Full text data of SLC27A4
SLC27A4
(ACSVL4, FATP4)
[Confidence: low (only semi-automatic identification from reviews)]
Long-chain fatty acid transport protein 4; FATP-4; Fatty acid transport protein 4; 6.2.1.- (Solute carrier family 27 member 4)
Long-chain fatty acid transport protein 4; FATP-4; Fatty acid transport protein 4; 6.2.1.- (Solute carrier family 27 member 4)
UniProt
Q6P1M0
ID S27A4_HUMAN Reviewed; 643 AA.
AC Q6P1M0; A8K2F7; O95186;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-JUL-2004, sequence version 1.
DT 22-JAN-2014, entry version 101.
DE RecName: Full=Long-chain fatty acid transport protein 4;
DE Short=FATP-4;
DE Short=Fatty acid transport protein 4;
DE EC=6.2.1.-;
DE AltName: Full=Solute carrier family 27 member 4;
GN Name=SLC27A4; Synonyms=ACSVL4, FATP4;
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 [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Heart;
RX PubMed=9878842; DOI=10.1016/S0167-4781(98)00231-0;
RA Fitscher B.A., Riedel H.D., Young K.C., Stremmel W.;
RT "Tissue distribution and cDNA cloning of a human fatty acid transport
RT protein (hsFATP4).";
RL Biochim. Biophys. Acta 1443:381-385(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thalamus;
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 [3]
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP VARIANT SER-209.
RX PubMed=14715877; DOI=10.1210/jc.2003-030682;
RA Gertow K., Bellanda M., Eriksson P., Boquist S., Hamsten A.,
RA Sunnerhagen M., Fisher R.M.;
RT "Genetic and structural evaluation of fatty acid transport protein-4
RT in relation to markers of the insulin resistance syndrome.";
RL J. Clin. Endocrinol. Metab. 89:392-399(2004).
RN [8]
RP VARIANTS IPS THR-92; PRO-247; ARG-300 AND HIS-583.
RX PubMed=19631310; DOI=10.1016/j.ajhg.2009.06.021;
RA Klar J., Schweiger M., Zimmerman R., Zechner R., Li H., Torma H.,
RA Vahlquist A., Bouadjar B., Dahl N., Fischer J.;
RT "Mutations in the fatty acid transport protein 4 gene cause the
RT ichthyosis prematurity syndrome.";
RL Am. J. Hum. Genet. 85:248-253(2009).
RN [9]
RP VARIANT IPS CYS-374.
RX PubMed=20815031; DOI=10.1002/ajmg.a.33648;
RA Morice-Picard F., Leaute-Labreze C., Decor A., Boralevi F.,
RA Lacombe D., Taieb A., Fischer J.;
RT "A novel mutation in the fatty acid transport protein 4 gene in a
RT patient initially described as affected by self-healing congenital
RT verruciform hyperkeratosis.";
RL Am. J. Med. Genet. A 152:2664-2665(2010).
CC -!- FUNCTION: Involved in translocation of long-chain fatty acids
CC (LFCA) across the plasma membrane. Appears to be the principal
CC fatty acid transporter in small intestinal enterocytes. Plays a
CC role in the formation of the epidermal barrier. Required for fat
CC absorption in early embryogenesis. Has acyl-CoA ligase activity
CC for long-chain and very-long-chain fatty acids (VLCFAs).
CC Indirectly inhibits RPE65 via substrate competition and via
CC production of VLCFA derivatives like lignoceroyl-CoA. Prevents
CC light-induced degeneration of rods and cones (By similarity).
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein
CC (Probable). Endoplasmic reticulum membrane (By similarity).
CC -!- TISSUE SPECIFICITY: Expressed at highest levels in brain, testis,
CC colon and kidney. Expressed at medium levels in heart and liver,
CC small intestine and stomach. Expressed at low levels in peripheral
CC leukocytes, bone marrow, skeletal muscle and aorta. Expressed in
CC adipose tissue.
CC -!- DISEASE: Ichthyosis prematurity syndrome (IPS) [MIM:608649]: A
CC keratinization disorder characterized by complications in the
CC second trimester of pregnancy resulting from polyhydramnion, with
CC premature birth of a child with thick caseous desquamating
CC epidermis, respiratory complications and transient eosinophilia.
CC After recovery during the first months of life, the symptoms are
CC relatively benign and the patients suffer from a lifelong non-
CC scaly ichthyosis with atopic manifestations. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: SLC27A4/FATP4-mediated fatty acid uptake is
CC associated to paramaters related to insulin resistance, which is
CC associated with disturbed fatty acid metabolism and homeostasis,
CC such as obesity. SLC27A4/FATP4 expression is positively correlated
CC with acquired obesity.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme
CC family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD11623.1; Type=Frameshift; Positions=362, 387, 612, 619;
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DR EMBL; AF055899; AAD11623.1; ALT_FRAME; mRNA.
DR EMBL; AK290222; BAF82911.1; -; mRNA.
DR EMBL; AL359091; CAI13490.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW87779.1; -; Genomic_DNA.
DR EMBL; BC065003; AAH65003.1; -; mRNA.
DR RefSeq; NP_005085.2; NM_005094.3.
DR UniGene; Hs.656699; -.
DR ProteinModelPortal; Q6P1M0; -.
DR SMR; Q6P1M0; 79-615.
DR IntAct; Q6P1M0; 4.
DR MINT; MINT-8376036; -.
DR STRING; 9606.ENSP00000300456; -.
DR BindingDB; Q6P1M0; -.
DR ChEMBL; CHEMBL4327; -.
DR TCDB; 4.C.1.1.10; the proposed fatty acid transporter (fat) family.
DR PhosphoSite; Q6P1M0; -.
DR DMDM; 74749065; -.
DR PaxDb; Q6P1M0; -.
DR PRIDE; Q6P1M0; -.
DR Ensembl; ENST00000300456; ENSP00000300456; ENSG00000167114.
DR GeneID; 10999; -.
DR KEGG; hsa:10999; -.
DR UCSC; uc004but.3; human.
DR CTD; 10999; -.
DR GeneCards; GC09P131102; -.
DR HGNC; HGNC:10998; SLC27A4.
DR HPA; CAB009771; -.
DR HPA; HPA007293; -.
DR MIM; 604194; gene.
DR MIM; 608649; phenotype.
DR neXtProt; NX_Q6P1M0; -.
DR Orphanet; 88621; Ichthyosis prematurity syndrome.
DR PharmGKB; PA35872; -.
DR eggNOG; COG0318; -.
DR HOGENOM; HOG000044189; -.
DR HOVERGEN; HBG005642; -.
DR InParanoid; Q6P1M0; -.
DR KO; K08745; -.
DR OMA; VMYDCLP; -.
DR OrthoDB; EOG7W6WKB; -.
DR PhylomeDB; Q6P1M0; -.
DR BRENDA; 6.2.1.3; 2681.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR GeneWiki; SLC27A4; -.
DR GenomeRNAi; 10999; -.
DR NextBio; 41787; -.
DR PRO; PR:Q6P1M0; -.
DR ArrayExpress; Q6P1M0; -.
DR Bgee; Q6P1M0; -.
