Full text data of ANKS6
ANKS6
(ANKRD14, PKDR1, SAMD6)
[Confidence: low (only semi-automatic identification from reviews)]
Ankyrin repeat and SAM domain-containing protein 6 (Ankyrin repeat domain-containing protein 14; SamCystin; Sterile alpha motif domain-containing protein 6; SAM domain-containing protein 6)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ankyrin repeat and SAM domain-containing protein 6 (Ankyrin repeat domain-containing protein 14; SamCystin; Sterile alpha motif domain-containing protein 6; SAM domain-containing protein 6)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q68DC2
ID ANKS6_HUMAN Reviewed; 871 AA.
AC Q68DC2; A0SE62; Q5VSL0; Q5VSL2; Q5VSL3; Q5VSL4; Q68DB8; Q6P2R2;
read moreAC Q8N9L6; Q96D62;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 2.
DT 22-JAN-2014, entry version 92.
DE RecName: Full=Ankyrin repeat and SAM domain-containing protein 6;
DE AltName: Full=Ankyrin repeat domain-containing protein 14;
DE AltName: Full=SamCystin;
DE AltName: Full=Sterile alpha motif domain-containing protein 6;
DE Short=SAM domain-containing protein 6;
GN Name=ANKS6; Synonyms=ANKRD14, PKDR1, SAMD6;
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].
RX PubMed=16207829; DOI=10.1681/ASN.2005060601;
RA Brown J.H., Bihoreau M.-T., Hoffmann S., Kranzlin B., Tychinskaya I.,
RA Obermuller N., Podlich D., Boehn S.N., Kaisaki P.J., Megel N.,
RA Danoy P., Copley R.R., Broxholme J., Witzgall R., Lathrop M.,
RA Gretz N., Gauguier D.;
RT "Missense mutation in sterile alpha motif of novel protein SamCystin
RT is associated with polycystic kidney disease in (cy/+) rat.";
RL J. Am. Soc. Nephrol. 16:3517-3526(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 94-871 (ISOFORM 1), AND
RP VARIANT ILE-644.
RC TISSUE=Fetal kidney, and Uterus;
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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 322-871 (ISOFORM 1), AND
RP VARIANT ILE-644.
RC TISSUE=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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 533-871 (ISOFORM 3), AND
RP VARIANT ILE-644.
RC TISSUE=Cerebellum;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP VARIANTS TRP-222; GLN-440; SER-640; ILE-644 AND ALA-735.
RX PubMed=18434273; DOI=10.1016/j.ejmg.2008.02.007;
RA Kaisaki P.J., Bergmann C., Brown J.H., Outeda P., Lens X.M.,
RA Peters D.J., Gretz N., Gauguier D., Bihoreau M.T.;
RT "Genomic organization and mutation screening of the human ortholog of
RT Pkdr1 associated with polycystic kidney disease in the rat.";
RL Eur. J. Med. Genet. 51:325-331(2008).
RN [10]
RP VARIANTS NPHP16 PRO-312 AND GLN441ARG, FUNCTION, INTERACTION WITH
RP INVS; NEK8 AND NPHP3, AND DOMAIN.
RX PubMed=23793029; DOI=10.1038/ng.2681;
RA Hoff S., Halbritter J., Epting D., Frank V., Nguyen T.M.,
RA van Reeuwijk J., Boehlke C., Schell C., Yasunaga T., Helmstadter M.,
RA Mergen M., Filhol E., Boldt K., Horn N., Ueffing M., Otto E.A.,
RA Eisenberger T., Elting M.W., van Wijk J.A., Bockenhauer D.,
RA Sebire N.J., Rittig S., Vyberg M., Ring T., Pohl M., Pape L.,
RA Neuhaus T.J., Elshakhs N.A., Koon S.J., Harris P.C., Grahammer F.,
RA Huber T.B., Kuehn E.W., Kramer-Zucker A., Bolz H.J., Roepman R.,
RA Saunier S., Walz G., Hildebrandt F., Bergmann C., Lienkamp S.S.;
RT "ANKS6 is a central component of a nephronophthisis module linking
RT NEK8 to INVS and NPHP3.";
RL Nat. Genet. 45:951-956(2013).
CC -!- FUNCTION: Required for renal function.
CC -!- SUBUNIT: Self-associates. Interacts (via SAM domain) with BICC1
CC (via KH domains) in an RNA-dependent manner (By similarity).
CC Central component of a complex containing at least ANKS6, INVS,
CC NEK8 and NPHP3. ANKS6 may organize complex assembly by linking
CC INVS and NPHP3 to NEK8 and INVS may target the complex to the
CC proximal ciliary axoneme.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium (By similarity).
CC Cytoplasm (By similarity). Note=Localizes to the proximal region
CC of the primary cilium in the presence of INVS (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q68DC2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q68DC2-3; Sequence=VSP_016496, VSP_016497;
CC Note=Gene prediction confirmed by EST data;
CC Name=3;
CC IsoId=Q68DC2-4; Sequence=VSP_016498;
CC Note=No experimental confirmation available;
CC -!- DOMAIN: The ankyrin repeats and the SAM domain are essential for
CC self-association (By similarity). Ankyrin repeats are necessary
CC and sufficient for NEK8-binding.
CC -!- PTM: Hydroxylated at Asn-138, most probably by HIF1AN. This
CC hydroxylation results in decreased NEK8-binding.
CC -!- DISEASE: Nephronophthisis 16 (NPHP16) [MIM:615382]: A form of
CC nephronophthisis, a chronic tubulo-interstitial nephritis that
CC progresses to end-stage renal failure. Some patients have cystic
CC kidneys of normal size and no extrarenal manifestations, whereas
CC others have enlarged renal size and severe extrarenal defects,
CC including hypertrophic obstructive cardiomyopathy, aortic
CC stenosis, pulmonary stenosis, patent ductus arteriosus, situs
CC inversus, and periportal liver fibrosis. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Contains 11 ANK repeats.
CC -!- SIMILARITY: Contains 1 SAM (sterile alpha motif) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH64367.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAC04317.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAH18298.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAH69985.2; Type=Erroneous gene model prediction;
CC Sequence=CAH69986.2; Type=Erroneous gene model prediction;
CC Sequence=CAH71295.2; Type=Erroneous gene model prediction;
CC Sequence=CAH71296.2; Type=Erroneous gene model prediction;
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DR EMBL; DQ309791; ABC48694.1; -; Genomic_DNA.
DR EMBL; DQ309777; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309778; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309779; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309780; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309781; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309782; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309783; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309784; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309785; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309786; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309787; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309788; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309789; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309790; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; AL353782; CAH71295.2; ALT_SEQ; Genomic_DNA.
DR EMBL; AL807776; CAH71295.2; JOINED; Genomic_DNA.
DR EMBL; AL353782; CAH71296.2; ALT_SEQ; Genomic_DNA.
