This gene encodes a multi-domain protein involved in signaling and organization of cell junctions during embryogenesis. It has also been identified as the fusion partner of acute lymphoblastic leukemia (ALL-1) gene, involved in acute myeloid leukemias with t(6;11)(q27;q23) translocation. Alternatively spliced transcript variants encoding different isoforms have been described f... See more...

Aliases for AFDN Gene

Aliases for AFDN Gene

  • Afadin, Adherens Junction Formation Factor 2 3 5
  • AF6 2 3 4
  • Myeloid/Lymphoid Or Mixed-Lineage Leukemia; Translocated To, 4 2 3
  • ALL1-Fused Gene From Chromosome 6 Protein 3 4
  • Protein AF-6 3 4
  • Afadin 3 4
  • MLLT4 3 4
  • Myeloid/Lymphoid Or Mixed-Lineage Leukemia (Trithorax Homolog, Drosophila); Translocated To, 4 3
  • Afadin Adherens Junction Formation Factor 4
  • L-Afadin 3
  • MLL-AF6 3
  • AFDN 5
  • AF-6 2

External Ids for AFDN Gene

Previous HGNC Symbols for AFDN Gene

  • MLLT4

Summaries for AFDN Gene

Entrez Gene Summary for AFDN Gene

  • This gene encodes a multi-domain protein involved in signaling and organization of cell junctions during embryogenesis. It has also been identified as the fusion partner of acute lymphoblastic leukemia (ALL-1) gene, involved in acute myeloid leukemias with t(6;11)(q27;q23) translocation. Alternatively spliced transcript variants encoding different isoforms have been described for this gene, however, not all have been fully characterized.[provided by RefSeq, May 2011]

GeneCards Summary for AFDN Gene

AFDN (Afadin, Adherens Junction Formation Factor) is a Protein Coding gene. Diseases associated with AFDN include Cleft Lip/Palate-Ectodermal Dysplasia Syndrome and Leukemia. Among its related pathways are Blood-Brain Barrier and Immune Cell Transmigration: VCAM-1/CD106 Signaling and Ras signaling pathway.

UniProtKB/Swiss-Prot Summary for AFDN Gene

  • Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs) (By similarity). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton (PubMed:11024295). May play a key role in the organization of epithelial structures of the embryonic ectoderm (By similarity). Essential for the organization of adherens junctions (PubMed:30463011).

Gene Wiki entry for AFDN Gene

Additional gene information for AFDN Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for AFDN Gene

Genomics for AFDN Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for AFDN Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH06J167826 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 619.9 +2.6 2611 9.2 HNRNPL GATAD2A PRDM10 REST ZNF629 TFE3 ZNF512 LEF1 IKZF1 ZNF692 AFDN AFDN-DT LINC01558 LOC441179 ENSG00000285212 piR-46757 HGC6.3
GH06J167795 Promoter/Enhancer 1.3 EPDnew Ensembl ENCODE 600.3 -29.9 -29916 3 HNRNPL REST SP1 NRF1 ZBTB2 YY1 JUND PCBP1 NR2F2 CEBPG LOC441179 LINC01558 ENSG00000285212 AFDN LOC105378132
GH06J167733 Enhancer 1.1 Ensembl ENCODE 20.3 -92.1 -92063 2.6 HNRNPL GATAD2A TFE3 SOX13 NFKBIZ RCOR2 RXRB IRF2 SP1 GABPA AFDN HSALNG0055195 lnc-FRMD1-9 LOC105378132
GH06J166997 Promoter/Enhancer 2.2 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 10.1 -826.9 -826878 5 SP1 HNRNPL TEAD4 REST RFX1 SOX13 KDM1A CTCF ZNF692 POLR2A RNASET2 ENSG00000227598 CEP43 ENSG00000272980 ENSG00000285730 MIR3939 HNRNPA1P49 AFDN GPR31 CCR6
GH06J167706 Enhancer 0.7 Ensembl 25.9 -120.4 -120363 1.6 HDAC1 SOX6 NRF1 SOX13 ARID3A DPF2 RUNX3 HES1 RUNX1 NR2F1 AFDN LINC01558 HSALNG0055193 lnc-AFDN-8 LOC105378132
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around AFDN on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for AFDN

Genomic Locations for AFDN Gene

Genomic Locations for AFDN Gene
chr6:167,826,564-167,972,023
(GRCh38/hg38)
Size:
145,460 bases
Orientation:
Plus strand
chr6:168,227,602-168,372,703
(GRCh37/hg19)
Size:
145,102 bases
Orientation:
Plus strand

