. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; AJ133776; CAB45384.1; -; Genomic_DNA.
DR EMBL; AF234829; AAK15022.1; -; Genomic_DNA.
DR EMBL; AK313952; BAG36669.1; -; mRNA.
DR EMBL; AL450311; CAH72729.1; -; Genomic_DNA.
DR EMBL; CH471083; EAW54328.1; -; Genomic_DNA.
DR EMBL; BC074938; AAH74938.1; -; mRNA.
DR EMBL; BC074939; AAH74939.1; -; mRNA.
DR EMBL; BC117488; AAI17489.1; -; mRNA.
DR EMBL; BC126468; AAI26469.1; -; mRNA.
DR RefSeq; NP_066279.2; NM_020999.3.
DR UniGene; Hs.532682; -.
DR ProteinModelPortal; Q9Y4Z2; -.
DR SMR; Q9Y4Z2; 83-140.
DR STRING; 9606.ENSP00000242462; -.
DR PhosphoSite; Q9Y4Z2; -.
DR DMDM; 229462908; -.
DR PaxDb; Q9Y4Z2; -.
DR PRIDE; Q9Y4Z2; -.
DR DNASU; 50674; -.
DR Ensembl; ENST00000242462; ENSP00000242462; ENSG00000122859.
DR GeneID; 50674; -.
DR KEGG; hsa:50674; -.
DR UCSC; uc001jpp.3; human.
DR CTD; 50674; -.
DR GeneCards; GC10M071331; -.
DR H-InvDB; HIX0035408; -.
DR HGNC; HGNC:13806; NEUROG3.
DR HPA; HPA039785; -.
DR MIM; 604882; gene.
DR MIM; 610370; phenotype.
DR neXtProt; NX_Q9Y4Z2; -.
DR Orphanet; 83620; Congenital malabsorptive diarrhea due to paucity of enteroendocrine cells.
DR PharmGKB; PA31571; -.
DR eggNOG; NOG327835; -.
DR HOGENOM; HOG000063655; -.
DR HOVERGEN; HBG031743; -.
DR InParanoid; Q9Y4Z2; -.
DR KO; K08028; -.
DR OMA; RKKANDR; -.
DR OrthoDB; EOG7TTQB1; -.
DR PhylomeDB; Q9Y4Z2; -.
DR Reactome; REACT_111045; Developmental Biology.
DR GeneWiki; NEUROG3; -.
DR GenomeRNAi; 50674; -.
DR NextBio; 53214; -.
DR PRO; PR:Q9Y4Z2; -.
DR ArrayExpress; Q9Y4Z2; -.
DR Bgee; Q9Y4Z2; -.
DR CleanEx; HS_NEUROG3; -.
DR Genevestigator; Q9Y4Z2; -.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003690; F:double-stranded DNA binding; IEA:Ensembl.
DR GO; GO:0001077; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription; IEA:Ensembl.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR GO; GO:0031018; P:endocrine pancreas development; TAS:Reactome.
DR GO; GO:0030855; P:epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR GO; GO:0030902; P:hindbrain development; IEA:Ensembl.
DR GO; GO:0007422; P:peripheral nervous system development; TAS:ProtInc.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0021510; P:spinal cord development; IEA:Ensembl.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Activator; Complete proteome; Developmental protein; Differentiation;
KW Disease mutation; DNA-binding; Neurogenesis; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1 214 Neurogenin-3.
FT /FTId=PRO_0000127402.
FT DOMAIN 83 135 bHLH.
FT VARIANT 93 93 R -> L (in DIAR4; attenuated NEUROG3
FT function in vivo).
FT /FTId=VAR_029003.
FT VARIANT 107 107 R -> S (in DIAR4; attenuated NEUROG3
FT function in vivo).
FT /FTId=VAR_029004.
FT VARIANT 199 199 F -> S (in dbSNP:rs4536103).
FT /FTId=VAR_055316.
FT CONFLICT 43 43 R -> P (in Ref. 1; CAB45384).
FT CONFLICT 98 98 N -> D (in Ref. 1; CAB45384).
FT CONFLICT 165 165 S -> P (in Ref. 1; CAB45384).
SQ SEQUENCE 214 AA; 23077 MW; 2E80623E46F88B83 CRC64;
MTPQPSGAPT VQVTRETERS FPRASEDEVT CPTSAPPSPT RTRGNCAEAE EGGCRGAPRK
LRARRGGRSR PKSELALSKQ RRSRRKKAND RERNRMHNLN SALDALRGVL PTFPDDAKLT
KIETLRFAHN YIWALTQTLR IADHSLYALE PPAPHCGELG SPGGSPGDWG SLYSPVSQAG
SLSPAASLEE RPGLLGATFS ACLSPGSLAF SDFL
//
ID NGN3_HUMAN Reviewed; 214 AA.
AC Q9Y4Z2; Q5VVI0; Q6DJX6; Q9BY24;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-MAY-2009, sequence version 2.
DT 22-JAN-2014, entry version 105.