DR EMBL; AL807776; CAH71296.2; JOINED; Genomic_DNA.
DR EMBL; AL353782; CAM14169.1; -; Genomic_DNA.
DR EMBL; AL807776; CAM14169.1; JOINED; Genomic_DNA.
DR EMBL; AL807776; CAH69985.2; ALT_SEQ; Genomic_DNA.
DR EMBL; AL353782; CAH69985.2; JOINED; Genomic_DNA.
DR EMBL; AL807776; CAH69986.2; ALT_SEQ; Genomic_DNA.
DR EMBL; AL353782; CAH69986.2; JOINED; Genomic_DNA.
DR EMBL; AL807776; CAM13062.1; -; Genomic_DNA.
DR EMBL; AL353782; CAM13062.1; JOINED; Genomic_DNA.
DR EMBL; CR749467; CAH18298.1; ALT_INIT; mRNA.
DR EMBL; CR749472; CAH18302.1; -; mRNA.
DR EMBL; BC064367; AAH64367.1; ALT_INIT; mRNA.
DR EMBL; AK094247; BAC04317.1; ALT_INIT; mRNA.
DR RefSeq; NP_775822.3; NM_173551.3.
DR RefSeq; XP_005251852.1; XM_005251795.1.
DR UniGene; Hs.406890; -.
DR ProteinModelPortal; Q68DC2; -.
DR SMR; Q68DC2; 11-414.
DR IntAct; Q68DC2; 1.
DR MINT; MINT-8201748; -.
DR PhosphoSite; Q68DC2; -.
DR DMDM; 83305683; -.
DR PaxDb; Q68DC2; -.
DR PRIDE; Q68DC2; -.
DR DNASU; 203286; -.
DR Ensembl; ENST00000353234; ENSP00000297837; ENSG00000165138.
DR Ensembl; ENST00000375018; ENSP00000364158; ENSG00000165138.
DR GeneID; 203286; -.
DR KEGG; hsa:203286; -.
DR UCSC; uc004ayt.3; human.
DR CTD; 203286; -.
DR GeneCards; GC09M101493; -.
DR H-InvDB; HIX0025696; -.
DR HGNC; HGNC:26724; ANKS6.
DR HPA; HPA008355; -.
DR MIM; 615370; gene.
DR MIM; 615382; phenotype.
DR neXtProt; NX_Q68DC2; -.
DR Orphanet; 93591; Infantile autosomal recessive medullary cystic kidney disease.
DR Orphanet; 93592; Juvenile autosomal recessive medullary cystic kidney disease.
DR PharmGKB; PA134931829; -.
DR eggNOG; COG0666; -.
DR HOVERGEN; HBG059049; -.
DR OMA; DRKHRDL; -.
DR OrthoDB; EOG7DRJ2G; -.
DR GenomeRNAi; 203286; -.
DR NextBio; 90399; -.
DR PRO; PR:Q68DC2; -.
DR ArrayExpress; Q68DC2; -.
DR Bgee; Q68DC2; -.
DR CleanEx; HS_ANKS6; -.
DR Genevestigator; Q68DC2; -.
DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 1.25.40.20; -; 3.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR020683; Ankyrin_rpt-contain_dom.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed.
DR InterPro; IPR021129; SAM_type1.
DR Pfam; PF12796; Ank_2; 3.
DR Pfam; PF00536; SAM_1; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 9.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF48403; SSF48403; 3.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 7.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Cell projection; Ciliopathy; Cilium;
KW Complete proteome; Cytoplasm; Disease mutation; Hydroxylation;
KW Joubert syndrome; Nephronophthisis; Polymorphism; Reference proteome;
KW Repeat.
FT CHAIN 1 871 Ankyrin repeat and SAM domain-containing
FT protein 6.
FT /FTId=PRO_0000067065.
FT REPEAT 8 37 ANK 1.
FT REPEAT 77 106 ANK 2.
FT REPEAT 110 139 ANK 3.
FT REPEAT 143 172 ANK 4.
FT REPEAT 190 219 ANK 5.
FT REPEAT 224 253 ANK 6.
FT REPEAT 257 289 ANK 7.
FT REPEAT 291 321 ANK 8.
FT REPEAT 325 354 ANK 9.
FT REPEAT 359 388 ANK 10.
FT REPEAT 392 423 ANK 11.
FT DOMAIN 773 836 SAM.
FT COMPBIAS 617 769 Ser-rich.
FT MOD_RES 138 138 3-hydroxyasparagine (By similarity).
FT VAR_SEQ 288 335 DEEKRRPDIFHALKMGNFQLVKEIADEDPSHVNLVNGDGAT
FT PLMLAAV -> GQAACPPWLHRGPQIVFMWLKLRIALLEGH
FT AELRVQPCRPLRLRKWCA (in isoform 2).
FT /FTId=VSP_016496.
FT VAR_SEQ 336 871 Missing (in isoform 2).
FT /FTId=VSP_016497.
FT VAR_SEQ 714 714 K -> KQ (in isoform 3).
FT /FTId=VSP_016498.
FT VARIANT 222 222 R -> W (in dbSNP:rs41283630).
FT /FTId=VAR_070105.
FT VARIANT 312 312 A -> P (in NPHP16).
FT /FTId=VAR_070106.
FT VARIANT 440 440 R -> Q.
FT /FTId=VAR_070107.
FT VARIANT 441 441 Q -> R (in NPHP16; dbSNP:rs377750405).
FT /FTId=VAR_070108.
FT VARIANT 640 640 G -> S.
FT /FTId=VAR_070109.
FT VARIANT 644 644 V -> I (in dbSNP:rs6415847).
FT /FTId=VAR_034794.
FT VARIANT 735 735 P -> A (in dbSNP:rs79414550).
FT /FTId=VAR_070110.
FT CONFLICT 244 244 L -> P (in Ref. 3; CAH18298).
FT CONFLICT 402 402 L -> P (in Ref. 4; CAH18302).
FT CONFLICT 647 647 S -> G (in Ref. 5; BAC04317).
FT CONFLICT 808 808 T -> A (in Ref. 4; CAH18302).
