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    EYA4 EYA transcriptional coactivator and phosphatase 4 [ Homo sapiens (human) ]

    Gene ID: 2070, updated on 27-Nov-2024

    Summary

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    Official Symbol
    EYA4provided by HGNC
    Official Full Name
    EYA transcriptional coactivator and phosphatase 4provided by HGNC
    Primary source
    HGNC:HGNC:3522
    See related
    Ensembl:ENSG00000112319 MIM:603550; AllianceGenome:HGNC:3522
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CMD1J; DFNA10
    Summary
    This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may act as a transcriptional activator through its protein phosphatase activity, and it may be important for eye development, and for continued function of the mature organ of Corti. Mutations in this gene are associated with postlingual, progressive, autosomal dominant hearing loss at the deafness, autosomal dominant non-syndromic sensorineural 10 locus. The encoded protein is also a putative oncogene that mediates DNA repair, apoptosis, and innate immunity following DNA damage, cellular damage, and viral attack. Defects in this gene are also associated with dilated cardiomyopathy 1J. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]
    Expression
    Broad expression in prostate (RPKM 1.8), kidney (RPKM 1.5) and 15 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See EYA4 in Genome Data Viewer
    Location:
    6q23.2
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (133240593..133532128)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (134429416..134720956)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (133562495..133853266)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 326 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_89898 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_89904 Neighboring gene MT-CYB pseudogene 4 Neighboring gene serine/arginine repetitive matrix protein 1-like Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:133562838-133563732 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:133563733-133564625 Neighboring gene uncharacterized LOC124901403 Neighboring gene NANOG hESC enhancer GRCh37_chr6:133731684-133732216 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:133802579-133802752 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr6:133826289-133827488 Neighboring gene heat shock protein family E (Hsp10) member 1 pseudogene 21 Neighboring gene TCF21 antisense RNA inducing promoter demethylation Neighboring gene GATA motif-containing MPRA enhancer 179 Neighboring gene MPRA-validated peak6128 silencer Neighboring gene ferritin heavy chain 1 pseudogene 26 Neighboring gene uncharacterized LOC124901402

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. A novel splice site mutation in EYA4 causes DFNA10 hearing loss. Hildebrand MS, et al. Am J Med Genet A, 2007 Jul 15. PMID 17568404
    2. EYA4 serves as a prognostic biomarker in hepatocellular carcinoma and suppresses tumour angiogenesis and metastasis. Gu F, et al. J Cell Mol Med, 2019 Jun. PMID 30957411, Free PMC Article
    3. Identification of a novel missense eya4 mutation causing autosomal dominant non‑syndromic hearing loss in a chinese family. Xiao SY, et al. Cell Mol Biol (Noisy-le-grand), 2019 Mar 31. PMID 30942159
    4. Methylated eyes absent 4 (EYA4) gene promotor in non-neoplastic mucosa of ulcerative colitis patients with colorectal cancer: evidence for a field effect. Kisiel JB, et al. Inflamm Bowel Dis, 2013 Sep. PMID 23867875, Free PMC Article
    5. EYA4 Promotes Cell Proliferation Through Downregulation of p27Kip1 in Glioma. Li Z, et al. Cell Physiol Biochem, 2018. PMID 30231237

