ID   ZSWM6_HUMAN             Reviewed;        1215 AA.
AC   Q9HCJ5;
DT   16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT   05-MAY-2009, sequence version 2.
DT   27-MAR-2024, entry version 137.
DE   RecName: Full=Zinc finger SWIM domain-containing protein 6;
GN   Name=ZSWIM6 {ECO:0000303|PubMed:29198722,
GN   ECO:0000312|HGNC:HGNC:29316}; Synonyms=KIAA1577;
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].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA   Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA   Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA   Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA   Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA   Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA   Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 473-1215.
RC   TISSUE=Brain;
RX   PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA   Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XVIII. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 7:273-281(2000).
RN   [3]
RP   VARIANT AFND TRP-1163.
RX   PubMed=25105228; DOI=10.1016/j.ajhg.2014.07.008;
RG   University of Washington Center for Mendelian Genomics;
RA   Smith J.D., Hing A.V., Clarke C.M., Johnson N.M., Perez F.A., Park S.S.,
RA   Horst J.A., Mecham B., Maves L., Nickerson D.A., Cunningham M.L.;
RT   "Exome Sequencing identifies a recurrent de novo ZSWIM6 mutation associated
RT   with acromelic frontonasal dysostosis.";
RL   Am. J. Hum. Genet. 95:235-240(2014).
RN   [4]
RP   VARIANT ARG-763.
RX   PubMed=26566883; DOI=10.1136/jmedgenet-2015-103179;
RA   Rafiullah R., Aslamkhan M., Paramasivam N., Thiel C., Mustafa G.,
RA   Wiemann S., Schlesner M., Wade R.C., Rappold G.A., Berkel S.;
RT   "Homozygous missense mutation in the LMAN2L gene segregates with
RT   intellectual disability in a large consanguineous Pakistani family.";
RL   J. Med. Genet. 53:138-144(2016).
RN   [5]
RP   INVOLVEMENT IN NEDMAGA, AND VARIANT NEDMAGA 913-ARG--GLY-1215 DEL.
RX   PubMed=29198722; DOI=10.1016/j.ajhg.2017.10.009;
RG   DDD Study;
RA   Palmer E.E., Kumar R., Gordon C.T., Shaw M., Hubert L., Carroll R., Rio M.,
RA   Murray L., Leffler M., Dudding-Byth T., Oufadem M., Lalani S.R.,
RA   Lewis A.M., Xia F., Tam A., Webster R., Brammah S., Filippini F.,
RA   Pollard J., Spies J., Minoche A.E., Cowley M.J., Risen S.,
RA   Powell-Hamilton N.N., Tusi J.E., Immken L., Nagakura H., Bole-Feysot C.,
RA   Nitschke P., Garrigue A., de Saint Basile G., Kivuva E., Scott R.H.,
RA   Rendon A., Munnich A., Newman W., Kerr B., Besmond C., Rosenfeld J.A.,
RA   Amiel J., Field M., Gecz J.;
RT   "A Recurrent De Novo Nonsense Variant in ZSWIM6 Results in Severe
RT   Intellectual Disability without Frontonasal or Limb Malformations.";
RL   Am. J. Hum. Genet. 101:995-1005(2017).
CC   -!- FUNCTION: involved in nervous system development, important for
CC       striatal morphology and motor regulation.
CC       {ECO:0000250|UniProtKB:Q80TB7}.
CC   -!- DISEASE: Acromelic frontonasal dysostosis (AFND) [MIM:603671]: A rare
CC       variant form of frontonasal dysplasia, an array of abnormalities
CC       affecting the eyes, forehead and nose and linked to midfacial
CC       dysraphia. The clinical picture is highly variable. Major findings
CC       include true ocular hypertelorism, broadening of the nasal root, median
CC       facial cleft affecting the nose and/or upper lip and palate, unilateral
CC       or bilateral clefting of the alae nasi, lack of formation of the nasal
CC       tip, anterior cranium bifidum occultum, a V-shaped or widow's peak
CC       frontal hairline. AFND is characterized by the association of
CC       frontonasal malformations with various combinations of polydactyly,
CC       tibial hypoplasia, epibulbar dermoid, encephalocoele, corpus callosum
CC       agenesis and Dandy-Walker malformation. {ECO:0000269|PubMed:25105228}.
CC       Note=The disease is caused by variants affecting the gene represented
CC       in this entry.