SQ SEQUENCE 871 AA; 92219 MW; C4E3AFFE9C9DD6C8 CRC64;
MGEGGLPPAF QLLLRACDQG DTETARRLLE PGAAEPAERG AEPEAGAEPA GAEVAGPGAA
AAGAVGAPVP VDCSDEAGNT ALQFAAAGGH EPLVRFLLRR GASVNSRNHY GWSALMQAAR
FGHVSVAHLL LDHGADVNAQ NRLGASVLTV ASRGGHLGVV KLLLEAGAFV DHHHPSGEQL
GLGGSRDEPL DITALMAAIQ HGHEAVVRLL MEWGADPNHA ARTVGWSPLM LAALTGRLGV
AQQLVEKGAN PDHLSVLEKT AFEVALDCKH RDLVDYLDPL TTVRPKTDEE KRRPDIFHAL
KMGNFQLVKE IADEDPSHVN LVNGDGATPL MLAAVTGQLA LVQLLVERHA DVDKQDSVHG
WTALMQATYH GNKEIVKYLL NQGADVTLRA KNGYTAFDLV MLLNDPDTEL VRLLASVCMQ
VNKDKGRPSH QPPLPHSKVR QPWSIPVLPD DKGGLKSWWN RMSNRFRKLK LMQTLPRGLS
SNQPLPFSDE PEPALDSTMR AAPQDKTSRS ALPDAAPVTK DNGPGSTRGE KEDTLLTTML
RNGAPLTRLP SDKLKAVIPP FLPPSSFELW SSDRSRTRHN GKADPMKTAL PQRASRGHPV
GGGGTDTTPV RPVKFPSLPR SPASSANSGN FNHSPHSSGG SSGVGVSRHG GELLNRSGGS
IDNVLSQIAA QRKKAAGLLE QKPSHRSSPV GPAPGSSPSE LPASPAGGSA PVGKKLETSK
RPPSGTSTTS KSTSPTLTPS PSPKGHTAES SVSSSSSHRQ SKSSGGSSSG TITDEDELTG
ILKKLSLEKY QPIFEEQEVD MEAFLTLTDG DLKELGIKTD GSRQQILAAI SELNAGKGRE
RQILQETIHN FHSSFESSAS NTRAPGNSPC A
//
ID ANKS6_HUMAN Reviewed; 871 AA.
AC Q68DC2; A0SE62; Q5VSL0; Q5VSL2; Q5VSL3; Q5VSL4; Q68DB8; Q6P2R2;
read moreAC Q8N9L6; Q96D62;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 2.
DT 22-JAN-2014, entry version 92.
DE RecName: Full=Ankyrin repeat and SAM domain-containing protein 6;
DE AltName: Full=Ankyrin repeat domain-containing protein 14;
DE AltName: Full=SamCystin;
DE AltName: Full=Sterile alpha motif domain-containing protein 6;
DE Short=SAM domain-containing protein 6;
GN Name=ANKS6; Synonyms=ANKRD14, PKDR1, SAMD6;
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].
RX PubMed=16207829; DOI=10.1681/ASN.2005060601;
RA Brown J.H., Bihoreau M.-T., Hoffmann S., Kranzlin B., Tychinskaya I.,
RA Obermuller N., Podlich D., Boehn S.N., Kaisaki P.J., Megel N.,
RA Danoy P., Copley R.R., Broxholme J., Witzgall R., Lathrop M.,
RA Gretz N., Gauguier D.;
RT "Missense mutation in sterile alpha motif of novel protein SamCystin
RT is associated with polycystic kidney disease in (cy/+) rat.";
RL J. Am. Soc. Nephrol. 16:3517-3526(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 94-871 (ISOFORM 1), AND
RP VARIANT ILE-644.
RC TISSUE=Fetal kidney, and Uterus;
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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 322-871 (ISOFORM 1), AND
RP VARIANT ILE-644.
RC TISSUE=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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 533-871 (ISOFORM 3), AND
RP VARIANT ILE-644.
RC TISSUE=Cerebellum;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP VARIANTS TRP-222; GLN-440; SER-640; ILE-644 AND ALA-735.
RX PubMed=18434273; DOI=10.1016/j.ejmg.2008.02.007;
RA Kaisaki P.J., Bergmann C., Brown J.H., Outeda P., Lens X.M.,
RA Peters D.J., Gretz N., Gauguier D., Bihoreau M.T.;
RT "Genomic organization and mutation screening of the human ortholog of
RT Pkdr1 associated with polycystic kidney disease in the rat.";
RL Eur. J. Med. Genet. 51:325-331(2008).
RN [10]
RP VARIANTS NPHP16 PRO-312 AND GLN441ARG, FUNCTION, INTERACTION WITH
RP INVS; NEK8 AND NPHP3, AND DOMAIN.
RX PubMed=23793029; DOI=10.1038/ng.2681;
RA Hoff S., Halbritter J., Epting D., Frank V., Nguyen T.M.,
RA van Reeuwijk J., Boehlke C., Schell C., Yasunaga T., Helmstadter M.,
RA Mergen M., Filhol E., Boldt K., Horn N., Ueffing M., Otto E.A.,
RA Eisenberger T., Elting M.W., van Wijk J.A., Bockenhauer D.,
RA Sebire N.J., Rittig S., Vyberg M., Ring T., Pohl M., Pape L.,
RA Neuhaus T.J., Elshakhs N.A., Koon S.J., Harris P.C., Grahammer F.,
RA Huber T.B., Kuehn E.W., Kramer-Zucker A., Bolz H.J., Roepman R.,
RA Saunier S., Walz G., Hildebrandt F., Bergmann C., Lienkamp S.S.;
RT "ANKS6 is a central component of a nephronophthisis module linking
RT NEK8 to INVS and NPHP3.";
RL Nat. Genet. 45:951-956(2013).
CC -!- FUNCTION: Required for renal function.
CC -!- SUBUNIT: Self-associates. Interacts (via SAM domain) with BICC1
CC (via KH domains) in an RNA-dependent manner (By similarity).
CC Central component of a complex containing at least ANKS6, INVS,
CC NEK8 and NPHP3. ANKS6 may organize complex assembly by linking
CC INVS and NPHP3 to NEK8 and INVS may target the complex to the
CC proximal ciliary axoneme.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium (By similarity).
CC Cytoplasm (By similarity). Note=Localizes to the proximal region
CC of the primary cilium in the presence of INVS (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q68DC2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q68DC2-3; Sequence=VSP_016496, VSP_016497;
CC Note=Gene prediction confirmed by EST data;
CC Name=3;
CC IsoId=Q68DC2-4; Sequence=VSP_016498;
CC Note=No experimental confirmation available;
CC -!- DOMAIN: The ankyrin repeats and the SAM domain are essential for
CC self-association (By similarity). Ankyrin repeats are necessary
CC and sufficient for NEK8-binding.
CC -!- PTM: Hydroxylated at Asn-138, most probably by HIF1AN. This
CC hydroxylation results in decreased NEK8-binding.
CC -!- DISEASE: Nephronophthisis 16 (NPHP16) [MIM:615382]: A form of
CC nephronophthisis, a chronic tubulo-interstitial nephritis that
CC progresses to end-stage renal failure. Some patients have cystic
CC kidneys of normal size and no extrarenal manifestations, whereas
CC others have enlarged renal size and severe extrarenal defects,
CC including hypertrophic obstructive cardiomyopathy, aortic
CC stenosis, pulmonary stenosis, patent ductus arteriosus, situs
CC inversus, and periportal liver fibrosis. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Contains 11 ANK repeats.
