FAT4

Protein identityUniProt · HPA

UniProt accession

Q6V0I7

Gene

FAT4

Ensembl

ENSG00000196159

Chromosome

4

Canonical length

4981 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Predicted membrane proteins

Subcellular location

Cytosol

OverviewNCBI Gene

The protein encoded by this gene is a member of the protocadherin family. This gene may play a role in regulating planar cell polarity (PCP). Studies in mice suggest that loss of PCP signaling may cause cystic kidney disease, and mutations in this gene have been associated with Van Maldergem Syndrome 2. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Mar 2014]

Canonical amino-acid sequenceUniProt

4981 residues, UniProt reviewed canonical sequence.

>Q6V0I7|FAT4
     1  MDLAPDRATG RPWLPLHTLS VSQLLRVFWL LSLLPGQAWV HGAEPRQVFQ VLEEQPPGTL
    61  VGTIQTRPGF TYRLSESHAL FAINSSTGAL YTTSTIDRES LPSDVINLVV LSSAPTYPTE
   121  VRVLVRDLND NAPVFPDPSI VVTFKEDSSS GRQVILDTAT DSDIGSNGVD HRSYRIIRGN
   181  EAGRFRLDIT LNPSGEGAFL HLVSKGGLDR EVTPQYQLLV EVEDKGEPKR RGYLQVNVTV
   241  QDINDNPPVF GSSHYQAGVP EDAVVGSSVL QVAAADADEG TNADIRYRLQ DEGTPFQMDP
   301  ETGLITVREP LDFEARRQYS LTVQAMDRGV PSLTGRAEAL IQLLDVNDND PVVKFRYFPA
   361  TSRYASVDEN AQVGTVVALL TVTDADSPAA NGNISVQILG GNEQRHFEVQ SSKVPNLSLI
   421  KVASALDRER IPSYNLTVSV SDNYGAPPGA AVQARSSVAS LVIFVNDIND HPPVFSQQVY
   481  RVNLSEEAPP GSYVSGISAT DGDSGLNANL RYSIVSGNGL GWFHISEHSG LVTTGSSGGL
   541  DRELASQIVL NISARDQGVH PKVSYAQLVV TLLDVNDEKP VFSQPEGYDV SVVENAPTGT
   601  ELLMLRATDG DLGDNGTVRF SLQEAETDRR SFRLDPVSGR LSTISSLDRE EQAFYSLLVL
   661  ATDLGSPPQS SMARINVSLL DINDNSPVFY PVQYFAHIKE NEPGGSYITT VSATDPDLGT
   721  NGTVKYSISA GDRSRFQVNA QSGVISTRMA LDREEKTAYQ LQIVATDGGN LQSPNQAIVT
   781  ITVLDTQDNP PVFSQVAYSF VVFENVALGY HVGSVSASTM DLNSNISYLI TTGDQKGMFA
   841  INQVTGQLTT ANVIDREEQS FYQLKVVASG GTVTGDTMVN ITVKDLNDNS PHFLQAIESV
   901  NVVENWQAGH SIFQAKAVDP DEGVNGMVLY SLKQNPKNLF AINEKNGTIS LLGPLDVHAG
   961  SYQIEILASD MGVPQLSSSV ILTVYVHDVN DNSPVFDQLS YEVTLSESEP VNSRFFKVQA
  1021  SDKDSGANGE IAYTIAEGNT GDAFGIFPDG QLYIKSELDR ELQDRYVLMV VASDRAVEPL
  1081  SATVNVTVIL EDVNDNRPLF NSTNYTFYFE EEQRAGSFVG KVSAVDKDFG PNGEVRYSFE
  1141  MVQPDFELHA ISGEITNTHQ FDRESLMRRR GTAVFSFTVI ATDQGIPQPL KDQATVHVYM
  1201  KDINDNAPKF LKDFYQATIS ESAANLTQVL RVSASDVDEG NNGLIHYSII KGNEERQFAI