Genomic View for AFDN Gene

Genes around AFDN on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
AFDN Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for AFDN Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for AFDN Gene

Proteins for AFDN Gene

  • Protein details for AFDN Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P55196-AFAD_HUMAN
    Recommended name:
    Afadin
    Protein Accession:
    P55196
    Secondary Accessions:
    • O75087
    • O75088
    • O75089
    • Q59FP0
    • Q5TIG6
    • Q5TIG7
    • Q9NSN7
    • Q9NU92

    Protein attributes for AFDN Gene

    Size:
    1824 amino acids
    Molecular mass:
    206804 Da
    Quaternary structure:
    • Homodimer. Interacts with F-actin, nectin and NECTIN3. Essential for the association of nectin and E-cadherin. Isoform 1/s-afadin does not interact with F-actin. Interacts with ZO-1 and occludin, but probably in an indirect manner. Interacts with RIT1 and RIT2 (By similarity). Interacts with NRXN1 and BCR. Interacts with ADAM10; the interaction locks ADAM10 at adherens junctions following ADAM10 recruitment to adherens junctions by TSPAN33 (PubMed:30463011).
    SequenceCaution:
    • Sequence=CAB82312.1; Type=Frameshift; Evidence={ECO:0000305};
    Miscellaneous:
    • [Isoform 1]: May be due to intron retention.
    • [Isoform 2]: May be due to intron retention.

    Three dimensional structures from OCA and Proteopedia for AFDN Gene

    Alternative splice isoforms for AFDN Gene

neXtProt entry for AFDN Gene

Post-translational modifications for AFDN Gene

  • Glycosylation at Asn1263
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for AFDN Gene

Domains & Families for AFDN Gene

Gene Families for AFDN Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for AFDN Gene

InterPro:
Blocks:
  • Forkhead-associated (FHA)
  • PDZ/DHR/GLGF domain
  • RA domain
  • Dilute (DIL) domain
ProtoNet:

Suggested Antigen Peptide Sequences for AFDN Gene

GenScript: Design optimal peptide antigens:
  • ALL1-fused gene from chromosome 6 protein (AFAD_HUMAN)
  • Myeloid/lymphoid or mixed-lineage leukemia (Trithorax homolog, Drosophila) (Q5JPV5_HUMAN)
  • Myeloid/lymphoid or mixed-lineage leukemia (Trithorax homolog, Drosophila) (Q5TIH0_HUMAN)
  • Myeloid/lymphoid or mixed-lineage leukemia (Trithorax homolog, Drosophila) (Q5TIH1_HUMAN)
  • Myeloid/lymphoid or mixed-lineage leukemia (Trithorax homolog, Drosophila) (Q96C95_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P55196

UniProtKB/Swiss-Prot:

AFAD_HUMAN :
  • The PDZ/DHR domain interacts with the C-terminus of nectin and the Pro-rich C-terminal domain interacts with F-actin.
Domain:
  • The PDZ/DHR domain interacts with the C-terminus of nectin and the Pro-rich C-terminal domain interacts with F-actin.
genes like me logo Genes that share domains with AFDN: view

Function for AFDN Gene

Molecular function for AFDN Gene

UniProtKB/Swiss-Prot Function:
Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs) (By similarity). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton (PubMed:11024295). May play a key role in the organization of epithelial structures of the embryonic ectoderm (By similarity). Essential for the organization of adherens junctions (PubMed:30463011).

Phenotypes From GWAS Catalog for AFDN Gene

Gene Ontology (GO) - Molecular Function for AFDN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IEA,IPI 17491594
GO:0008022 protein C-terminus binding TAS 10856295
GO:0017016 Ras GTPase binding IPI 23885123
GO:0045296 cadherin binding HDA 25468996
GO:0050839 cell adhesion molecule binding IEA,IBA 21873635
genes like me logo Genes that share ontologies with AFDN: view
genes like me logo Genes that share phenotypes with AFDN: view

Animal Models for AFDN Gene

MGI Knock Outs for AFDN:
  • Afdn Afdn<tm1Mrcr>
  • Afdn Afdn<tm1Ytk>
  • Afdn Afdn<tm1a(EUCOMM)Hmgu>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for AFDN