DR CleanEx; HS_SLC27A4; -.
DR Genevestigator; Q6P1M0; -.
DR GO; GO:0031526; C:brush border membrane; IEA:Ensembl.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005902; C:microvillus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0015245; F:fatty acid transporter activity; TAS:ProtInc.
DR GO; GO:0004467; F:long-chain fatty acid-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0031957; F:very long-chain fatty acid-CoA ligase activity; IEA:Ensembl.
DR GO; GO:0044539; P:long-chain fatty acid import; IDA:UniProtKB.
DR GO; GO:0001579; P:medium-chain fatty acid transport; IEA:Ensembl.
DR GO; GO:0043588; P:skin development; IEA:Ensembl.
DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
DR GO; GO:0042760; P:very long-chain fatty acid catabolic process; IEA:Ensembl.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR022272; Lipocalin_CS.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Disease mutation; Endoplasmic reticulum;
KW Fatty acid metabolism; Ichthyosis; Ligase; Lipid metabolism;
KW Lipid transport; Membrane; Nucleotide-binding; Polymorphism;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1 643 Long-chain fatty acid transport protein
FT 4.
FT /FTId=PRO_0000193209.
FT TRANSMEM 20 42 Helical; (Potential).
FT TRANSMEM 139 156 Helical; (Potential).
FT NP_BIND 243 254 AMP (Potential).
FT VARIANT 92 92 A -> T (in IPS).
FT /FTId=VAR_063192.
FT VARIANT 209 209 G -> S (correlates with lower body mass
FT index, triglyceride concentrations,
FT systolic blood pressure, insulin
FT concentrations and homeostasis model
FT assessment index; dbSNP:rs2240953).
FT /FTId=VAR_023783.
FT VARIANT 247 247 S -> P (in IPS).
FT /FTId=VAR_063193.
FT VARIANT 300 300 Q -> R (in IPS).
FT /FTId=VAR_063194.
FT VARIANT 374 374 R -> C (in IPS).
FT /FTId=VAR_064500.
FT VARIANT 583 583 R -> H (in IPS).
FT /FTId=VAR_063195.
FT CONFLICT 194 194 L -> P (in Ref. 1; AAD11623).
FT CONFLICT 605 605 G -> A (in Ref. 1; AAD11623).
SQ SEQUENCE 643 AA; 72064 MW; 95E677DB3CEB9A14 CRC64;
MLLGASLVGV LLFSKLVLKL PWTQVGFSLL FLYLGSGGWR FIRVFIKTIR RDIFGGLVLL
KVKAKVRQCL QERRTVPILF ASTVRRHPDK TALIFEGTDT HWTFRQLDEY SSSVANFLQA
RGLASGDVAA IFMENRNEFV GLWLGMAKLG VEAALINTNL RRDALLHCLT TSRARALVFG
SEMASAICEV HASLDPSLSL FCSGSWEPGA VPPSTEHLDP LLKDAPKHLP SCPDKGFTDK
LFYIYTSGTT GLPKAAIVVH SRYYRMAALV YYGFRMRPND IVYDCLPLYH SAGNIVGIGQ
CLLHGMTVVI RKKFSASRFW DDCIKYNCTI VQYIGELCRY LLNQPPREAE NQHQVRMALG
NGLRQSIWTN FSSRFHIPQV AEFYGATECN CSLGNFDSQV GACGFNSRIL SFVYPIRLVR
VNEDTMELIR GPDGVCIPCQ PGEPGQLVGR IIQKDPLRRF DGYLNQGANN KKIAKDVFKK
GDQAYLTGDV LVMDELGYLY FRDRTGDTFR WKGENVSTTE VEGTLSRLLD MADVAVYGVE
VPGTEGRAGM AAVASPTGNC DLERFAQVLE KELPLYARPI FLRLLPELHK TGTYKFQKTE
LRKEGFDPAI VKDPLFYLDA QKGRYVPLDQ EAYSRIQAGE EKL
//
ID S27A4_HUMAN Reviewed; 643 AA.
AC Q6P1M0; A8K2F7; O95186;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-JUL-2004, sequence version 1.
DT 22-JAN-2014, entry version 101.
DE RecName: Full=Long-chain fatty acid transport protein 4;
DE Short=FATP-4;
DE Short=Fatty acid transport protein 4;
DE EC=6.2.1.-;
DE AltName: Full=Solute carrier family 27 member 4;
GN Name=SLC27A4; Synonyms=ACSVL4, FATP4;
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 [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Heart;
RX PubMed=9878842; DOI=10.1016/S0167-4781(98)00231-0;
RA Fitscher B.A., Riedel H.D., Young K.C., Stremmel W.;
RT "Tissue distribution and cDNA cloning of a human fatty acid transport
RT protein (hsFATP4).";
RL Biochim. Biophys. Acta 1443:381-385(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thalamus;
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 [3]
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP VARIANT SER-209.
RX PubMed=14715877; DOI=10.1210/jc.2003-030682;
RA Gertow K., Bellanda M., Eriksson P., Boquist S., Hamsten A.,
RA Sunnerhagen M., Fisher R.M.;
RT "Genetic and structural evaluation of fatty acid transport protein-4
RT in relation to markers of the insulin resistance syndrome.";
RL J. Clin. Endocrinol. Metab. 89:392-399(2004).
RN [8]
RP VARIANTS IPS THR-92; PRO-247; ARG-300 AND HIS-583.
RX PubMed=19631310; DOI=10.1016/j.ajhg.2009.06.021;
RA Klar J., Schweiger M., Zimmerman R., Zechner R., Li H., Torma H.,
RA Vahlquist A., Bouadjar B., Dahl N., Fischer J.;
RT "Mutations in the fatty acid transport protein 4 gene cause the
RT ichthyosis prematurity syndrome.";
RL Am. J. Hum. Genet. 85:248-253(2009).
RN [9]
RP VARIANT IPS CYS-374.
RX PubMed=20815031; DOI=10.1002/ajmg.a.33648;
RA Morice-Picard F., Leaute-Labreze C., Decor A., Boralevi F.,
RA Lacombe D., Taieb A., Fischer J.;
RT "A novel mutation in the fatty acid transport protein 4 gene in a
RT patient initially described as affected by self-healing congenital
RT verruciform hyperkeratosis.";
RL Am. J. Med. Genet. A 152:2664-2665(2010).
CC -!- FUNCTION: Involved in translocation of long-chain fatty acids
CC (LFCA) across the plasma membrane. Appears to be the principal
CC fatty acid transporter in small intestinal enterocytes. Plays a
CC role in the formation of the epidermal barrier. Required for fat
CC absorption in early embryogenesis. Has acyl-CoA ligase activity
CC for long-chain and very-long-chain fatty acids (VLCFAs).
CC Indirectly inhibits RPE65 via substrate competition and via
CC production of VLCFA derivatives like lignoceroyl-CoA. Prevents
CC light-induced degeneration of rods and cones (By similarity).
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein
CC (Probable). Endoplasmic reticulum membrane (By similarity).