CC -!- SIMILARITY: Contains 1 SAM (sterile alpha motif) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH64367.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAC04317.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAH18298.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAH69985.2; Type=Erroneous gene model prediction;
CC Sequence=CAH69986.2; Type=Erroneous gene model prediction;
CC Sequence=CAH71295.2; Type=Erroneous gene model prediction;
CC Sequence=CAH71296.2; Type=Erroneous gene model prediction;
CC -----------------------------------------------------------------------
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DR EMBL; DQ309791; ABC48694.1; -; Genomic_DNA.
DR EMBL; DQ309777; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309778; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309779; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309780; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309781; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309782; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309783; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309784; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309785; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309786; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309787; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309788; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309789; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; DQ309790; ABC48694.1; JOINED; Genomic_DNA.
DR EMBL; AL353782; CAH71295.2; ALT_SEQ; Genomic_DNA.
DR EMBL; AL807776; CAH71295.2; JOINED; Genomic_DNA.
DR EMBL; AL353782; CAH71296.2; ALT_SEQ; Genomic_DNA.
DR EMBL; AL807776; CAH71296.2; JOINED; Genomic_DNA.
DR EMBL; AL353782; CAM14169.1; -; Genomic_DNA.
DR EMBL; AL807776; CAM14169.1; JOINED; Genomic_DNA.
DR EMBL; AL807776; CAH69985.2; ALT_SEQ; Genomic_DNA.
DR EMBL; AL353782; CAH69985.2; JOINED; Genomic_DNA.
DR EMBL; AL807776; CAH69986.2; ALT_SEQ; Genomic_DNA.
DR EMBL; AL353782; CAH69986.2; JOINED; Genomic_DNA.
DR EMBL; AL807776; CAM13062.1; -; Genomic_DNA.
DR EMBL; AL353782; CAM13062.1; JOINED; Genomic_DNA.
DR EMBL; CR749467; CAH18298.1; ALT_INIT; mRNA.
DR EMBL; CR749472; CAH18302.1; -; mRNA.
DR EMBL; BC064367; AAH64367.1; ALT_INIT; mRNA.
DR EMBL; AK094247; BAC04317.1; ALT_INIT; mRNA.
DR RefSeq; NP_775822.3; NM_173551.3.
DR RefSeq; XP_005251852.1; XM_005251795.1.
DR UniGene; Hs.406890; -.
DR ProteinModelPortal; Q68DC2; -.
DR SMR; Q68DC2; 11-414.
DR IntAct; Q68DC2; 1.
DR MINT; MINT-8201748; -.
DR PhosphoSite; Q68DC2; -.
DR DMDM; 83305683; -.
DR PaxDb; Q68DC2; -.
DR PRIDE; Q68DC2; -.
DR DNASU; 203286; -.
DR Ensembl; ENST00000353234; ENSP00000297837; ENSG00000165138.
DR Ensembl; ENST00000375018; ENSP00000364158; ENSG00000165138.
DR GeneID; 203286; -.
DR KEGG; hsa:203286; -.
DR UCSC; uc004ayt.3; human.
DR CTD; 203286; -.
DR GeneCards; GC09M101493; -.
DR H-InvDB; HIX0025696; -.
DR HGNC; HGNC:26724; ANKS6.
DR HPA; HPA008355; -.
DR MIM; 615370; gene.
DR MIM; 615382; phenotype.
DR neXtProt; NX_Q68DC2; -.
DR Orphanet; 93591; Infantile autosomal recessive medullary cystic kidney disease.
DR Orphanet; 93592; Juvenile autosomal recessive medullary cystic kidney disease.
DR PharmGKB; PA134931829; -.
DR eggNOG; COG0666; -.
DR HOVERGEN; HBG059049; -.
DR OMA; DRKHRDL; -.
DR OrthoDB; EOG7DRJ2G; -.
DR GenomeRNAi; 203286; -.
DR NextBio; 90399; -.
DR PRO; PR:Q68DC2; -.
DR ArrayExpress; Q68DC2; -.
DR Bgee; Q68DC2; -.
DR CleanEx; HS_ANKS6; -.
DR Genevestigator; Q68DC2; -.
DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 1.25.40.20; -; 3.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR020683; Ankyrin_rpt-contain_dom.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed.
DR InterPro; IPR021129; SAM_type1.
DR Pfam; PF12796; Ank_2; 3.
DR Pfam; PF00536; SAM_1; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 9.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF48403; SSF48403; 3.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 7.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Cell projection; Ciliopathy; Cilium;
KW Complete proteome; Cytoplasm; Disease mutation; Hydroxylation;
KW Joubert syndrome; Nephronophthisis; Polymorphism; Reference proteome;
KW Repeat.
FT CHAIN 1 871 Ankyrin repeat and SAM domain-containing
FT protein 6.
FT /FTId=PRO_0000067065.
FT REPEAT 8 37 ANK 1.
FT REPEAT 77 106 ANK 2.
FT REPEAT 110 139 ANK 3.
FT REPEAT 143 172 ANK 4.
FT REPEAT 190 219 ANK 5.
FT REPEAT 224 253 ANK 6.
FT REPEAT 257 289 ANK 7.
FT REPEAT 291 321 ANK 8.
FT REPEAT 325 354 ANK 9.
FT REPEAT 359 388 ANK 10.
FT REPEAT 392 423 ANK 11.
FT DOMAIN 773 836 SAM.
FT COMPBIAS 617 769 Ser-rich.
FT MOD_RES 138 138 3-hydroxyasparagine (By similarity).
FT VAR_SEQ 288 335 DEEKRRPDIFHALKMGNFQLVKEIADEDPSHVNLVNGDGAT
FT PLMLAAV -> GQAACPPWLHRGPQIVFMWLKLRIALLEGH
FT AELRVQPCRPLRLRKWCA (in isoform 2).
FT /FTId=VSP_016496.
FT VAR_SEQ 336 871 Missing (in isoform 2).
FT /FTId=VSP_016497.
FT VAR_SEQ 714 714 K -> KQ (in isoform 3).
FT /FTId=VSP_016498.
FT VARIANT 222 222 R -> W (in dbSNP:rs41283630).
FT /FTId=VAR_070105.
FT VARIANT 312 312 A -> P (in NPHP16).
FT /FTId=VAR_070106.
FT VARIANT 440 440 R -> Q.
FT /FTId=VAR_070107.
FT VARIANT 441 441 Q -> R (in NPHP16; dbSNP:rs377750405).
FT /FTId=VAR_070108.
FT VARIANT 640 640 G -> S.
FT /FTId=VAR_070109.
FT VARIANT 644 644 V -> I (in dbSNP:rs6415847).
FT /FTId=VAR_034794.
FT VARIANT 735 735 P -> A (in dbSNP:rs79414550).