  1261  DSTSGQVTLI GKLDYEATPA YSLVIQAVDS GTIPLNSTCT LNIDILDEND NTPSFPKSTL
  1321  FVDVLENMRI GELVSSVTAT DSDSGDNADL YYSITGTNNH GTFSISPNTG SIFLAKKLDF
  1381  ETQSLYKLNI TAKDQGRPPR SSTMSVVIHV RDFNDNPPSF PPGDIFKSIV ENIPIGTSVI
  1441  SVTAHDPDAD INGQLSYTII QQMPRGNHFT IDEVKGTIYT NAEIDREFAN LFELTVKAND
  1501  QAVPIETRRY ALKNVTILVT DLNDNVPMFI SQNALAADPS AVIGSVLTTI MAADPDEGAN
  1561  GEIEYEIING DTDTFIVDRY SGDLRVASAL VPSQLIYNLI VSATDLGPER RKSTTELTII
  1621  LQGLDGPVFT QPKYITILKE GEPIGTNVIS IEAASPRGSE APVEYYIVSV RCEEKTVGRL
  1681  FTIGRHTGII QTAAILDREQ GACLYLVDVY AIEKSTAFPR TQRAEVEITL QDINDNPPVF
  1741  PTDMLDLTVE ENIGDGSKIM QLTAMDADEG ANALVTYTII SGADDSFRID PESGDLIATR
  1801  RLDRERRSKY SLLVRADDGL QSSDMRINIT VSDVNDHTPK FSRPVYSFDI PEDTIPGSLV
  1861  AAILATDDDS GVNGEITYIV NEDDEDGIFF LNPITGVFNL TRLLDYEVQQ YYILTVRAED
  1921  GGGQFTTIRV YFNILDVNDN PPIFSLNSYS TSLMENLPVG STVLVFNVTD ADDGINSQLT
  1981  YSIASGDSLG QFTVDKNGVL KVLKALDRES QSFYNLVVQV HDLPQIPASR FTSTAQVSII
  2041  LLDVNDNPPT FLSPKLTYIP ENTPIDTVVF KAQATDPDSG PNSYIEYTLL NPLGNKFSIG
  2101  TIDGEVRLTG ELDREEVSNY TLTVVATDKG QPSLSSSTEV VVMVLDINDN NPIFAQALYK
  2161  VEINENTLTG TDIIQVFAAD GDEGTNGQVR YGIVNGNTNQ EFRIDSVTGA ITVAKPLDRE
  2221  KTPTYHLTVQ ATDRGSTPRT DTSTVSIVLL DINDFVPVFE LSPYSVNVPE NLGTLPRTIL
  2281  QVVARDDDRG SNSKLSYVLF GGNEDNAFTL SASGELGVTQ SLDRETKERF VLMITATDSG
  2341  SPALTGTGTI NVIVDDVNDN VPTFASKAYF TTIPEDAPTG TDVLLVNASD ADASKNAVIR
  2401  IIGGNSQFTI NPSTGQIITS ALLDRETKDN YTLVVVCSDA GSPEPLSSST SVLVTVTDVN
  2461  DNPPRFQHHP YVTHIPSPTL PGSFVFAVTV TDADIGPNSE LHYSLSGRNS EKFHIDPLRG
  2521  AIMAAGPLNG ASEVTFSVHV KDGGSFPKTD STTVTVRFVN KADFPKVRAK EQTFMFPENQ
  2581  PVSSLVTTIT GSSLRGEPMS YYIASGNLGN TFQIDQLTGQ VSISQPLDFE KIQKYVVWIE
  2641  ARDGGFPPFS SYEKLDITVL DVNDNAPIFK EDPFISEILE NLSPRKILTV SAMDKDSGPN
  2701  GQLDYEIVNG NMENSFSINH ATGEIRSVRP LDREKVSHYV LTIKSSDKGS PSQSTSVKVM
  2761  INILDENDNA PRFSQIFSAH VPENSPLGYT VTRVTTSDED IGINAISRYS IMDASLPFTI
  2821  NPSTGDIVIS RPLNREDTDR YRIRVSAHDS GWTVSTDVTI FVTDINDNAP RFSRTSYYLD
  2881  CPELTEIGSK VTQVFATDPD EGSNGQVFYF IKSQSEYFRI NATTGEIFNK QILKYQNVTG
  2941  FSNVNINRHS FIVTSSDRGK PSLISETTVT INIVDSNDNA PQFLKSKYFT PVTKNVKVGT
  3001  KLIRVTAIDD KDFGLNSEVE YFISNDNHLG KFKLDNDTGW ISVASSLISD LNQNFFITVT
  3061  AKDKGNPPLS SQATVHITVT EENYHTPEFS QSHMSATIPE SHSIGSIVRT VSARDRDAAM