CC -!- TISSUE SPECIFICITY: Expressed at highest levels in brain, testis,
CC colon and kidney. Expressed at medium levels in heart and liver,
CC small intestine and stomach. Expressed at low levels in peripheral
CC leukocytes, bone marrow, skeletal muscle and aorta. Expressed in
CC adipose tissue.
CC -!- DISEASE: Ichthyosis prematurity syndrome (IPS) [MIM:608649]: A
CC keratinization disorder characterized by complications in the
CC second trimester of pregnancy resulting from polyhydramnion, with
CC premature birth of a child with thick caseous desquamating
CC epidermis, respiratory complications and transient eosinophilia.
CC After recovery during the first months of life, the symptoms are
CC relatively benign and the patients suffer from a lifelong non-
CC scaly ichthyosis with atopic manifestations. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: SLC27A4/FATP4-mediated fatty acid uptake is
CC associated to paramaters related to insulin resistance, which is
CC associated with disturbed fatty acid metabolism and homeostasis,
CC such as obesity. SLC27A4/FATP4 expression is positively correlated
CC with acquired obesity.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme
CC family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD11623.1; Type=Frameshift; Positions=362, 387, 612, 619;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; AF055899; AAD11623.1; ALT_FRAME; mRNA.
DR EMBL; AK290222; BAF82911.1; -; mRNA.
DR EMBL; AL359091; CAI13490.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW87779.1; -; Genomic_DNA.
DR EMBL; BC065003; AAH65003.1; -; mRNA.
DR RefSeq; NP_005085.2; NM_005094.3.
DR UniGene; Hs.656699; -.
DR ProteinModelPortal; Q6P1M0; -.
DR SMR; Q6P1M0; 79-615.
DR IntAct; Q6P1M0; 4.
DR MINT; MINT-8376036; -.
DR STRING; 9606.ENSP00000300456; -.
DR BindingDB; Q6P1M0; -.
DR ChEMBL; CHEMBL4327; -.
DR TCDB; 4.C.1.1.10; the proposed fatty acid transporter (fat) family.
DR PhosphoSite; Q6P1M0; -.
DR DMDM; 74749065; -.
DR PaxDb; Q6P1M0; -.
DR PRIDE; Q6P1M0; -.
DR Ensembl; ENST00000300456; ENSP00000300456; ENSG00000167114.
DR GeneID; 10999; -.
DR KEGG; hsa:10999; -.
DR UCSC; uc004but.3; human.
DR CTD; 10999; -.
DR GeneCards; GC09P131102; -.
DR HGNC; HGNC:10998; SLC27A4.
DR HPA; CAB009771; -.
DR HPA; HPA007293; -.
DR MIM; 604194; gene.
DR MIM; 608649; phenotype.
DR neXtProt; NX_Q6P1M0; -.
DR Orphanet; 88621; Ichthyosis prematurity syndrome.
DR PharmGKB; PA35872; -.
DR eggNOG; COG0318; -.
DR HOGENOM; HOG000044189; -.
DR HOVERGEN; HBG005642; -.
DR InParanoid; Q6P1M0; -.
DR KO; K08745; -.
DR OMA; VMYDCLP; -.
DR OrthoDB; EOG7W6WKB; -.
DR PhylomeDB; Q6P1M0; -.
DR BRENDA; 6.2.1.3; 2681.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR GeneWiki; SLC27A4; -.
DR GenomeRNAi; 10999; -.
DR NextBio; 41787; -.
DR PRO; PR:Q6P1M0; -.
DR ArrayExpress; Q6P1M0; -.
DR Bgee; Q6P1M0; -.
DR CleanEx; HS_SLC27A4; -.
DR Genevestigator; Q6P1M0; -.
DR GO; GO:0031526; C:brush border membrane; IEA:Ensembl.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005902; C:microvillus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0015245; F:fatty acid transporter activity; TAS:ProtInc.
DR GO; GO:0004467; F:long-chain fatty acid-CoA ligase activity; IDA:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0031957; F:very long-chain fatty acid-CoA ligase activity; IEA:Ensembl.
DR GO; GO:0044539; P:long-chain fatty acid import; IDA:UniProtKB.
DR GO; GO:0001579; P:medium-chain fatty acid transport; IEA:Ensembl.
DR GO; GO:0043588; P:skin development; IEA:Ensembl.
DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
DR GO; GO:0042760; P:very long-chain fatty acid catabolic process; IEA:Ensembl.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR022272; Lipocalin_CS.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Disease mutation; Endoplasmic reticulum;
KW Fatty acid metabolism; Ichthyosis; Ligase; Lipid metabolism;
KW Lipid transport; Membrane; Nucleotide-binding; Polymorphism;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1 643 Long-chain fatty acid transport protein
FT 4.
FT /FTId=PRO_0000193209.
FT TRANSMEM 20 42 Helical; (Potential).
FT TRANSMEM 139 156 Helical; (Potential).
FT NP_BIND 243 254 AMP (Potential).
FT VARIANT 92 92 A -> T (in IPS).
FT /FTId=VAR_063192.
FT VARIANT 209 209 G -> S (correlates with lower body mass
FT index, triglyceride concentrations,
FT systolic blood pressure, insulin
FT concentrations and homeostasis model
FT assessment index; dbSNP:rs2240953).
FT /FTId=VAR_023783.
FT VARIANT 247 247 S -> P (in IPS).
FT /FTId=VAR_063193.
FT VARIANT 300 300 Q -> R (in IPS).
FT /FTId=VAR_063194.
FT VARIANT 374 374 R -> C (in IPS).
FT /FTId=VAR_064500.
FT VARIANT 583 583 R -> H (in IPS).
FT /FTId=VAR_063195.
FT CONFLICT 194 194 L -> P (in Ref. 1; AAD11623).
FT CONFLICT 605 605 G -> A (in Ref. 1; AAD11623).