DE RecName: Full=Neurogenin-3;
DE Short=NGN-3;
DE AltName: Full=Class A basic helix-loop-helix protein 7;
DE Short=bHLHa7;
DE AltName: Full=Protein atonal homolog 5;
GN Name=NEUROG3; Synonyms=ATOH5, BHLHA7, NGN3;
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 [GENOMIC DNA], AND VARIANT SER-199.
RA Ravassard P., Icard-Liepkalns C., Wiard L., Julien J.P., Mallet J.;
RT "The human neurogenin 3 homolog maps to chromosome 10q21.3 and its
RT expression pattern is identical to that of its murine counterparts.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-199.
RA del Bosque-Plata L., Lin J., Horikawa Y., Schwarz P.E.H., Cox N.J.,
RA Iwasaki N., Iwamoto Y., German M., Bell G.;
RT "Beta-cell transcription factors and diabetes: no evidence for
RT diabetes-associated mutations in the coding region of the proendocrine
RT neurogenin 3 gene (NEUROG3) in Japanese patients with MODY.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Rectum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-199.
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 [7]
RP VARIANTS DIAR4 LEU-93 AND SER-107, AND CHARACTERIZATION OF VARIANTS
RP DIAR4 LEU-93 AND SER-107.
RX PubMed=16855267; DOI=10.1056/NEJMoa054288;
RA Wang J., Cortina G., Wu S.V., Tran R., Cho J.-H., Tsai M.-J.,
RA Bailey T.J., Jamrich M., Ament M.E., Treem W.R., Hill I.D.,
RA Vargas J.H., Gershman G., Farmer D.G., Reyen L., Martin M.G.;
RT "Mutant neurogenin-3 in congenital malabsorptive diarrhea.";
RL N. Engl. J. Med. 355:270-280(2006).
CC -!- FUNCTION: Acts as a transcriptional regulator. Together with NKX2-
CC 2, initiates transcriptional activation of NEUROD1. Involved in
CC neurogenesis. Also required for the specification of a common
CC precursor of the 4 pancreatic endocrine cell types (By
CC similarity).
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another
CC bHLH protein (By similarity).
CC -!- SUBCELLULAR LOCATION: Nucleus (Potential).
CC -!- DISEASE: Diarrhea 4, malabsorptive, congenital (DIAR4)
CC [MIM:610370]: A disease characterized by severe, life-threatening
CC watery diarrhea associated with generalized malabsorption and a
CC paucity of enteroendocrine cells. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain.
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DR EMBL; AJ133776; CAB45384.1; -; Genomic_DNA.
DR EMBL; AF234829; AAK15022.1; -; Genomic_DNA.
DR EMBL; AK313952; BAG36669.1; -; mRNA.
DR EMBL; AL450311; CAH72729.1; -; Genomic_DNA.
DR EMBL; CH471083; EAW54328.1; -; Genomic_DNA.
DR EMBL; BC074938; AAH74938.1; -; mRNA.
DR EMBL; BC074939; AAH74939.1; -; mRNA.
DR EMBL; BC117488; AAI17489.1; -; mRNA.
DR EMBL; BC126468; AAI26469.1; -; mRNA.
DR RefSeq; NP_066279.2; NM_020999.3.
DR UniGene; Hs.532682; -.
DR ProteinModelPortal; Q9Y4Z2; -.
DR SMR; Q9Y4Z2; 83-140.
DR STRING; 9606.ENSP00000242462; -.
DR PhosphoSite; Q9Y4Z2; -.
DR DMDM; 229462908; -.
DR PaxDb; Q9Y4Z2; -.
DR PRIDE; Q9Y4Z2; -.
DR DNASU; 50674; -.
DR Ensembl; ENST00000242462; ENSP00000242462; ENSG00000122859.
DR GeneID; 50674; -.
DR KEGG; hsa:50674; -.
DR UCSC; uc001jpp.3; human.
DR CTD; 50674; -.
DR GeneCards; GC10M071331; -.
DR H-InvDB; HIX0035408; -.
DR HGNC; HGNC:13806; NEUROG3.
DR HPA; HPA039785; -.
DR MIM; 604882; gene.
DR MIM; 610370; phenotype.
DR neXtProt; NX_Q9Y4Z2; -.
DR Orphanet; 83620; Congenital malabsorptive diarrhea due to paucity of enteroendocrine cells.
DR PharmGKB; PA31571; -.
DR eggNOG; NOG327835; -.
DR HOGENOM; HOG000063655; -.
DR HOVERGEN; HBG031743; -.
DR InParanoid; Q9Y4Z2; -.
DR KO; K08028; -.
DR OMA; RKKANDR; -.
DR OrthoDB; EOG7TTQB1; -.
DR PhylomeDB; Q9Y4Z2; -.
DR Reactome; REACT_111045; Developmental Biology.
DR GeneWiki; NEUROG3; -.
DR GenomeRNAi; 50674; -.
DR NextBio; 53214; -.
DR PRO; PR:Q9Y4Z2; -.
