Seroatlas · Human Serome Atlas

WDFY3

WD repeat and FYVE domain-containing protein 3

Also known as: ALFY, KIAA0993, WDFY3_HUMAN, ZFYVE25

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q8IZQ1
Gene: WDFY3
Ensembl: ENSG00000163625
Chromosome: 4
Canonical length: 3526 aa
Protein class: Disease related genes, Human disease related genes, Predicted intracellular proteins
Subcellular location: Nucleoli,Plasma membrane,Cytosol

OverviewNCBI Gene

This gene encodes a phosphatidylinositol 3-phosphate-binding protein that functions as a master conductor for aggregate clearance by autophagy. This protein shuttles from the nuclear membrane to colocalize with aggregated proteins, where it complexes with other autophagic components to achieve macroautophagy-mediated clearance of these aggregated proteins. However, it is not necessary for starvation-induced macroautophagy. [provided by RefSeq, May 2010]

Canonical amino-acid sequenceUniProt

3526 residues, UniProt reviewed canonical sequence.

>Q8IZQ1|WDFY3
     1  MNMVKRIMGR PRQEECSPQD NALGLMHLRR LFTELCHPPR HMTQKEQEEK LYMMLPVFNR
    61  VFGNAPPNTM TEKFSDLLQF TTQVSRLMVT EIRRRASNKS TEAASRAIVQ FLEINQSEEA
   121  SRGWMLLTTI NLLASSGQKT VDCMTTMSVP STLVKCLYLF FDLPHVPEAV GGAQNELPLA
   181  ERRGLLQKVF VQILVKLCSF VSPAEELAQK DDLQLLFSAI TSWCPPYNLP WRKSAGEVLM
   241  TISRHGLSVN VVKYIHEKEC LSTCVQNMQQ SDDLSPLEIV EMFAGLSCFL KDSSDVSQTL
   301  LDDFRIWQGY NFLCDLLLRL EQAKEAESKD ALKDLVNLIT SLTTYGVSEL KPAGITTGAP
   361  FLLPGFAVPQ PAGKGHSVRN VQAFAVLQNA FLKAKTSFLA QIILDAITNI YMADNANYFI
   421  LESQHTLSQF AEKISKLPEV QNKYFEMLEF VVFSLNYIPC KELISVSILL KSSSSYHCSI
   481  IAMKTLLKFT RHDYIFKDVF REVGLLEVMV NLLHKYAALL KDPTQALNEQ GDSRNNSSVE
   541  DQKHLALLVM ETLTVLLQGS NTNAGIFREF GGARCAHNIV KYPQCRQHAL MTIQQLVLSP
   601  NGDDDMGTLL GLMHSAPPTE LQLKTDILRA LLSVLRESHR SRTVFRKVGG FVYITSLLVA
   661  MERSLSCPPK NGWEKVNQNQ VFELLHTVFC TLTAAMRYEP ANSHFFKTEI QYEKLADAVR
   721  FLGCFSDLRK ISAMNVFPSN TQPFQRLLEE DVISIESVSP TLRHCSKLFI YLYKVATDSF
   781  DSRAEQIPPC LTSESSLPSP WGTPALSRKR HAYHSVSTPP VYPPKNVADL KLHVTTSSLQ
   841  SSDAVIIHPG AMLAMLDLLA SVGSVTQPEH ALDLQLAVAN ILQSLVHTER NQQVMCEAGL
   901  HARLLQRCSA ALADEDHSLH PPLQRMFERL ASQALEPMVL REFLRLASPL NCGAWDKKLL
   961  KQYRVHKPSS LSYEPEMRSS MITSLEGLGT DNVFSLHEDN HYRISKSLVK SAEGSTVPLT
  1021  RVKCLVSMTT PHDIRLHGSS VTPAFVEFDT SLEGFGCLFL PSLAPHNAPT NNTVTTGLID
  1081  GAVVSGIGSG ERFFPPPSGL SYSSWFCIEH FSSPPNNHPV RLLTVVRRAN SSEQHYVCLA
  1141  IVLSAKDRSL IVSTKEELLQ NYVDDFSEES SFYEILPCCA RFRCGELIIE GQWHHLVLVM
  1201  SKGMLKNSTA ALYIDGQLVN TVKLHYVHST PGGSGSANPP VVSTVYAYIG TPPAQRQIAS
  1261  LVWRLGPTHF LEEVLPSSNV TTIYELGPNY VGSFQAVCMP CKDAKSEGVV PSPVSLVPEE
  1321  KVSFGLYALS VSSLTVARIR KVYNKLDSKA IAKQLGISSH ENATPVKLIH NSAGHLNGSA
  1381  RTIGAALIGY LGVRTFVPKP VATTLQYVGG AAAILGLVAM ASDVEGLYAA VKALVCVVKS