SQ SEQUENCE 643 AA; 72064 MW; 95E677DB3CEB9A14 CRC64;
MLLGASLVGV LLFSKLVLKL PWTQVGFSLL FLYLGSGGWR FIRVFIKTIR RDIFGGLVLL
KVKAKVRQCL QERRTVPILF ASTVRRHPDK TALIFEGTDT HWTFRQLDEY SSSVANFLQA
RGLASGDVAA IFMENRNEFV GLWLGMAKLG VEAALINTNL RRDALLHCLT TSRARALVFG
SEMASAICEV HASLDPSLSL FCSGSWEPGA VPPSTEHLDP LLKDAPKHLP SCPDKGFTDK
LFYIYTSGTT GLPKAAIVVH SRYYRMAALV YYGFRMRPND IVYDCLPLYH SAGNIVGIGQ
CLLHGMTVVI RKKFSASRFW DDCIKYNCTI VQYIGELCRY LLNQPPREAE NQHQVRMALG
NGLRQSIWTN FSSRFHIPQV AEFYGATECN CSLGNFDSQV GACGFNSRIL SFVYPIRLVR
VNEDTMELIR GPDGVCIPCQ PGEPGQLVGR IIQKDPLRRF DGYLNQGANN KKIAKDVFKK
GDQAYLTGDV LVMDELGYLY FRDRTGDTFR WKGENVSTTE VEGTLSRLLD MADVAVYGVE
VPGTEGRAGM AAVASPTGNC DLERFAQVLE KELPLYARPI FLRLLPELHK TGTYKFQKTE
LRKEGFDPAI VKDPLFYLDA QKGRYVPLDQ EAYSRIQAGE EKL
//
MIM
604194
*RECORD*
*FIELD* NO
604194
*FIELD* TI
*604194 SOLUTE CARRIER FAMILY 27 (FATTY ACID TRANSPORTER), MEMBER 4; SLC27A4
;;FATTY ACID TRANSPORT PROTEIN 4; FATP4;;
read moreACYL-CoA SYNTHETASE VERY LONG CHAIN FAMILY, MEMBER 5; ACSVL5
*FIELD* TX
CLONING
Using an expression cloning strategy, Schaffer and Lodish (1994)
identified a membrane protein, which they termed fatty acid transport
protein, or FATP (SLC27A1; 600691), from murine adipocytes. FATP
facilitates the uptake of long chain fatty acids. Hirsch et al. (1998)
identified a large family of FATPs characterized by the presence of an
FATP signature sequence. They identified 5 distinct FATPs in mouse and 6
different FATPs in human, which they designated FATP1 (SLC27A1; 600691),
-2 (SLC27A2; 603247), -3 (SLC27A3; 604193), -4 (SLC27A4), -5 (SLC27A5;
603314), and -6 (SLC27A6; 604196). Human and mouse FATPs have unique
expression patterns and are found in major organs of fatty acid
metabolism, such as adipose tissue, liver, heart, and kidney.
By database analysis, Watkins et al. (2007) identified SLC27A4, which
they called ACSVL5. The deduced 643-amino acid protein contains all 5
motifs characteristic of acyl-CoA synthetases. Phylogenetic analysis
revealed that ACSVL5 belongs to a family of very long chain acyl-CoA
synthetases.
GENE STRUCTURE
Gertow et al. (2004) stated that the FATP4 gene contains 12 coding exons
spanning more than 17 kb of genomic DNA. Watkins et al. (2007)
determined that the SLC27A4 gene contains 13 exons.
MAPPING
Gertow et al. (2004) stated that the FATP4 gene maps to chromosome 9q34.
Watkins et al. (2007) mapped the SLC27A4 gene to the plus strand of
chromosome 9q34.11 by genomic sequence analysis.
GENE FUNCTION
Stahl et al. (1999) showed that FATP4 is expressed at high levels on the
apical side of mature enterocytes in the small intestine. Furthermore,
overexpression of FATP4 in 293 cells facilitated uptake of long chain
fatty acids with the same specificity as enterocytes, while reduction of
FATP4 expression in primary enterocytes by antisense oligonucleotides
inhibited fatty acid uptake by 50%. These results suggested that FATP4
is the principal fatty acid transporter in enterocytes and may
constitute a novel target for antiobesity therapy.
Klar et al. (2009) demonstrated that FATP4 deficiency in human
fibroblasts is associated with reduced VLCFA-CoA synthetase activity and
a reduced incorporation of VLCFA into neutral and polar lipids.
MOLECULAR GENETICS
- Ichthyosis Prematurity Syndrome
Klar et al. (2009) performed sequence analysis of the FATP4 gene in a
North African family, a Middle Eastern family, and 18 families of
Scandinavian origin segregating ichthyosis prematurity syndrome (IPS;
608649). They identified 7 different mutations. All affected members of
the Scandinavian families were homozygous or compound heterozygous for a
nonsense mutation (C168X; 604194.0001), indicating a founder effect. A
splice site mutation (604194.0002) and a missense mutation (604194.0007)
were identified in homozygosity in affected members of the North African
and the Middle Eastern families, respectively. None of the mutations
were found in 120 healthy control individuals.
- Insulin Resistance Syndrome
Gertow et al. (2004) investigated polymorphisms in the FATP4 gene with
respect to associations with fasting and postprandial lipid and
lipoprotein variables and markers of insulin resistance in 608 healthy,
middle-aged Swedish men. Heterozygotes for a gly209-to-ser (G209S)
polymorphism (ser allele frequency 0.05) had significantly lower body
mass index (BMI) and, correcting for BMI, significantly lower
triglyceride concentrations, systolic blood pressure, insulin
concentrations, and homeostasis model assessment index compared with
common (G209) homozygotes. A 3-dimensional model of the FATP4 protein
revealed that the variable residue 209 is exposed in a region
potentially involved in protein-protein interactions. Furthermore, the
model indicated functional regions with respect to nonesterified fatty
acid (NEFA) transport and acyl-coenzyme A synthase activity and membrane
association. Gertow et al. (2004) concluded that these findings proposed
FATP4 as a candidate gene for the insulin resistance syndrome (see
605552) and provided a structural basis for understanding FATP function
in NEFA transport and metabolism.
ANIMAL MODEL
Moulson et al. (2003) discovered a spontaneous autosomal recessive
mutation in their mouse colony causing extremely tight, thick skin. They
named the mutation 'wrinkle-free' (wrfr). The wrfr phenotype is similar
to that of restrictive dermopathy in humans (275210). Newborn wrfr -/-
mice have difficulty breathing because of the tight skin, do not suckle,
exhibit a defective skin barrier, and die several hours after birth.
There are also defects in the hair follicle morphogenesis and hair
growth. Moulson et al. (2003) reported positional cloning of the wrfr
gene, revealing a retrotransposon insertion into a coding exon of
Slc27a4, the gene encoding the fatty acid transport protein FATP4. FATP4
is the primary intestinal fatty acid transport protein and is thought to
play a major role in dietary fatty acid uptake. It has therefore been
viewed as a target to prevent or reverse obesity. However, its function
in vivo had not been determined. The findings of Moulson et al. (2003)
demonstrated an unexpected yet critical role of FATP4 in skin and hair
development and suggested that SLC27A4 is a candidate gene for
restrictive dermopathy.
*FIELD* AV
.0001
ICHTHYOSIS PREMATURITY SYNDROME
SLC27A4, CYS168TER
In affected members of 18 Scandinavian families segregating ichthyosis
prematurity syndrome (608649), Klar et al. (2009) identified
homozygosity or compound heterozygosity for a 504C-A transversion in
exon 3 of the SLC27A4 gene, resulting in a cys168-to-ter (C168X)
substitution. This finding indicates that C168X is a founder mutation.
Klar et al. (2009) demonstrated absence of full-length SLC27A4 in an IPS
patient homozygous for the mutation. The mutation was not found in 120
healthy control individuals.
.0002
ICHTHYOSIS PREMATURITY SYNDROME
SLC27A4, IVS4AS, G-A, -1
In a North African patient with ichthyosis prematurity syndrome
(608649), daughter to consanguineous parents, Klar et al. (2009)
identified a homozygous acceptor splice site mutation for exon 5
(716-1G-A) in the SLC27A4 gene, predicting a truncated protein.
.0003
ICHTHYOSIS PREMATURITY SYNDROME
SLC27A4, ALA92THR
In affected members of Scandinavian families segregating ichthyosis
prematurity syndrome (608649), Klar et al. (2009) identified compound
heterozygosity for mutations in the SLC27A4 gene: C168X (604194.0001)
and a 274G-A transition in exon 3, resulting in an ala92-to-thr (A92T)
substitution.