DR ArrayExpress; Q9Y4Z2; -.
DR Bgee; Q9Y4Z2; -.
DR CleanEx; HS_NEUROG3; -.
DR Genevestigator; Q9Y4Z2; -.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003690; F:double-stranded DNA binding; IEA:Ensembl.
DR GO; GO:0001077; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription; IEA:Ensembl.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR GO; GO:0031018; P:endocrine pancreas development; TAS:Reactome.
DR GO; GO:0030855; P:epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR GO; GO:0030902; P:hindbrain development; IEA:Ensembl.
DR GO; GO:0007422; P:peripheral nervous system development; TAS:ProtInc.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0021510; P:spinal cord development; IEA:Ensembl.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Activator; Complete proteome; Developmental protein; Differentiation;
KW Disease mutation; DNA-binding; Neurogenesis; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1 214 Neurogenin-3.
FT /FTId=PRO_0000127402.
FT DOMAIN 83 135 bHLH.
FT VARIANT 93 93 R -> L (in DIAR4; attenuated NEUROG3
FT function in vivo).
FT /FTId=VAR_029003.
FT VARIANT 107 107 R -> S (in DIAR4; attenuated NEUROG3
FT function in vivo).
FT /FTId=VAR_029004.
FT VARIANT 199 199 F -> S (in dbSNP:rs4536103).
FT /FTId=VAR_055316.
FT CONFLICT 43 43 R -> P (in Ref. 1; CAB45384).
FT CONFLICT 98 98 N -> D (in Ref. 1; CAB45384).
FT CONFLICT 165 165 S -> P (in Ref. 1; CAB45384).
SQ SEQUENCE 214 AA; 23077 MW; 2E80623E46F88B83 CRC64;
MTPQPSGAPT VQVTRETERS FPRASEDEVT CPTSAPPSPT RTRGNCAEAE EGGCRGAPRK
LRARRGGRSR PKSELALSKQ RRSRRKKAND RERNRMHNLN SALDALRGVL PTFPDDAKLT
KIETLRFAHN YIWALTQTLR IADHSLYALE PPAPHCGELG SPGGSPGDWG SLYSPVSQAG
SLSPAASLEE RPGLLGATFS ACLSPGSLAF SDFL
//
MIM
604882
*RECORD*
*FIELD* NO
604882
*FIELD* TI
*604882 NEUROGENIN 3; NEUROG3
;;NGN3;;
ATOH5
*FIELD* TX
DESCRIPTION
Neurogenin-3 (NEUROG3) is expressed in endocrine progenitor cells and is
read morerequired for endocrine cell development in the pancreas and intestine
(Wang et al., 2006). It belongs to a family of basic helix-loop-helix
transcription factors involved in the determination of neural precursor
cells in the neuroectoderm (Gradwohl et al., 2000).
CLONING
By in situ hybridization, Sommer et al. (1996) found that mouse Ngn3 was
most strongly expressed in a restricted region of the developing spinal
cord, just dorsal to the floor plate. Expression was detectable as early
as embryonic day 9 and persisted until day 14. Ngn3 was also expressed
in the developing hypothalamic region and in pancreatic islet cell
progenitors.
GENE STRUCTURE
Sommer et al. (1996) determined that the mouse Ngn3 gene contains a
single coding exon.
GENE FUNCTION
Spence et al. (2011) established a robust and efficient process to
direct the differentiation of human pluripotent stem cells into
intestinal tissue in vitro using a temporal series of growth factor
manipulations to mimic embryonic intestinal development. Using this
culture system as a model to study human intestinal development, Spence
et al. (2011) identified that the combined activity of WNT3A (606359)
and FGF4 (164980) is required for hindgut specification, whereas FGF4
alone is sufficient to promote hindgut morphogenesis. Spence et al.
(2011) also determined that NEUROG3 is both necessary and sufficient for
human enteroendocrine cell development in vitro. Spence et al. (2011)
concluded that human intestinal stem cells form de novo during
development.
Talchai et al. (2012) showed that, unexpectedly, somatic ablation of
Foxo1 (136533) in Neurog3+ enteroendocrine progenitor cells gives rise
to gut insulin-positive cells that express markers of mature beta cells
and secrete bioactive insulin as well as C peptide in response to
glucose and sulfonylureas. Lineage tracing experiments showed that gut
insulin-positive cells arise cell autonomously from Foxo1-deficient
cells. Inducible Fox1 ablation in adult mice also resulted in the
generation of gut insulin-positive cells. Following ablation by the
beta-cell toxin streptozotocin, gut insulin-positive cells regenerated
and produced insulin, reversing hyperglycemia in mice. Talchai et al.
(2012) concluded that their data indicated that Neurog3+ enteroendocrine
progenitors require active Foxo1 to prevent differentiation into
insulin-positive cells, and suggested that Foxo1 ablation in gut
epithelium may provide an approach to restore insulin production in type
1 diabetes.
