Seroatlas · Human Serome Atlas

ZFHX3

Zinc finger homeobox protein 3

Also known as: ATBF1, C16orf47, FLJ26184, ZFHX3_HUMAN, ZNF927

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

Protein identityUniProt · HPA

UniProt accession: Q15911
Gene: ZFHX3
Ensembl: ENSG00000140836
Chromosome: 16
Canonical length: 3703 aa
Protein class: Cancer-related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Transcription factors
Subcellular location: Nucleoplasm

OverviewNCBI Gene

This gene encodes a transcription factor with multiple homeodomains and zinc finger motifs, and regulates myogenic and neuronal differentiation. The encoded protein suppresses expression of the alpha-fetoprotein gene by binding to an AT-rich enhancer motif. The protein has also been shown to negatively regulate c-Myb, and transactivate the cell cycle inhibitor cyclin-dependent kinase inhibitor 1A (also known as p21CIP1). This gene is reported to function as a tumor suppressor in several cancers, and sequence variants of this gene are also associated with atrial fibrillation. Multiple transcript variants expressed from alternate promoters and encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

Canonical amino-acid sequenceUniProt

3703 residues, UniProt reviewed canonical sequence.

>Q15911|ZFHX3
     1  MEGCDSPVVS GKDNGCGIPQ HQQWTELNST HLPDKPSSME QSTGESHGPL DSLRAPFNER
    61  LAESTASAGP PSEPASKEVT CNECSASFAS LQTYMEHHCP SARPPPPLRE ESASDTGEEG
   121  DEESDVENLA GEIVYQPDGS AYIVESLSQL TQGGGACGSG SGSGPLPSLF LNSLPGAGGK
   181  QGDPSCAAPV YPQIINTFHI ASSFGKWFEG PDQAFPNTSA LAGLSPVLHS FRVFDVRHKS
   241  NKDYLNSDGS AKSSCVSKDV PNNVDLSKFD GFVLYGKRKP ILMCFLCKLS FGYVRSFVTH
   301  AVHDHRMTLS EDERKILSNK NISAIIQGIG KDKEPLVSFL EPKNKNFQHP LVSTANLIGP
   361  GHSFYGKFSG IRMEGEEALP AGSAAGPEQP QAGLLTPSTL LNLGGLTSSV LKTPITSVPL
   421  GPLASSPTKS SEGKDSGAAE GEKQEVGDGD CFSEKVEPAE EEAEEEEEEE EAEEEEEEEE
   481  EEEEEEEDEG CKGLFPSELD EELEDRPHEE PGAAAGSSSK KDLALSNQSI SNSPLMPNVL
   541  QTLSRGTAST SSNSASSFVV FDGANRRNRL SFNSEGVRAN VAEGGRRLDF ADESANKDNA
   601  TAPEPNESTE GDDGGFVPHH QHAGSLCELG VGECPSGSGV ECPKCDTVLG SSRSLGGHMT
   661  MMHSRNSCKT LKCPKCNWHY KYQQTLEAHM KEKHPEPGGS CVYCKSGQPH PRLARGESYT
   721  CGYKPFRCEV CNYSTTTKGN LSIHMQSDKH LNNMQNLQNG GGEQVFSHTA GAAAAAVAAA
   781  AAAANISSSC GAPSPTKPKT KPTWRCEVCD YETNVARNLR IHMTSEKHMH NMMLLQQNMT
   841  QIQHNRHLGL GSLPSPAEAE LYQYYLAQNM NLPNLKMDSA ASDAQFMMSG FQLDPAGPMA
   901  AMTPALVGGE IPLDMRLGGG QLVSEELMNL GESFIQTNDP SLKLFQCAVC NKFTTDNLDM
   961  LGLHMNVERS LSEDEWKAVM GDSYQCKLCR YNTQLKANFQ LHCKTDKHVQ KYQLVAHIKE
  1021  GGKANEWRLK CVAIGNPVHL KCNACDYYTN SLEKLRLHTV NSRHEASLKL YKHLQQHESG
  1081  VEGESCYYHC VLCNYSTKAK LNLIQHVRSM KHQRSESLRK LQRLQKGLPE EDEDLGQIFT
  1141  IRRCPSTDPE EAIEDVEGPS ETAADPEELA KDQEGGASSS QAEKELTDSP ATSKRISFPG
  1201  SSESPLSSKR PKTAEEIKPE QMYQCPYCKY SNADVNRLRV HAMTQHSVQP MLRCPLCQDM
  1261  LNNKIHLQLH LTHLHSVAPD CVEKLIMTVT TPEMVMPSSM FLPAAVPDRD GNSNLEEAGK
  1321  QPETSEDLGK NILPSASTEQ SGDLKPSPAD PGSVREDSGF ICWKKGCNQV FKTSAALQTH