FT /FTId=VAR_070110.
FT CONFLICT 244 244 L -> P (in Ref. 3; CAH18298).
FT CONFLICT 402 402 L -> P (in Ref. 4; CAH18302).
FT CONFLICT 647 647 S -> G (in Ref. 5; BAC04317).
FT CONFLICT 808 808 T -> A (in Ref. 4; CAH18302).
SQ SEQUENCE 871 AA; 92219 MW; C4E3AFFE9C9DD6C8 CRC64;
MGEGGLPPAF QLLLRACDQG DTETARRLLE PGAAEPAERG AEPEAGAEPA GAEVAGPGAA
AAGAVGAPVP VDCSDEAGNT ALQFAAAGGH EPLVRFLLRR GASVNSRNHY GWSALMQAAR
FGHVSVAHLL LDHGADVNAQ NRLGASVLTV ASRGGHLGVV KLLLEAGAFV DHHHPSGEQL
GLGGSRDEPL DITALMAAIQ HGHEAVVRLL MEWGADPNHA ARTVGWSPLM LAALTGRLGV
AQQLVEKGAN PDHLSVLEKT AFEVALDCKH RDLVDYLDPL TTVRPKTDEE KRRPDIFHAL
KMGNFQLVKE IADEDPSHVN LVNGDGATPL MLAAVTGQLA LVQLLVERHA DVDKQDSVHG
WTALMQATYH GNKEIVKYLL NQGADVTLRA KNGYTAFDLV MLLNDPDTEL VRLLASVCMQ
VNKDKGRPSH QPPLPHSKVR QPWSIPVLPD DKGGLKSWWN RMSNRFRKLK LMQTLPRGLS
SNQPLPFSDE PEPALDSTMR AAPQDKTSRS ALPDAAPVTK DNGPGSTRGE KEDTLLTTML
RNGAPLTRLP SDKLKAVIPP FLPPSSFELW SSDRSRTRHN GKADPMKTAL PQRASRGHPV
GGGGTDTTPV RPVKFPSLPR SPASSANSGN FNHSPHSSGG SSGVGVSRHG GELLNRSGGS
IDNVLSQIAA QRKKAAGLLE QKPSHRSSPV GPAPGSSPSE LPASPAGGSA PVGKKLETSK
RPPSGTSTTS KSTSPTLTPS PSPKGHTAES SVSSSSSHRQ SKSSGGSSSG TITDEDELTG
ILKKLSLEKY QPIFEEQEVD MEAFLTLTDG DLKELGIKTD GSRQQILAAI SELNAGKGRE
RQILQETIHN FHSSFESSAS NTRAPGNSPC A
//
MIM
615370
*RECORD*
*FIELD* NO
615370
*FIELD* TI
*615370 ANKYRIN REPEAT AND STERILE ALPHA MOTIF DOMAINS-CONTAINING PROTEIN
6; ANKS6
read more;;PKDR1;;
SAMCYSTIN
*FIELD* TX
DESCRIPTION
ANKS6 assembles a complex of ciliary proteins required for renal and
cardiovascular development (Hoff et al., 2013).
CLONING
By searching an EST database for sequences similar to rat Pkdr1, Kaisaki
et al. (2008) identified human ANKS6, which they called PKDR1. The
deduced protein contains an N-terminal ankyrin (see 612641) repeat
domain and a C-terminal sterile alpha motif (SAM) domain. Database
analysis revealed 4 possible ANKS6 isoforms.
Hoff et al. (2013) stated that the N-terminal half the deduced 871-amino
acid human ANKS6 protein contains 9 ankyrin repeats. Immunohistochemical
analysis revealed that Anks6 localized to the proximal segment of the
cilium in mouse IMCD3 innermedullary collecting duct cells.
GENE FUNCTION
Using mass spectrometry and coimmunoprecipitation analysis, Hoff et al.
(2013) found that the ciliary proteins ANKS6, NPHP3 (608002), INVS
(243305), and NEK8 (609799) interacted in a complex. The kinase domain
and a central region of NEK8 were required for interaction with human
NPHP3 and INVS and with rat Anks6. Interaction of NEK8 with NPHP3 was
enhanced by coexpression of rat Anks6. ANKS6 also interacted with HIF1AN
(606615), an oxygen sensor that hydroxylates HIF1-alpha (HIF1A; 603348)
and other ankyrin repeat proteins under normoxic conditions.
Coimmunoprecipitation experiments showed that HIF1AN facilitated
formation of a complex containing rat Anks6 and human NPHP3 and INVS.
Association of rat Anks6 with human NEK8 required hydroxylation of
Anks6. Hoff et al. (2013) concluded that oxygen-dependent hydroxylation
of ANKS6 by HIF1AN regulates the composition of the ANKS6-containing
ciliary complex.
GENE STRUCTURE
Kaisaki et al. (2008) determined that the ANKS6 gene contains 15 coding
exons and spans 64.5 kb.
MAPPING
By genomic sequence analysis, Kaisaki et al. (2008) mapped the ANKS6
gene to chromosome 9q22.33.
MOLECULAR GENETICS
In affected members of 6 unrelated families with nephronophthisis-16
(NPHP16; 615382), Hoff et al. (2013) identified 6 different homozygous
mutations in the ANKS6 gene (see, e.g., 615370.0001-615370.0005). There
were 2 truncating mutations, 2 splice site mutations, and 2 missense
mutations. ANKS6 was chosen for study based on findings in animal models
and on its interactive role of with other cilia-related proteins.
Affected individuals in 5 families had infantile onset of progressive
polycystic kidney disease leading to renal failure, whereas those in 1
family had juvenile onset of the disorder. Patients with missense
mutations showed nonenlarged cystic kidneys and no extrarenal
manifestations, whereas those with splice site and truncating mutations
had enlarged renal size and severe extrarenal defects, including
hypertrophic obstructive cardiomyopathy, aortic stenosis, pulmonary
stenosis, patent ductus arteriosus, situs inversus, and periportal liver
fibrosis. The findings indicated that ANKS6 has a role in renal and
cardiovascular development.
ANIMAL MODEL
Kaisaki et al. (2008) reported that a mutation in the SAM domain of rat
Pkdr1 causes polycystic kidney disease (see 173900).
Using antisense morpholinos, Hoff et al. (2013) found that depletion of
Anks6, Nphp3, or Nek8 in zebrafish resulted in a similar phenotype
characterized by formation of pronephric cysts and a defect in early
heart looping. In Xenopus, knockdown of Anks6, Nphp3, or Invs caused
gross body edema typical of a renal excretory defect. Knockdown of
Xenopus Anks6 or Nek8 resulted in notable simplification of proximal
pronephros convolute. Coexpression of Anks6 mRNA partially rescued
defects mediated by Nek8 knockdown, suggesting overlapping roles for
Nek8 and Anks6 during early tubular morphogenesis.