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for AFDN Gene

Localization for AFDN Gene

Subcellular locations from UniProtKB/Swiss-Prot for AFDN Gene

Cell junction, adherens junction. Note=Not found at cell-matrix AJs. {ECO:0000250 UniProtKB:O35889}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for AFDN gene
Compartment Confidence
plasma membrane 5
nucleus 5
cytosol 5
cytoskeleton 3
extracellular 2
endoplasmic reticulum 2
endosome 2
mitochondrion 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cell Junctions (4)
  • Plasma membrane (4)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for AFDN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol IDA,TAS --
GO:0005886 plasma membrane IDA --
GO:0005911 cell-cell junction IEA,IDA 19461049
genes like me logo Genes that share ontologies with AFDN: view

Pathways & Interactions for AFDN Gene

genes like me logo Genes that share pathways with AFDN: view

Pathways by source for AFDN Gene

3 GeneGo (Thomson Reuters) pathways for AFDN Gene
  • Cell adhesion Tight junctions
  • Cell adhesion_Cadherin-mediated cell adhesion
  • Cell adhesion_Endothelial cell contacts by junctional mechanisms
5 Qiagen pathways for AFDN Gene
  • Ephrin-Eph Signaling
  • Epithelial Adherens Junctions
  • Epithelial Tight Junctions
  • Germ Cell-Sertoli Cell Junction Dynamics
  • Sertoli-Sertoli Cell Junction Dynamics
2 Cell Signaling Technology pathways for AFDN Gene

SIGNOR curated interactions for AFDN Gene

Activates:

Gene Ontology (GO) - Biological Process for AFDN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007155 cell adhesion TAS 10856295
GO:0007165 signal transduction IEA --
GO:0007267 cell-cell signaling TAS 8242616
GO:0010628 positive regulation of gene expression IMP 25893857
GO:0021537 telencephalon development IEA --
genes like me logo Genes that share ontologies with AFDN: view

Drugs & Compounds for AFDN Gene

(3) Drugs for AFDN Gene - From: DrugBank and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
(5R)-2-sulfanyl-5-[4-(trifluoromethyl)benzyl]-1,3-thiazol-4(5H)-one Experimental Pharma Target 0
genes like me logo Genes that share compounds with AFDN: view

Transcripts for AFDN Gene

mRNA/cDNA for AFDN Gene

8 REFSEQ mRNAs :
21 NCBI additional mRNA sequence :
22 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for AFDN

Alternative Splicing Database (ASD) splice patterns (SP) for AFDN Gene

No ASD Table

Relevant External Links for AFDN Gene

GeneLoc Exon Structure for
AFDN

Expression for AFDN Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for AFDN

Evidence on tissue expression from TISSUES for AFDN Gene

  • Nervous system(4.9)
  • Liver(4.6)
  • Lung(3.6)
  • Spleen(3.2)
  • Kidney(3)
  • Skin(2.9)
  • Blood(2.9)
  • Intestine(2.9)
  • Heart(2.8)
  • Lymph node(2.8)
  • Bone marrow(2.5)
  • Muscle(2.5)
  • Stomach(2.3)
  • Pancreas(2.3)
  • Thyroid gland(2.3)
  • Eye(2.3)
genes like me logo Genes that share expression patterns with AFDN: view

No data available for mRNA expression in normal human tissues , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for AFDN Gene

Orthologs for AFDN Gene

This gene was present in the common ancestor of animals.

Orthologs for AFDN Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia MLLT4 30 31
  • 98.23 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia MLLT4 30 31
  • 88.07 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Mllt4 30
  • 87.93 (n)
Mouse
(Mus musculus)
Mammalia Mllt4 30 31
  • 87 (n)
OneToOne
Afdn 17
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 86 (a)
OneToMany
-- 31
  • 84 (a)
OneToMany
-- 31
  • 78 (a)
OneToMany
-- 31
  • 77 (a)
OneToMany
Cow
(Bos Taurus)
Mammalia MLLT4 30 31
  • 81.45 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia MLLT4 31
  • 62 (a)
OneToOne
Chicken
(Gallus gallus)
Aves MLLT4 30 31
  • 80.9 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia MLLT4 31
  • 80 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia mllt4 30
  • 73.37 (n)
Str.20348 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.22528 30
Zebrafish
(Danio rerio)
Actinopterygii mllt4 30 31
  • 71.06 (n)
OneToMany
MLLT4 (3 of 3) 31
  • 58 (a)
OneToMany
MLLT4 (2 of 3) 31
  • 44 (a)
OneToMany
Fruit Fly
(Drosophila melanogaster)
Insecta cno 31
  • 31 (a)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea afd-1 30 31
  • 47.68 (n)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 44 (a)
OneToOne
Species where no ortholog for AFDN was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for AFDN Gene