.0004
ICHTHYOSIS PREMATURITY SYNDROME
SLC27A4, SER247PRO
In affected members of Scandinavian families segregating ichthyosis
prematurity syndrome (608649), Klar et al. (2009) identified compound
heterozygosity for mutations in the SLC27A4 gene: C168X (604194.0001)
and a 739T-C transition in exon 5, resulting in a ser247-to-pro (S247P)
substitution in the highly conserved AMP-binding domain.
.0005
ICHTHYOSIS PREMATURITY SYNDROME
SLC27A4, GLN300ARG
In affected members of Scandinavian families segregating ichthyosis
prematurity syndrome (608649), Klar et al. (2009) identified compound
heterozygosity for mutations in the SLC27A4 gene: C168X (604194.0001)
and an 899A-G transition in exon 7, resulting in a gln300-to-arg (Q300R)
substitution in the highly conserved AMP-binding domain.
.0006
ICHTHYOSIS PREMATURITY SYNDROME
SLC27A4, IVS7AS, A-G, -2
In affected members of Scandinavian families segregating ichthyosis
prematurity syndrome (608649), Klar et al. (2009) identified compound
heterozygosity for mutations in the SLC27A4 gene: C168X (604194.0001)
and a 988-2A-G splice site mutation.
.0007
ICHTHYOSIS PREMATURITY SYNDROME
SLC27A4, ARG583HIS
In affected members of a Middle Eastern family with ichthyosis
prematurity syndrome (608649), Klar et al. (2009) identified
homozygosity for a 1748G-A transition in exon 12 of the SLC27A4 gene,
resulting in an arg583-to-his (R483H) mutation in the C-terminal domain.
*FIELD* RF
1. Gertow, K.; Bellanda, M.; Eriksson, P.; Boquist, S.; Hamsten, A.;
Sunnerhagen, M.; Fisher, R. M.: Genetic and structural evaluation
of fatty acid transport protein-4 in relation to markers of the insulin
resistance syndrome. J. Clin. Endocr. Metab. 89: 392-399, 2004.
2. Hirsch, D.; Stahl, A.; Lodish, H. F.: A family of fatty acid transporters
conserved from mycobacterium to man. Proc. Nat. Acad. Sci. 95: 8625-8629,
1998.
3. Klar, J.; Schweiger, M.; Zimmerman, R.; Zechner, R.; Li, H.; Torma,
H.; Vahlquist, A.; Bouadjar, B.; Dahl. N.; Fischer, J.: Mutations
in the fatty acid transport protein 4 gene cause the ichthyosis prematurity
syndrome. Am. J. Hum. Genet. 85: 248-253, 2009.
4. Moulson, C. L.; Martin, D. R.; Lugus, J. J.; Schaffer, J. E.; Lind,
A. C.; Miner, J. H.: Cloning of wrinkle-free, a previously uncharacterized
mouse mutation, reveals crucial roles for fatty acid transport protein
4 in skin and hair development. Proc. Nat. Acad. Sci. 100: 5274-5279,
2003.
5. Schaffer, J. E.; Lodish, H. F.: Expression cloning and characterization
of a novel adipocyte long chain fatty acid transport protein. Cell 79:
427-436, 1994.
6. Stahl, A.; Hirsch, D. J.; Gimeno, R. E.; Punreddy, S.; Ge, P.;
Watson, N.; Patel, S.; Kotler, M.; Raimondi, A.; Tartaglia, L. A.;
Lodish, H. F.: Identification of the major intestinal fatty acid
transport protein. Molec. Cell 4: 299-308, 1999.
7. Watkins, P. A.; Maiguel, D.; Jia, Z.; Pevsner, J.: Evidence for
26 distinct acyl-coenzyme A synthetase genes in the human genome. J.
Lipid Res. 48: 2736-2750, 2007.
*FIELD* CN
Patricia A. Hartz - updated: 10/4/2011
Nara Sobreira - updated: 10/7/2009
John A. Phillips, III - updated: 1/2/2007
Victor A. McKusick - updated: 6/13/2003
Carol A. Bocchini - updated: 4/8/2003
Stylianos E. Antonarakis - updated: 10/25/1999
*FIELD* CD
Stylianos E. Antonarakis: 9/28/1999
*FIELD* ED
mgross: 11/30/2011
terry: 10/4/2011
terry: 5/28/2010
carol: 2/16/2010
carol: 10/8/2009
terry: 10/7/2009
alopez: 1/2/2007
alopez: 6/23/2003
terry: 6/13/2003
carol: 4/8/2003
mgross: 10/10/2002
mgross: 10/25/1999
mgross: 9/28/1999
*RECORD*
*FIELD* NO
604194
*FIELD* TI
*604194 SOLUTE CARRIER FAMILY 27 (FATTY ACID TRANSPORTER), MEMBER 4; SLC27A4
;;FATTY ACID TRANSPORT PROTEIN 4; FATP4;;
read moreACYL-CoA SYNTHETASE VERY LONG CHAIN FAMILY, MEMBER 5; ACSVL5
*FIELD* TX
CLONING
Using an expression cloning strategy, Schaffer and Lodish (1994)
identified a membrane protein, which they termed fatty acid transport
protein, or FATP (SLC27A1; 600691), from murine adipocytes. FATP
facilitates the uptake of long chain fatty acids. Hirsch et al. (1998)
identified a large family of FATPs characterized by the presence of an
FATP signature sequence. They identified 5 distinct FATPs in mouse and 6
different FATPs in human, which they designated FATP1 (SLC27A1; 600691),
-2 (SLC27A2; 603247), -3 (SLC27A3; 604193), -4 (SLC27A4), -5 (SLC27A5;
603314), and -6 (SLC27A6; 604196). Human and mouse FATPs have unique
expression patterns and are found in major organs of fatty acid
metabolism, such as adipose tissue, liver, heart, and kidney.
By database analysis, Watkins et al. (2007) identified SLC27A4, which
they called ACSVL5. The deduced 643-amino acid protein contains all 5
motifs characteristic of acyl-CoA synthetases. Phylogenetic analysis
revealed that ACSVL5 belongs to a family of very long chain acyl-CoA
synthetases.
GENE STRUCTURE
Gertow et al. (2004) stated that the FATP4 gene contains 12 coding exons
spanning more than 17 kb of genomic DNA. Watkins et al. (2007)
determined that the SLC27A4 gene contains 13 exons.
MAPPING
Gertow et al. (2004) stated that the FATP4 gene maps to chromosome 9q34.
Watkins et al. (2007) mapped the SLC27A4 gene to the plus strand of
chromosome 9q34.11 by genomic sequence analysis.
GENE FUNCTION
Stahl et al. (1999) showed that FATP4 is expressed at high levels on the
apical side of mature enterocytes in the small intestine. Furthermore,
overexpression of FATP4 in 293 cells facilitated uptake of long chain
fatty acids with the same specificity as enterocytes, while reduction of
FATP4 expression in primary enterocytes by antisense oligonucleotides
inhibited fatty acid uptake by 50%. These results suggested that FATP4
is the principal fatty acid transporter in enterocytes and may
constitute a novel target for antiobesity therapy.
