CL004_HUMAN
ID CL004_HUMAN Reviewed; 552 AA.
AC Q9NQ89; D3DUQ8; Q6MZH5;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Protein C12orf4;
GN Name=C12orf4;
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 [MRNA].
RC TISSUE=Retina;
RX PubMed=11062477; DOI=10.1038/81664;
RA White K.E., Evans W.E., O'Riordan J.L.H., Speer M.C., Econs M.J.,
RA Lorenz-Depiereux B., Grabowski M., Meitinger T., Strom T.M.;
RT "Autosomal dominant hypophosphataemic rickets is associated with mutations
RT in FGF23.";
RL Nat. Genet. 26:345-348(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver, and Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
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 [5]
RP INVOLVEMENT IN MRT66.
RX PubMed=25558065; DOI=10.1016/j.celrep.2014.12.015;
RA Alazami A.M., Patel N., Shamseldin H.E., Anazi S., Al-Dosari M.S.,
RA Alzahrani F., Hijazi H., Alshammari M., Aldahmesh M.A., Salih M.A.,
RA Faqeih E., Alhashem A., Bashiri F.A., Al-Owain M., Kentab A.Y., Sogaty S.,
RA Al Tala S., Temsah M.H., Tulbah M., Aljelaify R.F., Alshahwan S.A.,
RA Seidahmed M.Z., Alhadid A.A., Aldhalaan H., Alqallaf F., Kurdi W.,
RA Alfadhel M., Babay Z., Alsogheer M., Kaya N., Al-Hassnan Z.N.,
RA Abdel-Salam G.M., Al-Sannaa N., Al Mutairi F., El Khashab H.Y., Bohlega S.,
RA Jia X., Nguyen H.C., Hammami R., Adly N., Mohamed J.Y., Abdulwahab F.,
RA Ibrahim N., Naim E.A., Al-Younes B., Meyer B.F., Hashem M., Shaheen R.,
RA Xiong Y., Abouelhoda M., Aldeeri A.A., Monies D.M., Alkuraya F.S.;
RT "Accelerating novel candidate gene discovery in neurogenetic disorders via
RT whole-exome sequencing of prescreened multiplex consanguineous families.";
RL Cell Rep. 10:148-161(2015).
RN [6]
RP INVOLVEMENT IN MRT66, AND VARIANT MRT66 PRO-328.
RX PubMed=27311568; DOI=10.1111/cge.12821;
RA Philips A.K., Pinelli M., de Bie C.I., Mustonen A., Maeaettae T.,
RA Arts H.H., Wu K., Roepman R., Moilanen J.S., Raza S., Varilo T., Scala G.,
RA Cocozza S., Gilissen C., van Gassen K.L., Jaervelae I.;
RT "Identification of C12orf4 as a gene for autosomal recessive intellectual
RT disability.";
RL Clin. Genet. 91:100-105(2017).
RN [7]
RP INVOLVEMENT IN MRT66, AND VARIANT MRT66 454-ARG--HIS-552 DEL.
RX PubMed=28097321; DOI=10.1001/jamapsychiatry.2016.3798;
RA Reuter M.S., Tawamie H., Buchert R., Hosny Gebril O., Froukh T., Thiel C.,
RA Uebe S., Ekici A.B., Krumbiegel M., Zweier C., Hoyer J., Eberlein K.,
RA Bauer J., Scheller U., Strom T.M., Hoffjan S., Abdelraouf E.R.,
RA Meguid N.A., Abboud A., Al Khateeb M.A., Fakher M., Hamdan S., Ismael A.,
RA Muhammad S., Abdallah E., Sticht H., Wieczorek D., Reis A., Abou Jamra R.;
RT "Diagnostic yield and novel candidate genes by exome sequencing in 152
RT consanguineous families with neurodevelopmental disorders.";
RL JAMA Psychiatry 74:293-299(2017).
CC -!- FUNCTION: Plays a role in mast cell degranulation.
CC {ECO:0000250|UniProtKB:D4A770}.
CC -!- INTERACTION:
CC Q9NQ89; P55212: CASP6; NbExp=3; IntAct=EBI-11090973, EBI-718729;
CC Q9NQ89; P30519: HMOX2; NbExp=3; IntAct=EBI-11090973, EBI-712096;
CC Q9NQ89; P13473-2: LAMP2; NbExp=3; IntAct=EBI-11090973, EBI-21591415;
CC Q9NQ89; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-11090973, EBI-5280197;
CC Q9NQ89; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-11090973, EBI-2623095;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:D4A770}.
CC -!- DISEASE: Intellectual developmental disorder, autosomal recessive 66
CC (MRT66) [MIM:618221]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period. MRT66
CC patients have intellectual disability, delayed speech development,
CC neuropsychiatric symptoms, and relatively normal life span.
CC {ECO:0000269|PubMed:25558065, ECO:0000269|PubMed:27311568,
CC ECO:0000269|PubMed:28097321}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; AJ272205; CAC01126.1; -; mRNA.
DR EMBL; AL834377; CAD39040.1; -; mRNA.
DR EMBL; BX641128; CAE46058.1; -; mRNA.
DR EMBL; CH471116; EAW88845.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88846.1; -; Genomic_DNA.
DR EMBL; BC016908; AAH16908.1; -; mRNA.
DR CCDS; CCDS8528.1; -.
DR RefSeq; NP_001291740.1; NM_001304811.1.
DR RefSeq; NP_065107.1; NM_020374.3.
DR AlphaFoldDB; Q9NQ89; -.
DR SMR; Q9NQ89; -.
DR BioGRID; 121368; 18.
DR IntAct; Q9NQ89; 13.