  1441  NPLASKEMER IKGYQLLAML LKKKRSLLNS HILHLTFSLV GTVDSGHETS IIPNSTAFQD
  1501  LLCDFEVWLH APYELHLSLF EHFIELLTES SEASKNAKLM REFQLIPKLL LTLRDMSLSQ
  1561  PTIAAISNVL SFLLQGFPSS NDLLRFGQFI SSTLPTFAVC EKFVVMEINN EEKLDTGTEE
  1621  EFGGLVSANL ILLRNRLLDI LLKLIYTSKE KTSINLQACE ELVKTLGFDW IMMFMEEHLH
  1681  STTVTAAMRI LVVLLSNQSI LIKFKEGLSG GGWLEQTDSV LTNKIGTVLG FNVGRSAGGR
  1741  STVREINRDA CHFPGFPVLQ SFLPKHTNVP ALYFLLMALF LQQPVSELPE NLQVSVPVIS
  1801  CRSKQGCQFD LDSIWTFIFG VPASSGTVVS SIHNVCTEAV FLLLGMLRSM LTSPWQSEEE
  1861  GSWLREYPVT LMQFFRYLYH NVPDLASMWM SPDFLCALAA TVFPFNIRPY SEMVTDLDDE
  1921  VGSPAEEFKA FAADTGMNRS QSEYCNVGTK TYLTNHPAKK FVFDFMRVLI IDNLCLTPAS
  1981  KQTPLIDLLL EASPERSTRT QQKEFQTYIL DSVMDHLLAA DVLLGEDASL PITSGGSYQV
  2041  LVNNVFYFTQ RVVDKLWQGM FNKESKLLID FIIQLIAQSK RRSQGLSLDA VYHCLNRTIL
  2101  YQFSRAHKTV PQQVALLDSL RVLTVNRNLI LGPGNHDQEF ISCLAHCLIN LHVGSNVDGF
  2161  GLEAEARMTT WHIMIPSDIE PDGSYSQDIS EGRQLLIKAV NRVWTELIHS KKQVLEELFK
  2221  VTLPVNERGH VDIATARPLI EEAALKCWQN HLAHEKKCIS RGEALAPTTQ SKLSRVSSGF
  2281  GLSKLTGSRR NRKESGLNKH SLSTQEISQW MFTHIAVVRD LVDTQYKEYQ ERQQNALKYV
  2341  TEEWCQIECE LLRERGLWGP PIGSHLDKWM LEMTEGPCRM RKKMVRNDMF YNHYPYVPET
  2401  EQETNVASEI PSKQPETPDD IPQKKPARYR RAVSYDSKEY YMRLASGNPA IVQDAIVESS
  2461  EGEAAQQEPE HGEDTIAKVK GLVKPPLKRS RSAPDGGDEE NQEQLQDQIA EGSSIEEEEK
  2521  TDNATLLRLL EEGEKIQHMY RCARVQGLDT SEGLLLFGKE HFYVIDGFTM TATREIRDIE
  2581  TLPPNMHEPI IPRGARQGPS QLKRTCSIFA YEDIKEVHKR RYLLQPIAVE VFSGDGRNYL
  2641  LAFQKGIRNK VYQRFLAVVP SLTDSSESVS GQRPNTSVEQ GSGLLSTLVG EKSVTQRWER
  2701  GEISNFQYLM HLNTLAGRSY NDLMQYPVFP WILADYDSEE VDLTNPKTFR NLAKPMGAQT
  2761  DERLAQYKKR YKDWEDPNGE TPAYHYGTHY SSAMIVASYL VRMEPFTQIF LRLQGGHFDL
  2821  ADRMFHSVRE AWYSASKHNM ADVKELIPEF FYLPEFLFNS NNFDLGCKQN GTKLGDVILP
  2881  PWAKGDPREF IRVHREALEC DYVSAHLHEW IDLIFGYKQQ GPAAVEAVNV FHHLFYEGQV
  2941  DIYNINDPLK ETATIGFINN FGQIPKQLFK KPHPPKRVRS RLNGDNAGIS VLPGSTSDKI
  3001  FFHHLDNLRP SLTPVKELKE PVGQIVCTDK GILAVEQNKV LIPPTWNKTF AWGYADLSCR
  3061  LGTYESDKAM TVYECLSEWG QILCAICPNP KLVITGGTST VVCVWEMGTS KEKAKTVTLK
  3121  QALLGHTDTV TCATASLAYH IIVSGSRDRT CIIWDLNKLS FLTQLRGHRA PVSALCINEL
  3181  TGDIVSCAGT YIHVWSINGN PIVSVNTFTG RSQQIICCCM SEMNEWDTQN VIVTGHSDGV
  3241  VRFWRMEFLQ VPETPAPEPA EVLEMQEDCP EAQIGQEAQD EDSSDSEADE QSISQDPKDT
  3301  PSQPSSTSHR PRAASCRATA AWCTDSGSDD SRRWSDQLSL DEKDGFIFVN YSEGQTRAHL
  3361  QGPLSHPHPN PIEVRNYSRL KPGYRWERQL VFRSKLTMHT AFDRKDNAHP AEVTALGISK
  3421  DHSRILVGDS RGRVFSWSVS DQPGRSAADH WVKDEGGDSC SGCSVRFSLT ERRHHCRNCG
  3481  QLFCQKCSRF QSEIKRLKIS SPVRVCQNCY YNLQHERGSE DGPRNC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against WDFY3 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: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0
Highest tissue expression: 19 nTPM