MOLECULAR GENETICS
Kim et al. (2001) concluded that genetic variability in neurogenin-3
gene does not contribute to the etiology of maturity-onset diabetes of
the young (see 125853) or other forms of autosomal dominant diabetes.
In 3 unrelated boys with congenital malabsorptive diarrhea (DIAR4;
610370), Wang et al. (2006) identified 2 different homozygous mutations
in the NEUROG3 gene (604882.0001; 604882.0002). Both mutations rendered
the NEUROG3 protein unable to activate NEUROD1 (601724), a downstream
target of NEUROG3, and compromised the ability of NEUROG3 to bind to an
E-box element in the NEUROD1 promoter. The injection of wildtype but not
mutant NEUROG3 mRNA into Xenopus embryos induced NEUROD1 expression. The
authors referred to the disorder in these boys as 'enteric
anendocrinosis.'
ANIMAL MODEL
Mouse Ngn3 is expressed in discrete regions of the nervous system and in
scattered cells in the embryonic pancreas (Sommer et al., 1996).
Gradwohl et al. (2000) showed that Ngn3-positive cells did not express
insulin or glucagon, suggesting that Ngn3 marks early precursors of
pancreatic endocrine cells. Mice lacking Ngn3 function failed to
generate any pancreatic endocrine cells and died postnatally from
diabetes. Expression of the pancreatic transcription factors Isl1
(600366), Pax4 (167413), Pax6 (607108), and NeuroD (601724) was lost,
and endocrine precursors were lacking in the mutant pancreatic
epithelium. Thus, Ngn3 was required for the specification of a common
precursor of the 4 pancreatic endocrine cell types.
Lee et al. (2002) found that glucagon-secreting A cells,
somatostatin-secreting D cells, and gastrin-secreting G cells were
absent from the epithelium of the glandular stomach of Ngn3 -/- mice,
and the number of serotonin-expressing enterochromaffin cells was
dramatically decreased. In addition, Ngn3 -/- mice displayed intestinal
metaplasia of the gastric epithelium. Lee et al. (2002) concluded that
NGN3 is required for differentiation of enteroendocrine cells in the
stomach and maintenance of gastric epithelial cell identity.
Zhou et al. (2008) used a strategy of reexpressing key developmental
regulators in vivo to identify a specific combination of 3 transcription
factors, Neurog3, Pdx1 (600733), and Mafa (610303), that reprogrammed
differentiated pancreatic exocrine cells in adult mice into cells that
closely resembled beta cells. Induced beta cells were indistinguishable
from endogenous islet beta cells in size, shape, and ultrastructure.
They expressed genes essential for beta cell function and could
ameliorate hyperglycemia by remodeling local vasculature and secreting
insulin. Zhou et al. (2008) concluded that their study provided an
example of cellular reprogramming using defined factors in an adult
organ and suggested a general paradigm for directing cell reprogramming
without reversion to a pluripotent stem cell state.
*FIELD* AV
.0001
DIARRHEA 4, MALABSORPTIVE, CONGENITAL
NEUROG3, ARG107SER
In a patient with congenital malabsorptive diarrhea (610370), Wang et
al. (2006) identified a homozygous missense mutation in the neurogenin-3
gene, predicted to result in an arg107-to-ser (R107S) substitution in
the first helix of the protein, which is critical for the activation of
downstream genes. The mutation was not identified in 100 control
individuals.
.0002
DIARRHEA 4, MALABSORPTIVE, CONGENITAL
NEUROG3, ARG93LEU
In 2 presumably unrelated males with congenital malabsorptive diarrhea
(610370), Wang et al. (2006) identified a homozygous mutation in the
NEUROG3 gene, resulting in an arg93-to-leu (R93L) substitution in the
DNA-binding domain just upstream of the first helix. The mutation was
not identified in 100 control individuals.
*FIELD* RF
1. Gradwohl, G.; Dierich, A.; LeMeur, M.; Guillemot, F.: Neurogenin3
is required for the development of the four endocrine cell lineages
of the pancreas. Proc. Nat. Acad. Sci. 97: 1607-1611, 2000.
2. Kim, S.-H.; Warram, J. H.; Krolewski, A. S.; Doria, A.: Mutation
screening of the neurogenin-3 gene in autosomal dominant diabetes. J.
Clin. Endocr. Metab. 86: 2320-2322, 2001.
3. Lee, C. S.; Perreault, N.; Brestelli, J. E.; Kaestner, K. H.:
Neurogenin 3 is essential for the proper specification of gastric
enteroendocrine cells and the maintenance of gastric epithelial cell
identity. Genes Dev. 16: 1488-1497, 2002.
4. Sommer, L.; Ma, Q.; Anderson, D. J.: neurogenins, a novel family
of atonal-related bHLH transcription factors, are putative mammalian
neuronal determination genes that reveal progenitor cell heterogeneity
in the developing CNS and PNS. Molec. Cell. Neurosci. 8: 221-241,
1996.