  3121  NGLIKYSISS GNEEGIFAIN SSTGILTLAK ALDYELCQKH EMTISAIDGG WVARTGYCSV
  3181  TVNVIDVNDN SPVFLSDDYF PTVLENAPSG TTVIHLNATD ADSGTNAVIA YTVQSSDSDL
  3241  FVIDPNTGVI TTQGFLDFET KQSYHLTVKA FNVPDEERCS FATVNIQLKG TNEYVPRFVS
  3301  KLYYFEISEA APKGTIVGEV FASDRDLGTD GEVHYLIFGN SRKKGFQINK KTGQIYVSGI
  3361  LDREKEERVS LKVLAKNFGS IRGADIDEVT VNVTVLDAND PPIFTLNIYS VQISEGVPIG
  3421  THVTFVSAFD SDSIPSWSRF SYFIGSGNEN GAFSINPQTG QITVTAELDR ETLPIYNLSV
  3481  LAVDSGTPSA TGSASLLVTL EDINDNGPML TVSEGEVMEN KRPGTLVMTL QSTDPDLPPN
  3541  QGPFTYYLLS TGPATSYFSL STAGVLSTTR EIDREQIADF YLSVVTKDSG VPQMSSTGTV
  3601  HITVIDQNDN PSQSRTVEIF VNYYGNLFPG GILGSVKPQD PDVLDSFHCS LTSGVTSLFS
  3661  IPGGTCDLNS QPRSTDGTFD LTVLSNDGVH STVTSNIRVF FAGFSNATVD NSILLRLGVP
  3721  TVKDFLTNHY LHFLRIASSQ LTGLGTAVQL YSAYEENNRT FLLAAVKRNH NQYVNPSGVA
  3781  TFFESIKEIL LRQSGVKVES VDHDSCVHGP CQNGGSCLRR LAVSSVLKSR ESLPVIIVAN
  3841  EPLQPFLCKC LPGYAGSWCE IDIDECLPSP CHSGGTCHNL VGGFSCSCPD GFTGRACERD
  3901  INECLQSPCK NGAICQNFPG SFNCVCKTGY TGKMCESSVN YCECNPCFNG GSCQSGVDSY
  3961  YCHCPFGVFG KHCELNSYGF EELSYMEFPS LDPNNNYIYV KFATIKSHAL LLYNYDNQTG
  4021  DRAEFLALEI AEERLRFSYN LGSGTYKLTT MKKVSDGHFH TVIARRAGMA ASLTVDSCSE
  4081  NQEPGYCTVS NVAVSDDWTL DVQPNRVTVG GIRSLEPILQ RRGHVESHDF VGCIMEFAVN
  4141  GRPLEPSQAL AAQGILDQCP RLEGACTRSP CQHGGTCMDY WSWQQCHCKE GLTGKYCEKS
  4201  VTPDTALSLE GKGRLDYHMS QNEKREYLLR QSLRGAMLEP FGVNSLEVKF RTRSENGVLI
  4261  HIQESSNYTT VKIKNGKVYF TSDAGIAGKV ERNIPEVYVA DGHWHTFLIG KNGTATVLSV
  4321  DRIYNRDIIH PTQDFGGLDV LTISLGGIPP NQAHRDAQTA GFDGCIASMW YGGESLPFSG
  4381  KHSLASISKT DPSVKIGCRG PNICASNPCW GDLLCINQWY AYRCVPPGDC ASHPCQNGGS
  4441  CEPGLHSGFT CSCPDSHTGR TCEMVVACLG VLCPQGKVCK AGSPAGHVCV LSQGPEEISL
  4501  PLWAVPAIVG SCATVLALLV LSLILCNQCR GKKAKNPKEE KKPKEKKKKG SENVAFDDPD
  4561  NIPPYGDDMT VRKQPEGNPK PDIIERENPY LIYDETDIPH NSETIPSAPL ASPEQEIEHY
  4621  DIDNASSIAP SDADIIQHYK QFRSHTPKFS IQRHSPLGFA RQSPMPLGAS SLTYQPSYGQ
  4681  GLRTSSLSHS ACPTPNPLSR HSPAPFSKSS TFYRNSPARE LHLPIRDGNT LEMHGDTCQP
  4741  GIFNYATRLG RRSKSPQAMA SHGSRPGSRL KQPIGQIPLE SSPPVGLSIE EVERLNTPRP
  4801  RNPSICSADH GRSSSEEDCR RPLSRTRNPA DGIPAPESSS DSDSHESFTC SEMEYDREKP
  4861  MVYTSRMPKL SQVNESDADD EDNYGARLKP RRYHGRRAEG GPVGTQAAAP GTADNTLPMK
  4921  LGQQAGTFNW DNLLNWGPGF GHYVDVFKDL ASLPEKAAAN EEGKAGTTKP VPKDGEAEQY
  4981  V