ENSEMBL:
Gene Tree for AFDN (if available)
TreeFam:
Gene Tree for AFDN (if available)
Aminode:
Evolutionary constrained regions (ECRs) for AFDN: view image

Paralogs for AFDN Gene

No data available for Paralogs for AFDN Gene

Variants for AFDN Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for AFDN Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
771409 Benign: not provided 167,948,301(+) G/A SYNONYMOUS_VARIANT
rs1057519562 Uncertain Significance: not specified 167,915,425(+) ATC/TGA NONSENSE
rs35140809 Uncertain Significance: not specified 167,896,967(+) A/G MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for AFDN Gene

Structural Variations from Database of Genomic Variants (DGV) for AFDN Gene

Variant ID Type Subtype PubMed ID
dgv11062n54 CNV gain 21841781
dgv11063n54 CNV gain 21841781
dgv1853e212 CNV gain 25503493
dgv217e55 CNV gain 17911159
dgv218e55 CNV gain 17911159
dgv27e196 CNV duplication 17116639
dgv6199n100 CNV gain 25217958
dgv61n64 CNV gain 17921354
dgv791n27 CNV gain 19166990
esv1558245 CNV deletion 17803354
esv23528 CNV gain+loss 19812545
esv2422263 CNV duplication 17116639
esv2422479 CNV duplication 17116639
esv2572068 CNV deletion 19546169
esv2678919 CNV deletion 23128226
esv2759493 CNV gain 17122850
esv2761051 CNV gain 21179565
esv2763949 CNV gain 21179565
esv32818 CNV gain 17666407
esv3350230 CNV insertion 20981092
esv3611675 CNV loss 21293372
esv3611678 CNV gain 21293372
esv3611679 CNV gain 21293372
esv3611680 CNV gain 21293372
esv991018 CNV deletion 20482838
nsv1027114 CNV gain 25217958
nsv1030168 CNV gain 25217958
nsv1074037 CNV deletion 25765185
nsv1145112 CNV deletion 24896259
nsv442020 CNV gain 18776908
nsv509173 CNV insertion 20534489
nsv511926 CNV loss 21212237
nsv515568 CNV gain+loss 19592680
nsv5593 CNV insertion 18451855
nsv8004 CNV gain 18304495
nsv820650 CNV deletion 20802225
nsv830864 CNV gain 17160897
nsv830865 CNV gain 17160897
nsv949897 CNV deletion 24416366

Variation tolerance for AFDN Gene

Residual Variation Intolerance Score: 2.63% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.78; 58.16% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for AFDN Gene

Human Gene Mutation Database (HGMD)
AFDN
SNPedia medical, phenotypic, and genealogical associations of SNPs for
AFDN

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for AFDN Gene

Disorders for AFDN Gene

MalaCards: The human disease database

(3) MalaCards diseases for AFDN Gene - From: DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search AFDN in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

AFAD_HUMAN
  • Note=A chromosomal aberration involving AFDN is associated with acute leukemias. Translocation t(6;11)(q27;q23) with KMT2A/MLL1. The result is a rogue activator protein.
genes like me logo Genes that share disorders with AFDN: view

No data available for Genatlas for AFDN Gene

Publications for AFDN Gene

  1. Cloning of the ALL-1 fusion partner, the AF-6 gene, involved in acute myeloid leukemias with the t(6;11) chromosome translocation. (PMID: 8242616) Prasad R … Kuriyama K (Cancer research 1993) 2 3 4 23
  2. Nectin and afadin: novel organizers of intercellular junctions. (PMID: 12456712) Takai Y … Nakanishi H (Journal of cell science 2003) 3 4 23
  3. Human nectin3/PRR3: a novel member of the PVR/PRR/nectin family that interacts with afadin. (PMID: 11024295) Reymond N … Lopez M (Gene 2000) 3 4 23
  4. Complete genomic structure DNA polymorphisms, and alternative splicing of the human AF-6 gene. (PMID: 9679199) Saito S … Nakamura Y (DNA research : an international journal for rapid publication of reports on genes and genomes 1998) 3 4 23
  5. A Dock-and-Lock Mechanism Clusters ADAM10 at Cell-Cell Junctions to Promote α-Toxin Cytotoxicity. (PMID: 30463011) Shah J … Citi S (Cell reports 2018) 3 4

Products for AFDN Gene

Sources for AFDN Gene