Klar et al. (2009) demonstrated that FATP4 deficiency in human
fibroblasts is associated with reduced VLCFA-CoA synthetase activity and
a reduced incorporation of VLCFA into neutral and polar lipids.
MOLECULAR GENETICS
- Ichthyosis Prematurity Syndrome
Klar et al. (2009) performed sequence analysis of the FATP4 gene in a
North African family, a Middle Eastern family, and 18 families of
Scandinavian origin segregating ichthyosis prematurity syndrome (IPS;
608649). They identified 7 different mutations. All affected members of
the Scandinavian families were homozygous or compound heterozygous for a
nonsense mutation (C168X; 604194.0001), indicating a founder effect. A
splice site mutation (604194.0002) and a missense mutation (604194.0007)
were identified in homozygosity in affected members of the North African
and the Middle Eastern families, respectively. None of the mutations
were found in 120 healthy control individuals.
- Insulin Resistance Syndrome
Gertow et al. (2004) investigated polymorphisms in the FATP4 gene with
respect to associations with fasting and postprandial lipid and
lipoprotein variables and markers of insulin resistance in 608 healthy,
middle-aged Swedish men. Heterozygotes for a gly209-to-ser (G209S)
polymorphism (ser allele frequency 0.05) had significantly lower body
mass index (BMI) and, correcting for BMI, significantly lower
triglyceride concentrations, systolic blood pressure, insulin
concentrations, and homeostasis model assessment index compared with
common (G209) homozygotes. A 3-dimensional model of the FATP4 protein
revealed that the variable residue 209 is exposed in a region
potentially involved in protein-protein interactions. Furthermore, the
model indicated functional regions with respect to nonesterified fatty
acid (NEFA) transport and acyl-coenzyme A synthase activity and membrane
association. Gertow et al. (2004) concluded that these findings proposed
FATP4 as a candidate gene for the insulin resistance syndrome (see
605552) and provided a structural basis for understanding FATP function
in NEFA transport and metabolism.
ANIMAL MODEL
Moulson et al. (2003) discovered a spontaneous autosomal recessive
mutation in their mouse colony causing extremely tight, thick skin. They
named the mutation 'wrinkle-free' (wrfr). The wrfr phenotype is similar
to that of restrictive dermopathy in humans (275210). Newborn wrfr -/-
mice have difficulty breathing because of the tight skin, do not suckle,
exhibit a defective skin barrier, and die several hours after birth.
There are also defects in the hair follicle morphogenesis and hair
growth. Moulson et al. (2003) reported positional cloning of the wrfr
gene, revealing a retrotransposon insertion into a coding exon of
Slc27a4, the gene encoding the fatty acid transport protein FATP4. FATP4
is the primary intestinal fatty acid transport protein and is thought to
play a major role in dietary fatty acid uptake. It has therefore been
viewed as a target to prevent or reverse obesity. However, its function
in vivo had not been determined. The findings of Moulson et al. (2003)
demonstrated an unexpected yet critical role of FATP4 in skin and hair
development and suggested that SLC27A4 is a candidate gene for
restrictive dermopathy.
*FIELD* AV
.0001
ICHTHYOSIS PREMATURITY SYNDROME
SLC27A4, CYS168TER
In affected members of 18 Scandinavian families segregating ichthyosis
prematurity syndrome (608649), Klar et al. (2009) identified
homozygosity or compound heterozygosity for a 504C-A transversion in
exon 3 of the SLC27A4 gene, resulting in a cys168-to-ter (C168X)
substitution. This finding indicates that C168X is a founder mutation.
Klar et al. (2009) demonstrated absence of full-length SLC27A4 in an IPS
patient homozygous for the mutation. The mutation was not found in 120
healthy control individuals.
.0002
ICHTHYOSIS PREMATURITY SYNDROME
SLC27A4, IVS4AS, G-A, -1
In a North African patient with ichthyosis prematurity syndrome
(608649), daughter to consanguineous parents, Klar et al. (2009)
identified a homozygous acceptor splice site mutation for exon 5
(716-1G-A) in the SLC27A4 gene, predicting a truncated protein.
.0003
ICHTHYOSIS PREMATURITY SYNDROME
SLC27A4, ALA92THR
In affected members of Scandinavian families segregating ichthyosis
prematurity syndrome (608649), Klar et al. (2009) identified compound
heterozygosity for mutations in the SLC27A4 gene: C168X (604194.0001)
and a 274G-A transition in exon 3, resulting in an ala92-to-thr (A92T)
substitution.
.0004
ICHTHYOSIS PREMATURITY SYNDROME
SLC27A4, SER247PRO
In affected members of Scandinavian families segregating ichthyosis
prematurity syndrome (608649), Klar et al. (2009) identified compound
heterozygosity for mutations in the SLC27A4 gene: C168X (604194.0001)
and a 739T-C transition in exon 5, resulting in a ser247-to-pro (S247P)
substitution in the highly conserved AMP-binding domain.
.0005
ICHTHYOSIS PREMATURITY SYNDROME
SLC27A4, GLN300ARG
In affected members of Scandinavian families segregating ichthyosis
prematurity syndrome (608649), Klar et al. (2009) identified compound
heterozygosity for mutations in the SLC27A4 gene: C168X (604194.0001)
and an 899A-G transition in exon 7, resulting in a gln300-to-arg (Q300R)
substitution in the highly conserved AMP-binding domain.
.0006
ICHTHYOSIS PREMATURITY SYNDROME
SLC27A4, IVS7AS, A-G, -2
In affected members of Scandinavian families segregating ichthyosis
prematurity syndrome (608649), Klar et al. (2009) identified compound
heterozygosity for mutations in the SLC27A4 gene: C168X (604194.0001)
and a 988-2A-G splice site mutation.
.0007
ICHTHYOSIS PREMATURITY SYNDROME
SLC27A4, ARG583HIS
In affected members of a Middle Eastern family with ichthyosis
prematurity syndrome (608649), Klar et al. (2009) identified
homozygosity for a 1748G-A transition in exon 12 of the SLC27A4 gene,
resulting in an arg583-to-his (R483H) mutation in the C-terminal domain.
*FIELD* RF
1. Gertow, K.; Bellanda, M.; Eriksson, P.; Boquist, S.; Hamsten, A.;
Sunnerhagen, M.; Fisher, R. M.: Genetic and structural evaluation
of fatty acid transport protein-4 in relation to markers of the insulin
resistance syndrome. J. Clin. Endocr. Metab. 89: 392-399, 2004.
2. Hirsch, D.; Stahl, A.; Lodish, H. F.: A family of fatty acid transporters
conserved from mycobacterium to man. Proc. Nat. Acad. Sci. 95: 8625-8629,
1998.
3. Klar, J.; Schweiger, M.; Zimmerman, R.; Zechner, R.; Li, H.; Torma,
H.; Vahlquist, A.; Bouadjar, B.; Dahl. N.; Fischer, J.: Mutations
in the fatty acid transport protein 4 gene cause the ichthyosis prematurity
syndrome. Am. J. Hum. Genet. 85: 248-253, 2009.