    See all (94) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. EYA4 promotes breast cancer progression and metastasis through its role in replication stress avoidance.
      Title: EYA4 promotes breast cancer progression and metastasis through its role in replication stress avoidance.
    2. Aberrant DNA methylation and expression of EYA4 in gastric cardia intestinal metaplasia.
      Title: Aberrant DNA methylation and expression of EYA4 in gastric cardia intestinal metaplasia.
    3. Identification of a novel CNV at the EYA4 gene in a Chinese family with autosomal dominant nonsyndromic hearing loss.
      Title: Identification of a novel CNV at the EYA4 gene in a Chinese family with autosomal dominant nonsyndromic hearing loss.
    4. Identification of a Novel Copy Number Variation of EYA4 Causing Autosomal Dominant Non-syndromic Hearing Loss.
      Title: Identification of a Novel Copy Number Variation of EYA4 Causing Autosomal Dominant Non-syndromic Hearing Loss.
    5. Prognostic Role of EYA4 in Lower Grade Glioma with IDH1 Mutation and 1p19q Co-Deletion.
      Title: Prognostic Role of EYA4 in Lower Grade Glioma with IDH1 Mutation and 1p19q Co-Deletion.
    6. Early truncation of the N-terminal variable region of EYA4 gene causes dominant hearing loss without cardiac phenotype.
      Title: Early truncation of the N-terminal variable region of EYA4 gene causes dominant hearing loss without cardiac phenotype.
    7. Genome-first approach to rare EYA4 variants and cardio-auditory phenotypes in adults.
      Title: Genome-first approach to rare EYA4 variants and cardio-auditory phenotypes in adults.
    8. Insights into the pathophysiology of DFNA10 hearing loss associated with novel EYA4 variants.
      Title: Insights into the pathophysiology of DFNA10 hearing loss associated with novel EYA4 variants.
    9. Prevalence and clinical features of hearing loss caused by EYA4 variants.
      Title: Prevalence and clinical features of hearing loss caused by EYA4 variants.
    10. EYA4 is a novel tumour suppressor in HCC and a new prognostic biomarker and therapeutic target in HCC.
      Title: EYA4 serves as a prognostic biomarker in hepatocellular carcinoma and suppresses tumour angiogenesis and metastasis.
    Submit: New GeneRIF Correction See all GeneRIFs (50)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2020-01-22)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2020-01-22)

    ClinGen Genome Curation PagePubMed

    EBI GWAS Catalog

    Description
    A genome-wide association study identifies protein quantitative trait loci (pQTLs).
    EBI GWAS Catalog
    Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
    EBI GWAS Catalog
    Genomic association analysis identifies multiple loci influencing antihypertensive response to an angiotensin II receptor blocker.
    EBI GWAS Catalog
    Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables histone H2AXY142 phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables non-membrane spanning protein tyrosine phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein tyrosine phosphatase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein tyrosine phosphatase activity, metal-dependent IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in DNA repair IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in anatomical structure morphogenesis TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in cell differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in inner ear development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of extrinsic apoptotic signaling pathway in absence of ligand IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of DNA repair IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in visual perception TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    eyes absent homolog 4
    Names
    dJ78N10.1 (eyes absent)
    eyes absent-like protein 4
    NP_001287941.1
    NP_001287942.1
    NP_001357387.1
    NP_001357388.1
    NP_004091.3
    NP_742101.2
    NP_742103.1
    XP_005266908.1
    XP_016865857.1
    XP_016865858.1
    XP_016865860.1
    XP_016865862.1
    XP_016865863.1
    XP_047274231.1
    XP_047274232.1
    XP_047274233.1
    XP_047274234.1
    XP_047274235.1
    XP_047274236.1
    XP_047274237.1
    XP_047274238.1
    XP_047274239.1
    XP_047274240.1
    XP_047274241.1
    XP_047274242.1
    XP_047274243.1
    XP_047274244.1
    XP_054210426.1
    XP_054210427.1
    XP_054210428.1
    XP_054210429.1
    XP_054210430.1
    XP_054210431.1
    XP_054210432.1
    XP_054210433.1
    XP_054210434.1
    XP_054210435.1
    XP_054210436.1
    XP_054210437.1
    XP_054210438.1
    XP_054210439.1
    XP_054210440.1
    XP_054210441.1
    XP_054210442.1
    XP_054210443.1
    XP_054210444.1
    XP_054210445.1
    XP_054210446.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011596.2 RefSeqGene

      Range
      5001..295772
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_418

    mRNA and Protein(s)