Expression across tissuesHPA

Tissue

retina: 19 nTPM
spinal cord: 15 nTPM
kidney: 14 nTPM
parathyroid gland: 12 nTPM
bone marrow: 12 nTPM
cerebellum: 11 nTPM

Single-cell type

neutrophils: 3,005 nCPM
neutrophil progenitors: 879 nCPM
ependymal cells: 659 nCPM
proximal tubule cells: 628 nCPM
sertoli cells: 526 nCPM
lactotrophs: 514 nCPM

Immune cell

neutrophil: 1.4 nTPM
classical monocyte: 0.2 nTPM
intermediate monocyte: 0.2 nTPM
myeloid DC: 0.1 nTPM
non-classical monocyte: 0.1 nTPM
total PBMC: 0.1 nTPM

Brain region

white matter: 141 nTPM
medulla oblongata: 123 nTPM
basal ganglia: 121 nTPM
midbrain: 120 nTPM
cerebellum: 112 nTPM
thalamus: 110 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about WDFY3.

Disease | AllUniProt

Conditions WDFY3 is implicated in, by any mechanism.

Microcephaly 18, primary, autosomal dominant (MCPH18) MIM:617520

Disease | GeneticClinVar

91 pathogenic / likely-pathogenic of 1,083 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Microcephaly 18, primary, autosomal dominant
Neurodevelopmental delay
Inborn genetic diseases
Autosomal dominant WDFY3-related disorders
Neurodevelopmental disorder

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): 0.07
gnomAD pLI: 1
gnomAD missense Z: 5.82
DepMap mean gene effect: -0.09
DepMap dependency class: selective

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

aggrephagy

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of WDFY3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads WDFY3 as an antibody target. Whether an autoantibody or antibody against WDFY3 could matter depends on whether native WDFY3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

WDFY3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label WDFY3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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