CC   -!- DISEASE: Neurodevelopmental disorder with movement abnormalities,
CC       abnormal gait, and autistic features (NEDMAGA) [MIM:617865]: An
CC       autosomal dominant neurodevelopmental disorder characterized by
CC       infantile-onset global developmental delay, severe to profound
CC       intellectual disability, mildly delayed walking with broad-based and
CC       unsteady gait, and absence of meaningful language. Patients have
CC       features of autism, with repetitive behaviors and poor communication,
CC       but usually are socially reactive and have a happy demeanor. More
CC       variable neurologic features include mild seizures, spasticity, and
CC       peripheral neuropathy. {ECO:0000269|PubMed:29198722}. Note=The disease
CC       is caused by variants affecting the gene represented in this entry.
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DR   EMBL; AC122718; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC008836; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AB046797; BAB13403.1; -; mRNA.
DR   CCDS; CCDS47215.1; -.
DR   RefSeq; NP_065979.1; NM_020928.1.
DR   AlphaFoldDB; Q9HCJ5; -.
DR   BioGRID; 121714; 7.
DR   IntAct; Q9HCJ5; 5.
DR   STRING; 9606.ENSP00000252744; -.
DR   GlyGen; Q9HCJ5; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9HCJ5; -.
DR   PhosphoSitePlus; Q9HCJ5; -.
DR   BioMuta; ZSWIM6; -.
DR   DMDM; 229462808; -.
DR   EPD; Q9HCJ5; -.
DR   MassIVE; Q9HCJ5; -.
DR   MaxQB; Q9HCJ5; -.
DR   PaxDb; 9606-ENSP00000252744; -.
DR   PeptideAtlas; Q9HCJ5; -.
DR   ProteomicsDB; 81740; -.
DR   Antibodypedia; 50791; 104 antibodies from 15 providers.
DR   DNASU; 57688; -.
DR   Ensembl; ENST00000252744.6; ENSP00000252744.5; ENSG00000130449.6.
DR   GeneID; 57688; -.
DR   KEGG; hsa:57688; -.
DR   MANE-Select; ENST00000252744.6; ENSP00000252744.5; NM_020928.2; NP_065979.1.
DR   UCSC; uc003jsr.4; human.
DR   AGR; HGNC:29316; -.
DR   CTD; 57688; -.
DR   DisGeNET; 57688; -.
DR   GeneCards; ZSWIM6; -.
DR   HGNC; HGNC:29316; ZSWIM6.
DR   HPA; ENSG00000130449; Low tissue specificity.
DR   MalaCards; ZSWIM6; -.
DR   MIM; 603671; phenotype.
DR   MIM; 615951; gene.
DR   MIM; 617865; phenotype.
DR   neXtProt; NX_Q9HCJ5; -.
DR   OpenTargets; ENSG00000130449; -.
DR   Orphanet; 1827; Acromelic frontonasal dysplasia.
DR   PharmGKB; PA134910181; -.
DR   VEuPathDB; HostDB:ENSG00000130449; -.
DR   eggNOG; KOG3615; Eukaryota.
DR   GeneTree; ENSGT00940000155496; -.
DR   HOGENOM; CLU_005301_1_0_1; -.
DR   InParanoid; Q9HCJ5; -.
DR   OMA; ACHIDDE; -.
DR   OrthoDB; 3266353at2759; -.
DR   PhylomeDB; Q9HCJ5; -.
DR   TreeFam; TF324881; -.
DR   PathwayCommons; Q9HCJ5; -.
DR   SignaLink; Q9HCJ5; -.
DR   BioGRID-ORCS; 57688; 16 hits in 1162 CRISPR screens.
DR   ChiTaRS; ZSWIM6; human.
DR   GenomeRNAi; 57688; -.
DR   Pharos; Q9HCJ5; Tbio.
DR   PRO; PR:Q9HCJ5; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; Q9HCJ5; Protein.
DR   Bgee; ENSG00000130449; Expressed in oviduct epithelium and 188 other cell types or tissues.
DR   GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; IBA:GO_Central.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0021773; P:striatal medium spiny neuron differentiation; ISS:UniProtKB.
DR   InterPro; IPR007527; Znf_SWIM.
DR   InterPro; IPR048370; ZSWIM4-8_C.
DR   PANTHER; PTHR22619; ZINC FINGER SWIM DOMAIN CONTAINING PROTEIN 4, 5, 6; 1.