*FIELD* AV
.0001
NEPHRONOPHTHISIS 16
ANKS6, GLN441ARG
In a Serbian patient with nephronophthisis-16 (NPHP16; 615382), Hoff et
al. (2013) identified a homozygous c.1322A-G transition in exon 6 of the
ANKS6 gene, resulting in a gln441-to-arg (Q441R) substitution at a
highly conserved residue. The unaffected parents were heterozygous for
the mutation. The patient had polycystic kidney disease resulting in
chronic renal failure in early childhood, but did not have heart or
liver abnormalities. Although the Q441R mutation did not alter the
interaction of ANKS6 with other NPHP proteins or its ciliary
localization, the mutant protein was unable to rescue the renal
phenotype in Xenopus knockdown embryos, supporting its pathogenicity.
.0002
NEPHRONOPHTHISIS 16
ANKS6, IVS10AS, C-G, -3
In a patient, born of consanguineous Iranian parents, with NPHP16
(615382), Hoff et al. (2013) identified a homozygous C-to-G transition
in intron 10 of the ANKS6 gene (c.1973-3C-G), predicted to result in a
splice site mutation. The unaffected parents were heterozygous for the
mutation. The patient had polycystic kidney disease resulting in
end-stage renal disease by age 2 years and renal transplantation at age
4. The patient also had aortic and pulmonic stenosis and periportal
liver fibrosis.
.0003
NEPHRONOPHTHISIS 16
ANKS6, 11-BP DEL, NT2054
In a Danish patient with NPHP16 (615382), Hoff et al. (2013) identified
a homozygous 11-bp deletion (c.2054_2064del) in exon 11 of the ANKS6
gene, resulting in a frameshift and premature termination
(His685ProfsTer12). The unaffected parents were heterozygous for the
mutation. The patient had polycystic kidney disease resulting in
end-stage renal disease at age 1 year, aortic stenosis, periportal liver
fibrosis, and delayed psychomotor development.
.0004
NEPHRONOPHTHISIS 16
ANKS6, 3-BP DEL, 2370TCA
In an Indian patient with NPHP16 (615382), Hoff et al. (2013) identified
a homozygous 3-bp deletion (c.2370_2372delTCA) in exon 13 of the ANKS6
gene, resulting in a tyr790-to-ter (Y790X) substitution. The unaffected
parents were heterozygous for the mutation. The patient had polycystic
kidney disease resulting in end-stage renal disease at birth, aortic
stenosis, hypertrophic cardiomyopathy, patent ductus arteriosus,
cholestatic hepatopathy, and situs inversus. The infant died at age 4
months. A presumably affected sib died in utero with polycystic kidney
disease and oligohydramnios.
.0005
NEPHRONOPHTHISIS 16
ANKS6, IVS14AS, A-C, -2
In affected members of a consanguineous Turkish family with NPHP16
(615382), Hoff et al. (2013) identified a homozygous A-to-C transversion
at the acceptor splice site of intron 14 of the ANKS6 gene
(c.2512-2A-C). Each parent was heterozygous for the mutation. All 3
affected individuals had juvenile onset of polycystic kidney disease and
did not develop renal failure until their second or third decade. Only 1
had aortic stenosis; none had liver involvement. Hoff et al. (2013)
suggested that the relatively milder phenotype in this family was due to
the occurrence of the mutation in the last exon.
*FIELD* RF
1. Hoff, S.; Halbritter, J.; Epting, D.; Frank, V.; Nguyen, T.-M.
T.; van Reeuwijk, J.; Boehlke, C.; Schell, C.; Yasunaga, T.; Helmstadter,
M.; Mergen, M.; Filhol, E.; and 29 others: ANKS6 is a central component
of a nephronophthisis module linking NEK8 to INVS and NPHP3. Nature
Genet. 45: 951-956, 2013.
2. Kaisaki, P. J.; Bergmann, C.; Brown, J. H.; Outeda, P.; Lens, X.
M.; Peters, D. J. M.; Gretz, N.; Gauguier, D.; Bihoreau, M.-T.: Genomic
organization and mutation screening of the human ortholog of Pkdr1
associated with polycystic kidney disease in the rat. Europ. J. Med.
Genet. 51: 325-331, 2008.
*FIELD* CN
Cassandra L. Kniffin - updated: 8/27/2013
*FIELD* CD
Patricia A. Hartz: 8/15/2013
*FIELD* ED
carol: 08/28/2013
carol: 8/28/2013
ckniffin: 8/27/2013
mgross: 8/15/2013
*RECORD*
*FIELD* NO
615370
*FIELD* TI
*615370 ANKYRIN REPEAT AND STERILE ALPHA MOTIF DOMAINS-CONTAINING PROTEIN
6; ANKS6
read more;;PKDR1;;
SAMCYSTIN
*FIELD* TX
DESCRIPTION
ANKS6 assembles a complex of ciliary proteins required for renal and
cardiovascular development (Hoff et al., 2013).
CLONING
By searching an EST database for sequences similar to rat Pkdr1, Kaisaki
et al. (2008) identified human ANKS6, which they called PKDR1. The
deduced protein contains an N-terminal ankyrin (see 612641) repeat
domain and a C-terminal sterile alpha motif (SAM) domain. Database
analysis revealed 4 possible ANKS6 isoforms.
Hoff et al. (2013) stated that the N-terminal half the deduced 871-amino
acid human ANKS6 protein contains 9 ankyrin repeats. Immunohistochemical
analysis revealed that Anks6 localized to the proximal segment of the
cilium in mouse IMCD3 innermedullary collecting duct cells.
GENE FUNCTION
Using mass spectrometry and coimmunoprecipitation analysis, Hoff et al.
(2013) found that the ciliary proteins ANKS6, NPHP3 (608002), INVS
(243305), and NEK8 (609799) interacted in a complex. The kinase domain
and a central region of NEK8 were required for interaction with human
NPHP3 and INVS and with rat Anks6. Interaction of NEK8 with NPHP3 was
enhanced by coexpression of rat Anks6. ANKS6 also interacted with HIF1AN
(606615), an oxygen sensor that hydroxylates HIF1-alpha (HIF1A; 603348)
and other ankyrin repeat proteins under normoxic conditions.
Coimmunoprecipitation experiments showed that HIF1AN facilitated
formation of a complex containing rat Anks6 and human NPHP3 and INVS.
Association of rat Anks6 with human NEK8 required hydroxylation of
Anks6. Hoff et al. (2013) concluded that oxygen-dependent hydroxylation
of ANKS6 by HIF1AN regulates the composition of the ANKS6-containing
ciliary complex.
GENE STRUCTURE
Kaisaki et al. (2008) determined that the ANKS6 gene contains 15 coding
exons and spans 64.5 kb.