5. Sommer, L.; Ma, Q.; Anderson, D. J.: Neurogenins, a novel family
of atonal-related bHLH transcription factors, are putative mammalian
neuronal determination genes that reveal progenitor cell heterogeneity
in the developing CNS and PNS. Molec. Cell. Neurosci. 8: 221-241,
1996.
6. Spence, J. R.; Mayhew, C. N.; Rankin, S. A.; Kuhar, M. F.; Vallance,
J. E.; Tolle, K.; Hoskins, E. E.; Kalinichenko, V. V.; Wells, S. I.;
Zorn, A. M.; Shroyer, N. F.; Wells, J. M.: Directed differentiation
of human pluripotent stem cells into intestinal tissue in vitro. Nature 470:
105-109, 2011.
7. Talchai, C.; Xuan, S.; Kitamura, T.; DePinho, R. A.; Accili, D.
: Generation of functional insulin-producing cells in the gut by Foxo1
ablation. Nature Genet. 44: 406-412, 2012.
8. Wang, J.; Cortina, G.; Wu, S. V.; Tran, R.; Cho, J.-H.; Tsai, M.-J.;
Bailey, T. J.; Jamrich, M.; Ament, M. E.; Treem, W. R.; Hill, I. D.;
Vargas, J. H.; Gershman, G.; Farmer, D. G.; Reyen, L.; Martin, M.
G.: Mutant neurogenin-3 in congenital malabsorptive diarrhea. New
Eng. J. Med. 355: 270-280, 2006.
9. Zhou, Q.; Brown, J.; Kanarek, A.; Rajagopal, J.; Melton, D. A.
: In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455:
627-632, 2008.
*FIELD* CN
Ada Hamosh - updated: 7/24/2012
Ada Hamosh - updated: 6/10/2011
Ada Hamosh - updated: 11/5/2008
Patricia A. Hartz - updated: 10/12/2006
Victor A. McKusick - updated: 8/9/2006
Patricia A. Hartz - updated: 7/25/2005
John A. Phillips, III - updated: 10/3/2001
*FIELD* CD
Victor A. McKusick: 4/27/2000
*FIELD* ED
alopez: 07/31/2012
terry: 7/24/2012
alopez: 6/22/2011
terry: 6/10/2011
alopez: 11/18/2008
terry: 11/5/2008
alopez: 10/17/2006
terry: 10/12/2006
carol: 9/5/2006
ckniffin: 9/1/2006
terry: 8/9/2006
mgross: 7/29/2005
terry: 7/25/2005
ckniffin: 8/27/2002
carol: 6/27/2002
cwells: 10/8/2001
cwells: 10/3/2001
carol: 11/29/2000
mcapotos: 9/8/2000
carol: 4/27/2000
*RECORD*
*FIELD* NO
604882
*FIELD* TI
*604882 NEUROGENIN 3; NEUROG3
;;NGN3;;
ATOH5
*FIELD* TX
DESCRIPTION
Neurogenin-3 (NEUROG3) is expressed in endocrine progenitor cells and is
read morerequired for endocrine cell development in the pancreas and intestine
(Wang et al., 2006). It belongs to a family of basic helix-loop-helix
transcription factors involved in the determination of neural precursor
cells in the neuroectoderm (Gradwohl et al., 2000).
CLONING
By in situ hybridization, Sommer et al. (1996) found that mouse Ngn3 was
most strongly expressed in a restricted region of the developing spinal
cord, just dorsal to the floor plate. Expression was detectable as early
as embryonic day 9 and persisted until day 14. Ngn3 was also expressed
in the developing hypothalamic region and in pancreatic islet cell
progenitors.
GENE STRUCTURE
Sommer et al. (1996) determined that the mouse Ngn3 gene contains a
single coding exon.
GENE FUNCTION
Spence et al. (2011) established a robust and efficient process to
direct the differentiation of human pluripotent stem cells into
intestinal tissue in vitro using a temporal series of growth factor
manipulations to mimic embryonic intestinal development. Using this
culture system as a model to study human intestinal development, Spence
et al. (2011) identified that the combined activity of WNT3A (606359)
and FGF4 (164980) is required for hindgut specification, whereas FGF4
alone is sufficient to promote hindgut morphogenesis. Spence et al.
(2011) also determined that NEUROG3 is both necessary and sufficient for
human enteroendocrine cell development in vitro. Spence et al. (2011)
concluded that human intestinal stem cells form de novo during
development.
Talchai et al. (2012) showed that, unexpectedly, somatic ablation of
Foxo1 (136533) in Neurog3+ enteroendocrine progenitor cells gives rise
to gut insulin-positive cells that express markers of mature beta cells
and secrete bioactive insulin as well as C peptide in response to
glucose and sulfonylureas. Lineage tracing experiments showed that gut
insulin-positive cells arise cell autonomously from Foxo1-deficient
cells. Inducible Fox1 ablation in adult mice also resulted in the
generation of gut insulin-positive cells. Following ablation by the
beta-cell toxin streptozotocin, gut insulin-positive cells regenerated
and produced insulin, reversing hyperglycemia in mice. Talchai et al.