  1381  FNEVHAKRPQ LPVSDRHVYK YRCNQCSLAF KTIEKLQLHS QYHVIRAATM CCLCQRSFRT
  1441  FQALKKHLET SHLELSEADI QQLYGGLLAN GDLLAMGDPT LAEDHTIIVE EDKEEESDLE
  1501  DKQSPTGSDS GSVQEDSGSE PKRALPFRKG PNFTMEKFLD PSRPYKCTVC KESFTQKNIL
  1561  LVHYNSVSHL HKLKRALQES ATGQPEPTSS PDNKPFKCNT CNVAYSQSST LEIHMRSVLH
  1621  QTKARAAKLE AASGSSNGTG NSSSISLSSS TPSPVSTSGS NTFTTSNPSS AGIAPSSNLL
  1681  SQVPTESVGM PPLGNPIGAN IASPSEPKEA NRKKLADMIA SRQQQQQQQQ QQQQQQQQQQ
  1741  QAQTLAQAQA QVQAHLQQEL QQQAALIQSQ LFNPTLLPHF PMTTETLLQL QQQQHLLFPF
  1801  YIPSAEFQLN PEVSLPVTSG ALTLTGTGPG LLEDLKAQVQ VPQQSHQQIL PQQQQNQLSI
  1861  AQSHSALLQP SQHPEKKNKL VIKEKEKESQ RERDSAEGGE GNTGPKETLP DALKAKEKKE
  1921  LAPGGGSEPS MLPPRIASDA RGNATKALLE NFGFELVIQY NENKQKVQKK NGKTDQGENL
  1981  EKLECDSCGK LFSNILILKS HQEHVHQNYF PFKQLERFAK QYRDHYDKLY PLRPQTPEPP
  2041  PPPPPPPPPP LPAAPPQPAS TPAIPASAPP ITSPTIAPAQ PSVPLTQLSM PMELPIFSPL
  2101  MMQTMPLQTL PAQLPPQLGP VEPLPADLAQ LYQHQLNPTL LQQQNKRPRT RITDDQLRVL
  2161  RQYFDINNSP SEEQIKEMAD KSGLPQKVIK HWFRNTLFKE RQRNKDSPYN FSNPPITSLE
  2221  ELKIDSRPPS PEPPKQEYWG SKRSSRTRFT DYQLRVLQDF FDANAYPKDD EFEQLSNLLN
  2281  LPTRVIVVWF QNARQKARKN YENQGEGKDG ERRELTNDRY IRTSNLNYQC KKCSLVFQRI
  2341  FDLIKHQKKL CYKDEDEEGQ DDSQNEDSMD AMEILTPTSS SCSTPMPSQA YSAPAPSANN
  2401  TASSAFLQLT AEAEELATFN SKTEAGDEKP KLAEAPSAQP NQTQEKQGQP KPELQQQEQP
  2461  EQKTNTPQQK LPQLVSLPSL PQPPPQAPPP QCPLPQSSPS PSQLSHLPLK PLHTSTPQQL
  2521  ANLPPQLIPY QCDQCKLAFP SFEHWQEHQQ LHFLSAQNQF IHPQFLDRSL DMPFMLFDPS
  2581  NPLLASQLLS GAIPQIPASS ATSPSTPTST MNTLKRKLEE KASASPGEND SGTGGEEPQR
  2641  DKRLRTTITP EQLEILYQKY LLDSNPTRKM LDHIAHEVGL KKRVVQVWFQ NTRARERKGQ
  2701  FRAVGPAQAH RRCPFCRALF KAKTALEAHI RSRHWHEAKR AGYNLTLSAM LLDCDGGLQM
  2761  KGDIFDGTSF SHLPPSSSDG QGVPLSPVSK TMELSPRTLL SPSSIKVEGI EDFESPSMSS
  2821  VNLNFDQTKL DNDDCSSVNT AITDTTTGDE GNADNDSATG IATETKSSSA PNEGLTKAAM
  2881  MAMSEYEDRL SSGLVSPAPS FYSKEYDNEG TVDYSETSSL ADPCSPSPGA SGSAGKSGDS
  2941  GDRPGQKRFR TQMTNLQLKV LKSCFNDYRT PTMLECEVLG NDIGLPKRVV QVWFQNARAK
  3001  EKKSKLSMAK HFGINQTSYE GPKTECTLCG IKYSARLSVR DHIFSQQHIS KVKDTIGSQL
  3061  DKEKEYFDPA TVRQLMAQQE LDRIKKANEV LGLAAQQQGM FDNTPLQALN LPTAYPALQG
  3121  IPPVLLPGLN SPSLPGFTPS NTALTSPKPN LMGLPSTTVP SPGLPTSGLP NKPSSASLSS
  3181  PTPAQATMAM GPQQPPQQQQ QQQQPQVQQP PPPPAAQPPP TPQLPLQQQQ QRKDKDSEKV
  3241  KEKEKAHKGK GEPLPVPKKE KGEAPTATAA TISAPLPTME YAVDPAQLQA LQAALTSDPT
  3301  ALLTSQFLPY FVPGFSPYYA PQIPGALQSG YLQPMYGMEG LFPYSPALSQ ALMGLSPGSL
  3361  LQQYQQYQQS LQEAIQQQQQ RQLQQQQQQK VQQQQPKASQ TPVPPGAPSP DKDPAKESPK
  3421  PEEQKNTPRE VSPLLPKLPE EPEAESKSAD SLYDPFIVPK VQYKLVCRKC QAGFSDEEAA
  3481  RSHLKSLCFF GQSVVNLQEM VLHVPTGGGG GGSGGGGGGG GGGGGGGSYH CLACESALCG
  3541  EEALSQHLES ALHKHRTITR AARNAKEHPS LLPHSACFPD PSTASTSQSA AHSNDSPPPP
  3601  SAAAPSSASP HASRKSWPQV VSRASAAKPP SFPPLSSSST VTSSSCSTSG VQPSMPTDDY
  3661  SEESDTDLSQ KSDGPASPVE GPKDPSCPKD SGLTSVGTDT FRL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ZFHX3 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: 18 nTPM