DR STRING; 9606.ENSP00000261250; -.
DR iPTMnet; Q9NQ89; -.
DR PhosphoSitePlus; Q9NQ89; -.
DR BioMuta; C12orf4; -.
DR DMDM; 71153007; -.
DR EPD; Q9NQ89; -.
DR jPOST; Q9NQ89; -.
DR MassIVE; Q9NQ89; -.
DR MaxQB; Q9NQ89; -.
DR PaxDb; Q9NQ89; -.
DR PeptideAtlas; Q9NQ89; -.
DR PRIDE; Q9NQ89; -.
DR ProteomicsDB; 82107; -.
DR Antibodypedia; 41818; 82 antibodies from 15 providers.
DR DNASU; 57102; -.
DR Ensembl; ENST00000261250.8; ENSP00000261250.3; ENSG00000047621.12.
DR Ensembl; ENST00000545746.5; ENSP00000439996.1; ENSG00000047621.12.
DR GeneID; 57102; -.
DR KEGG; hsa:57102; -.
DR MANE-Select; ENST00000261250.8; ENSP00000261250.3; NM_020374.4; NP_065107.1.
DR UCSC; uc001qms.4; human.
DR CTD; 57102; -.
DR DisGeNET; 57102; -.
DR GeneCards; C12orf4; -.
DR HGNC; HGNC:1184; C12orf4.
DR HPA; ENSG00000047621; Low tissue specificity.
DR MalaCards; C12orf4; -.
DR MIM; 616082; gene.
DR MIM; 618221; phenotype.
DR neXtProt; NX_Q9NQ89; -.
DR OpenTargets; ENSG00000047621; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR PharmGKB; PA25505; -.
DR VEuPathDB; HostDB:ENSG00000047621; -.
DR eggNOG; KOG4506; Eukaryota.
DR GeneTree; ENSGT00390000010229; -.
DR HOGENOM; CLU_036084_0_0_1; -.
DR InParanoid; Q9NQ89; -.
DR OMA; EMASWGG; -.
DR OrthoDB; 743423at2759; -.
DR PhylomeDB; Q9NQ89; -.
DR TreeFam; TF314243; -.
DR PathwayCommons; Q9NQ89; -.
DR SignaLink; Q9NQ89; -.
DR BioGRID-ORCS; 57102; 20 hits in 1059 CRISPR screens.
DR ChiTaRS; C12orf4; human.
DR GenomeRNAi; 57102; -.
DR Pharos; Q9NQ89; Tdark.
DR PRO; PR:Q9NQ89; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9NQ89; protein.
DR Bgee; ENSG00000047621; Expressed in tendon of biceps brachii and 201 other tissues.
DR ExpressionAtlas; Q9NQ89; baseline and differential.
DR Genevisible; Q9NQ89; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0043304; P:regulation of mast cell degranulation; ISS:UniProtKB.
DR InterPro; IPR019311; DUF2362.
DR PANTHER; PTHR16525; PTHR16525; 1.
DR Pfam; PF10154; DUF2362; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Disease variant; Intellectual disability; Reference proteome.
FT CHAIN 1..552
FT /note="Protein C12orf4"
FT /id="PRO_0000089842"
FT REGION 383..403
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 328
FT /note="L -> P (in MRT66; dbSNP:rs1468772495)"
FT /evidence="ECO:0000269|PubMed:27311568"
FT /id="VAR_081778"
FT VARIANT 454..552
FT /note="Missing (in MRT66)"
FT /evidence="ECO:0000269|PubMed:28097321"
FT /id="VAR_081779"
FT CONFLICT 24
FT /note="Q -> R (in Ref. 2; CAE46058)"
FT /evidence="ECO:0000305"
FT CONFLICT 156
FT /note="I -> V (in Ref. 2; CAE46058)"
FT /evidence="ECO:0000305"
FT CONFLICT 165
FT /note="K -> E (in Ref. 2; CAE46058)"
FT /evidence="ECO:0000305"
FT CONFLICT 245
FT /note="E -> G (in Ref. 2; CAE46058)"
FT /evidence="ECO:0000305"
FT CONFLICT 377
FT /note="T -> P (in Ref. 2; CAE46058)"
FT /evidence="ECO:0000305"
FT CONFLICT 465
FT /note="I -> V (in Ref. 2; CAE46058)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 552 AA; 63801 MW; E183A979E3BA0F5E CRC64;
MKKNRERFCN REREFVYKFK VGSQCLELRV PLKFPVQENA SHLHGRLMLL HSLPCFIEKD
LKEALTQFIE EESLSDYDRD AEASLAAVKS GEVDLHQLAS TWAKAYAETT LEHARPEEPS
WDEDFADVYH DLIHSPASET LLNLEHNYFV SISELIGERD VELKKLRERQ GIEMEKVMQE
LGKSLTDQDV NSLAAQHFES QQDLENKWSN ELKQSTAIQK QEYQEWVIKL HQDLKNPNNS
SLSEEIKVQP SQFRESVEAI GRIYEEQRKL EESFTIHLGA QLKTMHNLRL LRADMLDFCK
HKRNHRSGVK LHRLQTALSL YSTSLCGLVL LVDNRINSYS GIKRDFATVC QECTDFHFPR
IEEQLEVVQQ VVLYARTQRR SKLKESLDSG NQNGGNDDKT KNAERNYLNV LPGEFYITRH
SNLSEIHVAF HLCVDDHVKS GNITARDPAI MGLRNILKVC CTHDITTISI PLLLVHDMSE
EMTIPWCLRR AELVFKCVKG FMMEMASWDG GISRTVQFLV PQSISEEMFY QLSNMLPQIF
RVSSTLTLTS KH