(2012) concluded that their data indicated that Neurog3+ enteroendocrine
progenitors require active Foxo1 to prevent differentiation into
insulin-positive cells, and suggested that Foxo1 ablation in gut
epithelium may provide an approach to restore insulin production in type
1 diabetes.
MOLECULAR GENETICS
Kim et al. (2001) concluded that genetic variability in neurogenin-3
gene does not contribute to the etiology of maturity-onset diabetes of
the young (see 125853) or other forms of autosomal dominant diabetes.
In 3 unrelated boys with congenital malabsorptive diarrhea (DIAR4;
610370), Wang et al. (2006) identified 2 different homozygous mutations
in the NEUROG3 gene (604882.0001; 604882.0002). Both mutations rendered
the NEUROG3 protein unable to activate NEUROD1 (601724), a downstream
target of NEUROG3, and compromised the ability of NEUROG3 to bind to an
E-box element in the NEUROD1 promoter. The injection of wildtype but not
mutant NEUROG3 mRNA into Xenopus embryos induced NEUROD1 expression. The
authors referred to the disorder in these boys as 'enteric
anendocrinosis.'
ANIMAL MODEL
Mouse Ngn3 is expressed in discrete regions of the nervous system and in
scattered cells in the embryonic pancreas (Sommer et al., 1996).
Gradwohl et al. (2000) showed that Ngn3-positive cells did not express
insulin or glucagon, suggesting that Ngn3 marks early precursors of
pancreatic endocrine cells. Mice lacking Ngn3 function failed to
generate any pancreatic endocrine cells and died postnatally from
diabetes. Expression of the pancreatic transcription factors Isl1
(600366), Pax4 (167413), Pax6 (607108), and NeuroD (601724) was lost,
and endocrine precursors were lacking in the mutant pancreatic
epithelium. Thus, Ngn3 was required for the specification of a common
precursor of the 4 pancreatic endocrine cell types.
Lee et al. (2002) found that glucagon-secreting A cells,
somatostatin-secreting D cells, and gastrin-secreting G cells were
absent from the epithelium of the glandular stomach of Ngn3 -/- mice,
and the number of serotonin-expressing enterochromaffin cells was
dramatically decreased. In addition, Ngn3 -/- mice displayed intestinal
metaplasia of the gastric epithelium. Lee et al. (2002) concluded that
NGN3 is required for differentiation of enteroendocrine cells in the
stomach and maintenance of gastric epithelial cell identity.
Zhou et al. (2008) used a strategy of reexpressing key developmental
regulators in vivo to identify a specific combination of 3 transcription
factors, Neurog3, Pdx1 (600733), and Mafa (610303), that reprogrammed
differentiated pancreatic exocrine cells in adult mice into cells that
closely resembled beta cells. Induced beta cells were indistinguishable
from endogenous islet beta cells in size, shape, and ultrastructure.
They expressed genes essential for beta cell function and could
ameliorate hyperglycemia by remodeling local vasculature and secreting
insulin. Zhou et al. (2008) concluded that their study provided an
example of cellular reprogramming using defined factors in an adult
organ and suggested a general paradigm for directing cell reprogramming
without reversion to a pluripotent stem cell state.
*FIELD* AV
.0001
DIARRHEA 4, MALABSORPTIVE, CONGENITAL
NEUROG3, ARG107SER
In a patient with congenital malabsorptive diarrhea (610370), Wang et
al. (2006) identified a homozygous missense mutation in the neurogenin-3
gene, predicted to result in an arg107-to-ser (R107S) substitution in
the first helix of the protein, which is critical for the activation of
downstream genes. The mutation was not identified in 100 control
individuals.
.0002
DIARRHEA 4, MALABSORPTIVE, CONGENITAL
NEUROG3, ARG93LEU
In 2 presumably unrelated males with congenital malabsorptive diarrhea
(610370), Wang et al. (2006) identified a homozygous mutation in the
NEUROG3 gene, resulting in an arg93-to-leu (R93L) substitution in the
DNA-binding domain just upstream of the first helix. The mutation was
not identified in 100 control individuals.
*FIELD* RF
1. Gradwohl, G.; Dierich, A.; LeMeur, M.; Guillemot, F.: Neurogenin3
is required for the development of the four endocrine cell lineages
of the pancreas. Proc. Nat. Acad. Sci. 97: 1607-1611, 2000.
2. Kim, S.-H.; Warram, J. H.; Krolewski, A. S.; Doria, A.: Mutation
screening of the neurogenin-3 gene in autosomal dominant diabetes. J.
Clin. Endocr. Metab. 86: 2320-2322, 2001.
3. Lee, C. S.; Perreault, N.; Brestelli, J. E.; Kaestner, K. H.:
Neurogenin 3 is essential for the proper specification of gastric
enteroendocrine cells and the maintenance of gastric epithelial cell
identity. Genes Dev. 16: 1488-1497, 2002.