4. Moulson, C. L.; Martin, D. R.; Lugus, J. J.; Schaffer, J. E.; Lind,
A. C.; Miner, J. H.: Cloning of wrinkle-free, a previously uncharacterized
mouse mutation, reveals crucial roles for fatty acid transport protein
4 in skin and hair development. Proc. Nat. Acad. Sci. 100: 5274-5279,
2003.
5. Schaffer, J. E.; Lodish, H. F.: Expression cloning and characterization
of a novel adipocyte long chain fatty acid transport protein. Cell 79:
427-436, 1994.
6. Stahl, A.; Hirsch, D. J.; Gimeno, R. E.; Punreddy, S.; Ge, P.;
Watson, N.; Patel, S.; Kotler, M.; Raimondi, A.; Tartaglia, L. A.;
Lodish, H. F.: Identification of the major intestinal fatty acid
transport protein. Molec. Cell 4: 299-308, 1999.
7. Watkins, P. A.; Maiguel, D.; Jia, Z.; Pevsner, J.: Evidence for
26 distinct acyl-coenzyme A synthetase genes in the human genome. J.
Lipid Res. 48: 2736-2750, 2007.
*FIELD* CN
Patricia A. Hartz - updated: 10/4/2011
Nara Sobreira - updated: 10/7/2009
John A. Phillips, III - updated: 1/2/2007
Victor A. McKusick - updated: 6/13/2003
Carol A. Bocchini - updated: 4/8/2003
Stylianos E. Antonarakis - updated: 10/25/1999
*FIELD* CD
Stylianos E. Antonarakis: 9/28/1999
*FIELD* ED
mgross: 11/30/2011
terry: 10/4/2011
terry: 5/28/2010
carol: 2/16/2010
carol: 10/8/2009
terry: 10/7/2009
alopez: 1/2/2007
alopez: 6/23/2003
terry: 6/13/2003
carol: 4/8/2003
mgross: 10/10/2002
mgross: 10/25/1999
mgross: 9/28/1999
MIM
608649
*RECORD*
*FIELD* NO
608649
*FIELD* TI
#608649 ICHTHYOSIS PREMATURITY SYNDROME; IPS
;;ICHTHYOSIS CONGENITA IV
*FIELD* TX
A number sign (#) is used with this entry because ichthyosis prematurity
read moresyndrome (IPS) is caused by mutation in the FATP4 (SLC27A4; 604194)
gene.
CLINICAL FEATURES
Autosomal recessive congenital ichthyosis is a clinically and
genetically heterogeneous group of inherited keratinization disorders.
The rare subtype ichthyosis prematurity syndrome presents with
complications at mid-trimester of pregnancy leading to prematurity, a
thick caseous and desquamating skin, respiratory complications, and
persistent eosinophilia. Skin features evolve into a flat follicular
hyperkeratosis with atopy (Klar et al., 2004).
POPULATION GENETICS
IPS has a high prevalence in a small geographic region in middle Norway
and adjacent Sweden (see Anton-Lamprecht, 1992 and Klar et al., 2004).
Cases have been reported in other ethnic groups (see, e.g., Niemi et
al., 1993 and Brusasco et al., 1997).
MAPPING
Klar et al. (2004) performed genomewide linkage analysis in 16 families
with ichthyosis prematurity syndrome from Norway and Sweden. Thirteen
families had 1 or 2 affected members or had pairs of sibs with at least
1 affected; 3 families had 1 affected single child. A maximum multipoint
lod score of 3.73 at theta = 0.0 was obtained with the short tandem
repeat D9S778. A 12-cM region was defined by haplotype analysis and
recombinant events at D9S250 and D9S63. This region was further refined
by allelic association to a 1-Mb region at chromosome 9q33.3-q34.13 with
no indication of genetic heterogeneity. Haplotype analysis suggested the
presence of 2 founder mutations.
In 28 affected and 22 healthy sibs from 22 unrelated Norwegian and
Swedish families with ichthyosis prematurity syndrome, 13 of which had
been previously studied by Klar et al. (2004), Melin et al. (2006)
confirmed linkage to chromosome 9q33.3-q34.13 and refined the IPS
haplotype to a 76-kb core region. Sequencing of DNA from 3 patients
revealed no alterations in the exons or flanking intronic sequences of 4
candidate genes, TBC1D13, ENDOG (600440), C9ORF114, and CCBL1 (600547),
and there were no significant differences in transcript levels between
patients and controls for those genes. Based on the average length of
the haplotype in IPS patients, the age of a founder mutation was
calculated to be approximately 1,900 years.
Klar et al. (2009) performed a homozygosity scan on a consanguineous
family of North African origin in which several individuals had
ichthyosis prematurity syndrome. Affected family members were found to
be homozygous for a 76-kb genomic region on chromosome 9p that coincided
with the IPS locus in the Scandinavian families.
PATHOGENESIS
Klar et al. (2009) observed abnormal distribution of lipids between
epidermal layers in ichthyosis prematurity syndrome that is consistent
with the expression pattern of FATP4 in normal epidermis, and suggested
a defect in lipid homeostasis and skin barrier formation in IPS. Klar et
al. (2009) also demonstrated that FATP4 deficiency in human fibroblasts
is associated with reduced VLCFA-CoA synthetase activity and a reduced
incorporation of VLCFA into neutral and polar lipids.
MOLECULAR GENETICS
Klar et al. (2009) performed sequence analysis of the FATP4 gene in a
North African family, a Middle Eastern family, and 18 families of
Scandinavian origin segregating IPS. They identified 7 different
mutations. All affected members of the Scandinavian families were
homozygous or compound heterozygous for a nonsense mutation (C168X;
604194.0001), indicating a founder effect. A splice site mutation
(604194.0002) and a missense mutation (604194.0007) were identified in
homozygosity in affected members of the North African and the Middle
Eastern families, respectively. None of the mutations were found in 120
healthy control individuals.
*FIELD* RF
1. Anton-Lamprecht, I.: The skin.In: Papadimitriou, J. M.; Henderson,
D. W.; Spagnolo, D. V. (eds.): Diagnostic Ultrastructure of Non-neoplastic
Diseases. Edinburgh: Churchill Livingstone 1992. Pp. 459-550.
2. Brusasco, A.; Gelmetti, C.; Tadini, G.; Caputo, R.: Ichthyosis
congenita type IV: a new case resembling diffuse cutaneous mastocytosis. Brit.
J. Derm. 136: 377-379, 1997.
3. Klar, J.; Gedde-Dahl, Jr., T.; Larsson, M.; Pigg, M.; Carlsson,
B.; Tentler, D.; Vahlquist, A.; Dahl, N.: Assignment of the locus
for ichthyosis prematurity syndrome to chromosome 9q33.3-34.13. (Letter) J.
Med. Genet. 41: 208-212, 2004.
4. Klar, J.; Schweiger, M.; Zimmerman, R.; Zechner, R.; Li, H.; Torma,
H.; Vahlquist, A.; Bouadjar, B.; Dahl. N.; Fischer, J.: Mutations
in the fatty acid transport protein 4 gene cause the ichthyosis prematurity
syndrome. Am. J. Hum. Genet. 85: 248-253, 2009.