    1. NM_001301012.2 → NP_001287941.1  eyes absent homolog 4 isoform e

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) has multiple differences in its coding region, compared to variant 1. The resulting isoform (e) is shorter than isoform a.
      Source sequence(s)
      AK295798, AK301950, AL121959, AL450270, AW613879
      Consensus CDS
      CCDS75523.1
      UniProtKB/TrEMBL
      A0A0S2Z3Q2, E7ESD5
      Related
      ENSP00000516341.1, ENST00000706301.1
      Conserved Domains (2) summary
      TIGR01658
      Location:314 → 585
      EYA-cons_domain; eyes absent protein conserved domain
      pfam12533
      Location:153 → 232
      Neuro_bHLH; Neuronal helix-loop-helix transcription factor

    2. NM_001301013.2 → NP_001287942.1  eyes absent homolog 4 isoform f

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) contains an alternate in-frame segment of the 5' coding region, compared to variant 1. The resulting isoform (f) is longer than isoform a.
      Source sequence(s)
      AK299378, AK301950, AL121959, AL450270, AW613879, Y17114
      Consensus CDS
      CCDS75521.1
      UniProtKB/TrEMBL
      B4DRQ6, F2Z2Y1
      Related
      ENSP00000432770.1, ENST00000531901.5
      Conserved Domains (3) summary
      TIGR01658
      Location:374 → 645
      EYA-cons_domain; eyes absent protein conserved domain
      pfam00702
      Location:376 → 621
      Hydrolase; haloacid dehalogenase-like hydrolase
      pfam12533
      Location:207 → 286
      Neuro_bHLH; Neuronal helix-loop-helix transcription factor

    3. NM_001370458.1 → NP_001357387.1  eyes absent homolog 4 isoform g

      Status: REVIEWED

      Source sequence(s)
      AL024497, AL121959, AL450270
      Consensus CDS
      CCDS94004.1
      UniProtKB/TrEMBL
      B4DRQ6, E9PLN6
      Related
      ENSP00000433219.1, ENST00000525849.7
      Conserved Domains (1) summary
      cd02601
      Location:345 → 616
      HAD_Eya; protein tyrosine phosphatase domain of the nuclear transcription factor of Eyes absent (Eya) and related phosphatase domains

    4. NM_001370459.1 → NP_001357388.1  eyes absent homolog 4 isoform h

      Status: REVIEWED

      Source sequence(s)
      AL024497, AL121959, AL450270
      Consensus CDS
      CCDS94005.1
      UniProtKB/TrEMBL
      A0A8C8KDW0, E7ESD5
      Related
      ENSP00000347294.4, ENST00000355167.8
      Conserved Domains (1) summary
      cd02601
      Location:320 → 591
      HAD_Eya; protein tyrosine phosphatase domain of the nuclear transcription factor of Eyes absent (Eya) and related phosphatase domains

    5. NM_004100.5 → NP_004091.3  eyes absent homolog 4 isoform a

      See identical proteins and their annotated locations for NP_004091.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes isoform a, which is more abundant in adult brain.
      Source sequence(s)
      AL450270, AW613879, BC014193, BX490250, DA760903, Y17114
      Consensus CDS
      CCDS5165.1
      UniProtKB/Swiss-Prot
      B7Z7F7, O95464, O95677, O95679, Q8IW39, Q9NTR7
      UniProtKB/TrEMBL
      B4DRQ6
      Related
      ENSP00000347434.7, ENST00000355286.12
      Conserved Domains (3) summary
      TIGR01658
      Location:368 → 639
      EYA-cons_domain; eyes absent protein conserved domain
      pfam00702
      Location:370 → 615
      Hydrolase; haloacid dehalogenase-like hydrolase
      pfam12533
      Location:207 → 286
      Neuro_bHLH; Neuronal helix-loop-helix transcription factor