4. Sommer, L.; Ma, Q.; Anderson, D. J.: neurogenins, a novel family
of atonal-related bHLH transcription factors, are putative mammalian
neuronal determination genes that reveal progenitor cell heterogeneity
in the developing CNS and PNS. Molec. Cell. Neurosci. 8: 221-241,
1996.
5. Sommer, L.; Ma, Q.; Anderson, D. J.: Neurogenins, a novel family
of atonal-related bHLH transcription factors, are putative mammalian
neuronal determination genes that reveal progenitor cell heterogeneity
in the developing CNS and PNS. Molec. Cell. Neurosci. 8: 221-241,
1996.
6. Spence, J. R.; Mayhew, C. N.; Rankin, S. A.; Kuhar, M. F.; Vallance,
J. E.; Tolle, K.; Hoskins, E. E.; Kalinichenko, V. V.; Wells, S. I.;
Zorn, A. M.; Shroyer, N. F.; Wells, J. M.: Directed differentiation
of human pluripotent stem cells into intestinal tissue in vitro. Nature 470:
105-109, 2011.
7. Talchai, C.; Xuan, S.; Kitamura, T.; DePinho, R. A.; Accili, D.
: Generation of functional insulin-producing cells in the gut by Foxo1
ablation. Nature Genet. 44: 406-412, 2012.
8. Wang, J.; Cortina, G.; Wu, S. V.; Tran, R.; Cho, J.-H.; Tsai, M.-J.;
Bailey, T. J.; Jamrich, M.; Ament, M. E.; Treem, W. R.; Hill, I. D.;
Vargas, J. H.; Gershman, G.; Farmer, D. G.; Reyen, L.; Martin, M.
G.: Mutant neurogenin-3 in congenital malabsorptive diarrhea. New
Eng. J. Med. 355: 270-280, 2006.
9. Zhou, Q.; Brown, J.; Kanarek, A.; Rajagopal, J.; Melton, D. A.
: In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455:
627-632, 2008.
*FIELD* CN
Ada Hamosh - updated: 7/24/2012
Ada Hamosh - updated: 6/10/2011
Ada Hamosh - updated: 11/5/2008
Patricia A. Hartz - updated: 10/12/2006
Victor A. McKusick - updated: 8/9/2006
Patricia A. Hartz - updated: 7/25/2005
John A. Phillips, III - updated: 10/3/2001
*FIELD* CD
Victor A. McKusick: 4/27/2000
*FIELD* ED
alopez: 07/31/2012
terry: 7/24/2012
alopez: 6/22/2011
terry: 6/10/2011
alopez: 11/18/2008
terry: 11/5/2008
alopez: 10/17/2006
terry: 10/12/2006
carol: 9/5/2006
ckniffin: 9/1/2006
terry: 8/9/2006
mgross: 7/29/2005
terry: 7/25/2005
ckniffin: 8/27/2002
carol: 6/27/2002
cwells: 10/8/2001
cwells: 10/3/2001
carol: 11/29/2000
mcapotos: 9/8/2000
carol: 4/27/2000
MIM
610370
*RECORD*
*FIELD* NO
610370
*FIELD* TI
#610370 DIARRHEA 4, MALABSORPTIVE, CONGENITAL; DIAR4
;;ENTERIC ANENDOCRINOSIS
*FIELD* TX
read moreA number sign (#) is used with this entry because this form of
congenital malabsorptive diarrhea, referred to here as DIAR4, is caused
by mutation in the gene encoding neurogenin-3 (NEUROG3; 604882) on
chromosome 10q21.3.
For a discussion of phenotypic and genetic heterogeneity of congenital
diarrhea, see DIAR1 (214700).
CLINICAL FEATURES
Wang et al. (2006) reported 3 unrelated boys who presented with chronic
unremitting malabsorptive diarrhea in the first weeks of life.
Accompanying features included vomiting, dehydration, and severe
hyperchloremic metabolic acidosis after the ingestion of standard
cows-milk-based formula. The diarrhea ceased during periods of fasting,
but returned with glucose- or amino acid-based oral solutions. All
studies were negative for allergic, immunologic, infectious, and
metabolic causes of diarrhea; pancreatic exocrine function was also
normal. The children were discharged on parenteral nutrition and limited
enteral feeding. One child died of sepsis at about 3 years of age; the
other 2 continued to have large-volume loose stools daily and low
weight. Both children developed type I diabetes (IDDM; 222100) at age 8
years. Small bowel biopsies showed normal villus structure and profound
dysgenesis of the enteroendocrine cells. Only a few intestinal
enteroendocrine cells stained positive for chromogranin A (CHGA;
118910); normal numbers of Paneth, goblet, and absorptive cells were
observed. Wang et al. (2006) referred to the disorder as 'enteric
anendocrinosis.'
MOLECULAR GENETICS
In 3 unrelated boys with congenital malabsorptive diarrhea, Wang et al.
(2006) identified 2 different homozygous mutations in the NEUROG3 gene
(604882.0001; 604882.0002).