5. Melin, M.; Klar, J.; Gedde-Dahl, T., Jr.; Fredriksson, R.; Hausser,
I.; Brandrup, F.; Bygum, A.; Vahlquist, A.; Hellstrom Pigg, M.; Dahl.
N.: a founder mutation for ichthyosis prematurity syndrome restricted
to 76 kb by haplotype association. J. Hum. Genet. 51: 864-871, 2006.
6. Niemi, K.-M.; Kuokkanen, K.; Kanerva, L.; Ignatius, J.: Recessive
ichthyosis congenita type IV. Am. J. Derm. 15: 224-228, 1993.
*FIELD* CN
Nara Sobreira - updated: 10/7/2009
Marla J. F. O'Neill - updated: 1/2/2007
*FIELD* CD
Natalie E. Krasikov: 5/11/2004
*FIELD* ED
carol: 10/08/2009
terry: 10/7/2009
wwang: 1/2/2007
terry: 3/22/2006
carol: 5/11/2004
*RECORD*
*FIELD* NO
608649
*FIELD* TI
#608649 ICHTHYOSIS PREMATURITY SYNDROME; IPS
;;ICHTHYOSIS CONGENITA IV
*FIELD* TX
A number sign (#) is used with this entry because ichthyosis prematurity
read moresyndrome (IPS) is caused by mutation in the FATP4 (SLC27A4; 604194)
gene.
CLINICAL FEATURES
Autosomal recessive congenital ichthyosis is a clinically and
genetically heterogeneous group of inherited keratinization disorders.
The rare subtype ichthyosis prematurity syndrome presents with
complications at mid-trimester of pregnancy leading to prematurity, a
thick caseous and desquamating skin, respiratory complications, and
persistent eosinophilia. Skin features evolve into a flat follicular
hyperkeratosis with atopy (Klar et al., 2004).
POPULATION GENETICS
IPS has a high prevalence in a small geographic region in middle Norway
and adjacent Sweden (see Anton-Lamprecht, 1992 and Klar et al., 2004).
Cases have been reported in other ethnic groups (see, e.g., Niemi et
al., 1993 and Brusasco et al., 1997).
MAPPING
Klar et al. (2004) performed genomewide linkage analysis in 16 families
with ichthyosis prematurity syndrome from Norway and Sweden. Thirteen
families had 1 or 2 affected members or had pairs of sibs with at least
1 affected; 3 families had 1 affected single child. A maximum multipoint
lod score of 3.73 at theta = 0.0 was obtained with the short tandem
repeat D9S778. A 12-cM region was defined by haplotype analysis and
recombinant events at D9S250 and D9S63. This region was further refined
by allelic association to a 1-Mb region at chromosome 9q33.3-q34.13 with
no indication of genetic heterogeneity. Haplotype analysis suggested the
presence of 2 founder mutations.
In 28 affected and 22 healthy sibs from 22 unrelated Norwegian and
Swedish families with ichthyosis prematurity syndrome, 13 of which had
been previously studied by Klar et al. (2004), Melin et al. (2006)
confirmed linkage to chromosome 9q33.3-q34.13 and refined the IPS
haplotype to a 76-kb core region. Sequencing of DNA from 3 patients
revealed no alterations in the exons or flanking intronic sequences of 4
candidate genes, TBC1D13, ENDOG (600440), C9ORF114, and CCBL1 (600547),
and there were no significant differences in transcript levels between
patients and controls for those genes. Based on the average length of
the haplotype in IPS patients, the age of a founder mutation was
calculated to be approximately 1,900 years.
Klar et al. (2009) performed a homozygosity scan on a consanguineous
family of North African origin in which several individuals had
ichthyosis prematurity syndrome. Affected family members were found to
be homozygous for a 76-kb genomic region on chromosome 9p that coincided
with the IPS locus in the Scandinavian families.
PATHOGENESIS
Klar et al. (2009) observed abnormal distribution of lipids between
epidermal layers in ichthyosis prematurity syndrome that is consistent
with the expression pattern of FATP4 in normal epidermis, and suggested
a defect in lipid homeostasis and skin barrier formation in IPS. Klar et
al. (2009) also demonstrated that FATP4 deficiency in human fibroblasts
is associated with reduced VLCFA-CoA synthetase activity and a reduced
incorporation of VLCFA into neutral and polar lipids.
MOLECULAR GENETICS
Klar et al. (2009) performed sequence analysis of the FATP4 gene in a
North African family, a Middle Eastern family, and 18 families of
Scandinavian origin segregating IPS. They identified 7 different
mutations. All affected members of the Scandinavian families were
homozygous or compound heterozygous for a nonsense mutation (C168X;
604194.0001), indicating a founder effect. A splice site mutation
(604194.0002) and a missense mutation (604194.0007) were identified in
homozygosity in affected members of the North African and the Middle
Eastern families, respectively. None of the mutations were found in 120
healthy control individuals.
*FIELD* RF
1. Anton-Lamprecht, I.: The skin.In: Papadimitriou, J. M.; Henderson,
D. W.; Spagnolo, D. V. (eds.): Diagnostic Ultrastructure of Non-neoplastic
Diseases. Edinburgh: Churchill Livingstone 1992. Pp. 459-550.
2. Brusasco, A.; Gelmetti, C.; Tadini, G.; Caputo, R.: Ichthyosis
congenita type IV: a new case resembling diffuse cutaneous mastocytosis. Brit.
J. Derm. 136: 377-379, 1997.
3. Klar, J.; Gedde-Dahl, Jr., T.; Larsson, M.; Pigg, M.; Carlsson,
B.; Tentler, D.; Vahlquist, A.; Dahl, N.: Assignment of the locus
for ichthyosis prematurity syndrome to chromosome 9q33.3-34.13. (Letter) J.
Med. Genet. 41: 208-212, 2004.
4. Klar, J.; Schweiger, M.; Zimmerman, R.; Zechner, R.; Li, H.; Torma,
H.; Vahlquist, A.; Bouadjar, B.; Dahl. N.; Fischer, J.: Mutations
in the fatty acid transport protein 4 gene cause the ichthyosis prematurity
syndrome. Am. J. Hum. Genet. 85: 248-253, 2009.
5. Melin, M.; Klar, J.; Gedde-Dahl, T., Jr.; Fredriksson, R.; Hausser,
I.; Brandrup, F.; Bygum, A.; Vahlquist, A.; Hellstrom Pigg, M.; Dahl.
N.: a founder mutation for ichthyosis prematurity syndrome restricted
to 76 kb by haplotype association. J. Hum. Genet. 51: 864-871, 2006.
6. Niemi, K.-M.; Kuokkanen, K.; Kanerva, L.; Ignatius, J.: Recessive
ichthyosis congenita type IV. Am. J. Derm. 15: 224-228, 1993.
*FIELD* CN
Nara Sobreira - updated: 10/7/2009
Marla J. F. O'Neill - updated: 1/2/2007
*FIELD* CD
Natalie E. Krasikov: 5/11/2004
*FIELD* ED
carol: 10/08/2009
terry: 10/7/2009
wwang: 1/2/2007
terry: 3/22/2006
carol: 5/11/2004