MAPPING
By genomic sequence analysis, Kaisaki et al. (2008) mapped the ANKS6
gene to chromosome 9q22.33.
MOLECULAR GENETICS
In affected members of 6 unrelated families with nephronophthisis-16
(NPHP16; 615382), Hoff et al. (2013) identified 6 different homozygous
mutations in the ANKS6 gene (see, e.g., 615370.0001-615370.0005). There
were 2 truncating mutations, 2 splice site mutations, and 2 missense
mutations. ANKS6 was chosen for study based on findings in animal models
and on its interactive role of with other cilia-related proteins.
Affected individuals in 5 families had infantile onset of progressive
polycystic kidney disease leading to renal failure, whereas those in 1
family had juvenile onset of the disorder. Patients with missense
mutations showed nonenlarged cystic kidneys and no extrarenal
manifestations, whereas those with splice site and truncating mutations
had enlarged renal size and severe extrarenal defects, including
hypertrophic obstructive cardiomyopathy, aortic stenosis, pulmonary
stenosis, patent ductus arteriosus, situs inversus, and periportal liver
fibrosis. The findings indicated that ANKS6 has a role in renal and
cardiovascular development.
ANIMAL MODEL
Kaisaki et al. (2008) reported that a mutation in the SAM domain of rat
Pkdr1 causes polycystic kidney disease (see 173900).
Using antisense morpholinos, Hoff et al. (2013) found that depletion of
Anks6, Nphp3, or Nek8 in zebrafish resulted in a similar phenotype
characterized by formation of pronephric cysts and a defect in early
heart looping. In Xenopus, knockdown of Anks6, Nphp3, or Invs caused
gross body edema typical of a renal excretory defect. Knockdown of
Xenopus Anks6 or Nek8 resulted in notable simplification of proximal
pronephros convolute. Coexpression of Anks6 mRNA partially rescued
defects mediated by Nek8 knockdown, suggesting overlapping roles for
Nek8 and Anks6 during early tubular morphogenesis.
*FIELD* AV
.0001
NEPHRONOPHTHISIS 16
ANKS6, GLN441ARG
In a Serbian patient with nephronophthisis-16 (NPHP16; 615382), Hoff et
al. (2013) identified a homozygous c.1322A-G transition in exon 6 of the
ANKS6 gene, resulting in a gln441-to-arg (Q441R) substitution at a
highly conserved residue. The unaffected parents were heterozygous for
the mutation. The patient had polycystic kidney disease resulting in
chronic renal failure in early childhood, but did not have heart or
liver abnormalities. Although the Q441R mutation did not alter the
interaction of ANKS6 with other NPHP proteins or its ciliary
localization, the mutant protein was unable to rescue the renal
phenotype in Xenopus knockdown embryos, supporting its pathogenicity.
.0002
NEPHRONOPHTHISIS 16
ANKS6, IVS10AS, C-G, -3
In a patient, born of consanguineous Iranian parents, with NPHP16
(615382), Hoff et al. (2013) identified a homozygous C-to-G transition
in intron 10 of the ANKS6 gene (c.1973-3C-G), predicted to result in a
splice site mutation. The unaffected parents were heterozygous for the
mutation. The patient had polycystic kidney disease resulting in
end-stage renal disease by age 2 years and renal transplantation at age
4. The patient also had aortic and pulmonic stenosis and periportal
liver fibrosis.
.0003
NEPHRONOPHTHISIS 16
ANKS6, 11-BP DEL, NT2054
In a Danish patient with NPHP16 (615382), Hoff et al. (2013) identified
a homozygous 11-bp deletion (c.2054_2064del) in exon 11 of the ANKS6
gene, resulting in a frameshift and premature termination
(His685ProfsTer12). The unaffected parents were heterozygous for the
mutation. The patient had polycystic kidney disease resulting in
end-stage renal disease at age 1 year, aortic stenosis, periportal liver
fibrosis, and delayed psychomotor development.
.0004
NEPHRONOPHTHISIS 16
ANKS6, 3-BP DEL, 2370TCA
In an Indian patient with NPHP16 (615382), Hoff et al. (2013) identified
a homozygous 3-bp deletion (c.2370_2372delTCA) in exon 13 of the ANKS6
gene, resulting in a tyr790-to-ter (Y790X) substitution. The unaffected
parents were heterozygous for the mutation. The patient had polycystic
kidney disease resulting in end-stage renal disease at birth, aortic
stenosis, hypertrophic cardiomyopathy, patent ductus arteriosus,
cholestatic hepatopathy, and situs inversus. The infant died at age 4
months. A presumably affected sib died in utero with polycystic kidney
disease and oligohydramnios.
.0005
NEPHRONOPHTHISIS 16
ANKS6, IVS14AS, A-C, -2
In affected members of a consanguineous Turkish family with NPHP16
(615382), Hoff et al. (2013) identified a homozygous A-to-C transversion
at the acceptor splice site of intron 14 of the ANKS6 gene
(c.2512-2A-C). Each parent was heterozygous for the mutation. All 3
affected individuals had juvenile onset of polycystic kidney disease and
did not develop renal failure until their second or third decade. Only 1
had aortic stenosis; none had liver involvement. Hoff et al. (2013)
suggested that the relatively milder phenotype in this family was due to
the occurrence of the mutation in the last exon.
*FIELD* RF
1. Hoff, S.; Halbritter, J.; Epting, D.; Frank, V.; Nguyen, T.-M.
T.; van Reeuwijk, J.; Boehlke, C.; Schell, C.; Yasunaga, T.; Helmstadter,
M.; Mergen, M.; Filhol, E.; and 29 others: ANKS6 is a central component
of a nephronophthisis module linking NEK8 to INVS and NPHP3. Nature
Genet. 45: 951-956, 2013.
2. Kaisaki, P. J.; Bergmann, C.; Brown, J. H.; Outeda, P.; Lens, X.
M.; Peters, D. J. M.; Gretz, N.; Gauguier, D.; Bihoreau, M.-T.: Genomic
organization and mutation screening of the human ortholog of Pkdr1
associated with polycystic kidney disease in the rat. Europ. J. Med.
Genet. 51: 325-331, 2008.
*FIELD* CN
Cassandra L. Kniffin - updated: 8/27/2013
*FIELD* CD
Patricia A. Hartz: 8/15/2013
*FIELD* ED
carol: 08/28/2013
carol: 8/28/2013
ckniffin: 8/27/2013
mgross: 8/15/2013
MIM
615382
*RECORD*
*FIELD* NO
615382
*FIELD* TI
#615382 NEPHRONOPHTHISIS 16; NPHP16
*FIELD* TX
A number sign (#) is used with this entry because nephronophthisis-16
read more(NPHP16) is caused by homozygous mutation in the ANKS6 gene (615370) on
chromosome 9q22.
For a general phenotypic description and a discussion of genetic
heterogeneity of NPHP, see NPHP1 (256100).