Expression across tissuesHPA

Tissue

blood vessel: 18 nTPM
tongue: 10 nTPM
skeletal muscle: 9.2 nTPM
parathyroid gland: 9.1 nTPM
thyroid gland: 6.9 nTPM
prostate: 6.4 nTPM

Single-cell type

vascular smooth muscle cells: 1,813 nCPM
retinal ganglion cells: 1,734 nCPM
microglia: 1,035 nCPM
prostatic glandular cells: 821 nCPM
tuft cells: 795 nCPM
retinal amacrine cells: 753 nCPM

Immune cell

NK-cell: 0.4 nTPM
classical monocyte: 0.3 nTPM
intermediate monocyte: 0.2 nTPM
non-classical monocyte: 0.2 nTPM
plasmacytoid DC: 0.2 nTPM
myeloid DC: 0.1 nTPM

Brain region

cerebral cortex: 667 nTPM
medulla oblongata: 155 nTPM
hippocampal formation: 150 nTPM
white matter: 122 nTPM
pons: 112 nTPM
midbrain: 43 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ZFHX3.

Disease | AllUniProt

Conditions ZFHX3 is implicated in, by any mechanism.

Atrial fibrillation, familial, 8 (ATFB8) MIM:613055
Spinocerebellar ataxia 4 (SCA4) MIM:600223

Disease | GeneticClinVar

44 pathogenic / likely-pathogenic of 964 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

ZFHX3-related disorder
Neurodevelopmental disorder
Epilepsy, idiopathic generalized 20
Moyamoya angiopathy
ZFHX3-associated 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): 0.14
gnomAD pLI: 1
gnomAD missense Z: -1.23
DepMap mean gene effect: 0.01
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

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of ZFHX3 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 ZFHX3 as an antibody target. Whether an autoantibody or antibody against ZFHX3 could matter depends on whether native ZFHX3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ZFHX3 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 ZFHX3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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