DR   PANTHER; PTHR22619:SF3; ZINC FINGER SWIM DOMAIN-CONTAINING PROTEIN 6; 1.
DR   Pfam; PF21055; ZSWIM4-8_C; 1.
DR   PROSITE; PS50966; ZF_SWIM; 1.
DR   Genevisible; Q9HCJ5; HS.
PE   1: Evidence at protein level;
KW   Disease variant; Dwarfism; Intellectual disability; Metal-binding;
KW   Neurogenesis; Reference proteome; Zinc; Zinc-finger.
FT   CHAIN           1..1215
FT                   /note="Zinc finger SWIM domain-containing protein 6"
FT                   /id="PRO_0000223105"
FT   ZN_FING         246..283
FT                   /note="SWIM-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00325"
FT   REGION          1..46
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          133..161
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         763
FT                   /note="S -> R"
FT                   /evidence="ECO:0000269|PubMed:26566883"
FT                   /id="VAR_076431"
FT   VARIANT         913..1215
FT                   /note="Missing (in NEDMAGA)"
FT                   /evidence="ECO:0000269|PubMed:29198722"
FT                   /id="VAR_080756"
FT   VARIANT         1163
FT                   /note="R -> W (in AFND; dbSNP:rs587777695)"
FT                   /evidence="ECO:0000269|PubMed:25105228"
FT                   /id="VAR_071802"
SQ   SEQUENCE   1215 AA;  133470 MW;  828B5AA0644EECE0 CRC64;
     MAERGQQPPP AKRLCCRPGG GGGGGGSSGG GGGAGGGYSS ACRPGPRAGG AAAAAACGGG
     AALGLLPPGK TQSPESLLDI AARRVAEKWP FQRVEERFER IPEPVQRRIV YWSFPRSERE
     ICMYSSFNTG GGAAGGPGDD SGGGGGAGGG GGGGSSSSPA ATSAAATSAA AAAAAAAAAA
     AAAAGAGAPS VGAAGAADGG DETRLPFRRG IALLESGCVD NVLQVGFHLS GTVTEPAIQS
     EPETVCNVAI SFDRCKITSV TCSCGNKDIF YCAHVVALSL YRIRKPDQVK LHLPISETLF
     QMNRDQLQKF VQYLITVHHT EVLPTAQKLA DEILSQNSEI NQVHGAPDPT AGASIDDENC
     WHLDEEQVQE QVKLFLSQGG YHGSGKQLNL LFAKVREMLK MRDSNGARML TLITEQFMAD
     PRLSLWRQQG TAMTDKYRQL WDELGALWMC IVLNPHCKLE QKASWLKQLK KWNSVDVCPW
     EDGNHGSELP NLTNALPQGA NANQDSSNRP HRTVFTRAIE ACDLHWQDSH LQHIISSDLY
     TNYCYHDDTE NSLFDSRGWP LWHEHVPTAC ARVDALRSHG YPREALRLAI AIVNTLRRQQ
     QKQLEMFRTQ KKELPHKNIT SITNLEGWVG HPLDPVGTLF SSLMEACRID DENLSGFSDF
     TENMGQCKSL EYQHLPAHKF LEEGESYLTL AVEVALIGLG QQRIMPDGLY TQEKVCRNEE
     QLISKLQEIE LDDTLVKIFR KQAVFLLEAG PYSGLGEIIH RESVPMHTFA KYLFTSLLPH
     DAELAYKIAL RAMRLLVLES TAPSGDLTRP HHIASVVPNR YPRWFTLSHI ESQQCELAST
     MLTAAKGDVR RLETVLESIQ KNIHSSSHIF KLAQDAFKIA TLMDSLPDIT LLKVSLELGL
     QVMRMTLSTL NWRRREMVRW LVTCATEVGV YALDSIMQTW FTLFTPTEAT SIVATTVMSN
     STIVRLHLDC HQQEKLASSA RTLALQCAMK DPQNCALSAL TLCEKDHIAF ETAYQIVLDA
     ATTGMSYTQL FTIARYMEHR GYPMRAYKLA TLAMTHLNLS YNQDTHPAIN DVLWACALSH
     SLGKNELAAI IPLVVKSVKC ATVLSDILRR CTLTTPGMVG LHGRRNSGKL MSLDKAPLRQ
     LLDATIGAYI NTTHSRLTHI SPRHYSEFIE FLSKARETFL MAHDGHIQFT QFIDNLKQIY
     KGKKKLMMLV RERFG
//