CLINICAL FEATURES
Hoff et al. (2013) reported 8 patients from 6 unrelated families with
nephronophthisis. Affected individuals in 5 families had infantile onset
of progressive polycystic kidney disease leading to renal failure,
whereas those in 1 family showed juvenile onset of the disorder. Some
patients had nonenlarged cystic kidneys and no extrarenal
manifestations, whereas others had enlarged renal size and severe
extrarenal defects, including hypertrophic obstructive cardiomyopathy,
aortic stenosis, pulmonary stenosis, patent ductus arteriosus, situs
inversus, and periportal liver fibrosis.
INHERITANCE
The transmission pattern in the families with NPHP16 reported by Hoff et
al. (2013) was consistent with autosomal recessive inheritance.
MAPPING
By linkage analysis of a consanguineous Turkish family with NPHP, Hoff
et al. (2013) found linkage to an 8-Mb region spanning the ANKS6 gene on
chromosome 9 (maximum lod score of 2.41).
MOLECULAR GENETICS
In affected members of 6 unrelated families with nephronophthisis-16,
Hoff et al. (2013) identified 6 different homozygous mutations in the
ANKS6 gene (see, e.g., 615370.0001-615370.0005). There were 2 truncating
mutations, 2 splice site mutations, and 2 missense mutations. The gene
was chosen for study based on findings in animal models and on the
interactive role of ANKS6 with other cilia-related proteins. Patients
with missense mutations had no extrarenal manifestations, whereas those
with splice site and truncating mutations had additional features. The
findings indicated that the ANKS6 gene has a role in renal and
cardiovascular development.
*FIELD* RF
1. Hoff, S.; Halbritter, J.; Epting, D.; Frank, V.; Nguyen, T.-M.
T.; van Reeuwijk, J.; Boehlke, C.; Schell, C.; Yasunaga, T.; Helmstadter,
M.; Mergen, M.; Filhol, E.; and 29 others: ANKS6 is a central component
of a nephronophthisis module linking NEK8 to INVS and NPHP3. Nature
Genet. 45: 951-956, 2013.
*FIELD* CS
INHERITANCE:
Autosomal recessive
CARDIOVASCULAR:
[Heart];
Aortic stenosis (in some patients);
Pulmonic stenosis (in some patients);
Hypertrophic cardiomyopathy (in some patients);
Patent ductus arteriosus (in some patients)
ABDOMEN:
Situs inversus (in some patients);
[Liver];
Hepatic fibrosis;
Cholestasis
GENITOURINARY:
[Kidneys];
Polycystic kidney disease;
Enlarged kidneys;
Renal failure
MISCELLANEOUS:
Onset in early infancy;
Some patients show onset in childhood;
Progressive renal disorder
MOLECULAR BASIS:
Caused by mutation in the ankyrin repeat and sterile alpha motif
domains-containing protein gene 6 (ANKS6, 615370.0001)
*FIELD* CD
Cassandra L. Kniffin: 8/27/2013
*FIELD* ED
joanna: 09/16/2013
ckniffin: 8/27/2013
*FIELD* CD
Cassandra L. Kniffin: 8/27/2013
*FIELD* ED
carol: 08/28/2013
ckniffin: 8/27/2013
*RECORD*
*FIELD* NO
615382
*FIELD* TI
#615382 NEPHRONOPHTHISIS 16; NPHP16
*FIELD* TX
A number sign (#) is used with this entry because nephronophthisis-16
read more(NPHP16) is caused by homozygous mutation in the ANKS6 gene (615370) on
chromosome 9q22.
For a general phenotypic description and a discussion of genetic
heterogeneity of NPHP, see NPHP1 (256100).
CLINICAL FEATURES
Hoff et al. (2013) reported 8 patients from 6 unrelated families with
nephronophthisis. Affected individuals in 5 families had infantile onset
of progressive polycystic kidney disease leading to renal failure,
whereas those in 1 family showed juvenile onset of the disorder. Some
patients had nonenlarged cystic kidneys and no extrarenal
manifestations, whereas others had enlarged renal size and severe
extrarenal defects, including hypertrophic obstructive cardiomyopathy,
aortic stenosis, pulmonary stenosis, patent ductus arteriosus, situs
inversus, and periportal liver fibrosis.
INHERITANCE
The transmission pattern in the families with NPHP16 reported by Hoff et
al. (2013) was consistent with autosomal recessive inheritance.
MAPPING
By linkage analysis of a consanguineous Turkish family with NPHP, Hoff
et al. (2013) found linkage to an 8-Mb region spanning the ANKS6 gene on
chromosome 9 (maximum lod score of 2.41).
MOLECULAR GENETICS
In affected members of 6 unrelated families with nephronophthisis-16,
Hoff et al. (2013) identified 6 different homozygous mutations in the
ANKS6 gene (see, e.g., 615370.0001-615370.0005). There were 2 truncating
mutations, 2 splice site mutations, and 2 missense mutations. The gene
was chosen for study based on findings in animal models and on the
interactive role of ANKS6 with other cilia-related proteins. Patients
with missense mutations had no extrarenal manifestations, whereas those
with splice site and truncating mutations had additional features. The
findings indicated that the ANKS6 gene has a role in renal and
cardiovascular development.
*FIELD* RF
1. Hoff, S.; Halbritter, J.; Epting, D.; Frank, V.; Nguyen, T.-M.
T.; van Reeuwijk, J.; Boehlke, C.; Schell, C.; Yasunaga, T.; Helmstadter,
M.; Mergen, M.; Filhol, E.; and 29 others: ANKS6 is a central component
of a nephronophthisis module linking NEK8 to INVS and NPHP3. Nature
Genet. 45: 951-956, 2013.
*FIELD* CS
INHERITANCE:
Autosomal recessive
CARDIOVASCULAR:
[Heart];
Aortic stenosis (in some patients);
Pulmonic stenosis (in some patients);
Hypertrophic cardiomyopathy (in some patients);
Patent ductus arteriosus (in some patients)
ABDOMEN:
Situs inversus (in some patients);
[Liver];
Hepatic fibrosis;
Cholestasis
GENITOURINARY:
[Kidneys];
Polycystic kidney disease;
Enlarged kidneys;
Renal failure
MISCELLANEOUS:
Onset in early infancy;
Some patients show onset in childhood;
Progressive renal disorder
MOLECULAR BASIS:
Caused by mutation in the ankyrin repeat and sterile alpha motif
domains-containing protein gene 6 (ANKS6, 615370.0001)
*FIELD* CD
Cassandra L. Kniffin: 8/27/2013
*FIELD* ED
joanna: 09/16/2013
ckniffin: 8/27/2013
*FIELD* CD
Cassandra L. Kniffin: 8/27/2013
*FIELD* ED
carol: 08/28/2013
ckniffin: 8/27/2013