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FAT4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0

Highest tissue expression

9.4 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FAT4.

Disease | AllUniProt

Conditions FAT4 is implicated in, by any mechanism.

• Van Maldergem syndrome 2 (VMLDS2) MIM:615546
• Hennekam lymphangiectasia-lymphedema syndrome 2 (HKLLS2) MIM:616006

Disease | GeneticClinVar

67 pathogenic / likely-pathogenic of 3,570 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Van Maldergem syndrome 2
• Hennekam lymphangiectasia-lymphedema syndrome 2
• FAT4-related disorder
• Van Maldergem syndrome
• Autosomal recessive FAT4-related disorders

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.18

gnomAD pLI

1

gnomAD missense Z

0.62

DepMap mean gene effect

-0.07

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• axonogenesis
• cell-cell adhesion mediated by cadherin
• cerebral cortex development
• epithelial cell differentiation
• heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
• hippo signaling
• homophilic cell adhesion via plasma membrane adhesion molecules
• neurogenesis

Molecular functions

• calcium ion binding

Cellular components

• adherens junction
• extracellular exosome
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• EGF-type aspartate/asparagine hydroxylation site
• EGF-like domain
• Laminin G domain
• EGF-like calcium-binding domain
• Cadherin-like
• Growth factor receptor cysteine-rich domain superfamily
• EGF-like, conserved site
• Concanavalin A-like lectin/glucanase domain superfamily
• Cadherin-like superfamily
• EGF-like calcium-binding, conserved site
• Cadherin conserved site
• Cadherin
• NOTCH1, EGF-like calcium-binding domain
• EGF-like domain
• Cadherin domain
• Laminin G domain
• Calcium-binding EGF domain
• Human growth factor-like EGF
• FAT4-like, N-terminal cadherin-like domain

KeywordsUniProt

• Calcium
• Cell adhesion
• Deafness
• Disulfide bond
• EGF-like domain
• Glycoprotein
• Intellectual disability
• Membrane
• Phosphoprotein
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of FAT4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MPDZ