*FIELD* RF
1. Wang, J.; Cortina, G.; Wu, S. V.; Tran, R.; Cho, J.-H.; Tsai, M.-J.;
Bailey, T. J.; Jamrich, M.; Ament, M. E.; Treem, W. R.; Hill, I. D.;
Vargas, J. H.; Gershman, G.; Farmer, D. G.; Reyen, L.; Martin, M.
G.: Mutant neurogenin-3 in congenital malabsorptive diarrhea. New
Eng. J. Med. 355: 270-280, 2006.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Weight];
Low weight;
[Other];
Failure to thrive
ABDOMEN:
[Gastrointestinal];
Diarrhea, malabsorptive, severe;
Vomiting;
Dysgenesis of enteroendocrine cells in the small and large bowel mucosa
ENDOCRINE FEATURES:
Type 1 diabetes mellitus developed in some patients
METABOLIC FEATURES:
Hyperchloremic metabolic acidosis;
Dehydration
MISCELLANEOUS:
Onset in first weeks of life
MOLECULAR BASIS:
Caused by mutation in the neurogenin 3 gene (NEUROG3, 604882.0001)
*FIELD* CD
Cassandra L. Kniffin: 9/1/2006
*FIELD* ED
joanna: 05/22/2007
ckniffin: 9/1/2006
*FIELD* CN
Marla J. F. O'Neill - updated: 01/12/2010
*FIELD* CD
Cassandra L. Kniffin: 9/1/2006
*FIELD* ED
carol: 01/12/2010
carol: 3/26/2009
carol: 9/5/2006
ckniffin: 9/1/2006
*RECORD*
*FIELD* NO
610370
*FIELD* TI
#610370 DIARRHEA 4, MALABSORPTIVE, CONGENITAL; DIAR4
;;ENTERIC ANENDOCRINOSIS
*FIELD* TX
read moreA number sign (#) is used with this entry because this form of
congenital malabsorptive diarrhea, referred to here as DIAR4, is caused
by mutation in the gene encoding neurogenin-3 (NEUROG3; 604882) on
chromosome 10q21.3.
For a discussion of phenotypic and genetic heterogeneity of congenital
diarrhea, see DIAR1 (214700).
CLINICAL FEATURES
Wang et al. (2006) reported 3 unrelated boys who presented with chronic
unremitting malabsorptive diarrhea in the first weeks of life.
Accompanying features included vomiting, dehydration, and severe
hyperchloremic metabolic acidosis after the ingestion of standard
cows-milk-based formula. The diarrhea ceased during periods of fasting,
but returned with glucose- or amino acid-based oral solutions. All
studies were negative for allergic, immunologic, infectious, and
metabolic causes of diarrhea; pancreatic exocrine function was also
normal. The children were discharged on parenteral nutrition and limited
enteral feeding. One child died of sepsis at about 3 years of age; the
other 2 continued to have large-volume loose stools daily and low
weight. Both children developed type I diabetes (IDDM; 222100) at age 8
years. Small bowel biopsies showed normal villus structure and profound
dysgenesis of the enteroendocrine cells. Only a few intestinal
enteroendocrine cells stained positive for chromogranin A (CHGA;
118910); normal numbers of Paneth, goblet, and absorptive cells were
observed. Wang et al. (2006) referred to the disorder as 'enteric
anendocrinosis.'
MOLECULAR GENETICS
In 3 unrelated boys with congenital malabsorptive diarrhea, Wang et al.
(2006) identified 2 different homozygous mutations in the NEUROG3 gene
(604882.0001; 604882.0002).
*FIELD* RF
1. Wang, J.; Cortina, G.; Wu, S. V.; Tran, R.; Cho, J.-H.; Tsai, M.-J.;
Bailey, T. J.; Jamrich, M.; Ament, M. E.; Treem, W. R.; Hill, I. D.;
Vargas, J. H.; Gershman, G.; Farmer, D. G.; Reyen, L.; Martin, M.
G.: Mutant neurogenin-3 in congenital malabsorptive diarrhea. New
Eng. J. Med. 355: 270-280, 2006.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Weight];
Low weight;
[Other];
Failure to thrive
ABDOMEN:
[Gastrointestinal];
Diarrhea, malabsorptive, severe;
Vomiting;
Dysgenesis of enteroendocrine cells in the small and large bowel mucosa
ENDOCRINE FEATURES:
Type 1 diabetes mellitus developed in some patients
METABOLIC FEATURES:
Hyperchloremic metabolic acidosis;
Dehydration
MISCELLANEOUS:
Onset in first weeks of life
MOLECULAR BASIS:
Caused by mutation in the neurogenin 3 gene (NEUROG3, 604882.0001)
*FIELD* CD
Cassandra L. Kniffin: 9/1/2006
*FIELD* ED
joanna: 05/22/2007
ckniffin: 9/1/2006
*FIELD* CN
Marla J. F. O'Neill - updated: 01/12/2010
*FIELD* CD
Cassandra L. Kniffin: 9/1/2006
*FIELD* ED
carol: 01/12/2010
carol: 3/26/2009
carol: 9/5/2006
ckniffin: 9/1/2006