    6. NM_172103.4 → NP_742101.2  eyes absent homolog 4 isoform b

      See identical proteins and their annotated locations for NP_742101.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame segment of the 5' coding region, compared to variant 1. The resulting isoform (b) is shorter than isoform a.
      Source sequence(s)
      AL450270, AW613879, BC014193, BC041063, BX490250, Y17114
      Consensus CDS
      CCDS43506.1
      UniProtKB/TrEMBL
      A0A0S2Z3V9, B4DRQ6
      Related
      ENSP00000404558.3, ENST00000431403.3
      Conserved Domains (2) summary
      cd02601
      Location:345 → 616
      HAD_Eya; protein tyrosine phosphatase domain of the nuclear transcription factor of Eyes absent (Eya) and related phosphatase domains
      cl25764
      Location:109 → 260
      PAT1; Topoisomerase II-associated protein PAT1

    7. NM_172105.4 → NP_742103.1  eyes absent homolog 4 isoform d

      See identical proteins and their annotated locations for NP_742103.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) contains an alternate in-frame exon in the 3' coding region, compared to variant 1. The resulting isoform (d) is the same size but has a region of difference in the C-terminal, compared to isoform a.
      Source sequence(s)
      AJ007994, AL450270, AW613879, BC014193, BX490250, DA760903, Y17114
      UniProtKB/TrEMBL
      B4DRQ6
      Conserved Domains (2) summary
      TIGR01658
      Location:368 → 639
      EYA-cons_domain; eyes absent protein conserved domain
      pfam12533
      Location:207 → 286
      Neuro_bHLH; Neuronal helix-loop-helix transcription factor

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      133240593..133532128
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017010368.3 → XP_016865857.1  eyes absent homolog 4 isoform X1

      UniProtKB/TrEMBL
      B4DRQ6

    2. XM_047418278.1 → XP_047274234.1  eyes absent homolog 4 isoform X8

    3. XM_047418275.1 → XP_047274231.1  eyes absent homolog 4 isoform X4

    4. XM_047418279.1 → XP_047274235.1  eyes absent homolog 4 isoform X9

    5. XM_047418282.1 → XP_047274238.1  eyes absent homolog 4 isoform X12

      UniProtKB/TrEMBL
      E9PLN6

    6. XM_047418276.1 → XP_047274232.1  eyes absent homolog 4 isoform X6

    7. XM_047418285.1 → XP_047274241.1  eyes absent homolog 4 isoform X15

    8. XM_047418286.1 → XP_047274242.1  eyes absent homolog 4 isoform X18

      UniProtKB/TrEMBL
      A0A8C8KDW0

    9. XM_047418288.1 → XP_047274244.1  eyes absent homolog 4 isoform X20

      UniProtKB/TrEMBL
      A0A0S2Z3Q2
      Related
      ENSP00000395916.2, ENST00000452339.6

    10. XM_017010373.3 → XP_016865862.1  eyes absent homolog 4 isoform X16

      UniProtKB/TrEMBL
      E7ESD5

    11. XM_047418277.1 → XP_047274233.1  eyes absent homolog 4 isoform X7

    12. XM_005266851.6 → XP_005266908.1  eyes absent homolog 4 isoform X3

      UniProtKB/TrEMBL
      B4DRQ6
      Conserved Domains (2) summary
      TIGR01658
      Location:374 → 645
      EYA-cons_domain; eyes absent protein conserved domain
      pfam12533
      Location:207 → 286
      Neuro_bHLH; Neuronal helix-loop-helix transcription factor

    13. XM_017010369.3 → XP_016865858.1  eyes absent homolog 4 isoform X2

      UniProtKB/TrEMBL
      B4DRQ6

    14. XM_047418281.1 → XP_047274237.1  eyes absent homolog 4 isoform X11

    15. XM_017010371.3 → XP_016865860.1  eyes absent homolog 4 isoform X5

      UniProtKB/TrEMBL
      E7ESD5

    16. XM_047418283.1 → XP_047274239.1  eyes absent homolog 4 isoform X13

    17. XM_047418280.1 → XP_047274236.1  eyes absent homolog 4 isoform X10

    18. XM_047418284.1 → XP_047274240.1  eyes absent homolog 4 isoform X14

    19. XM_017010374.3 → XP_016865863.1  eyes absent homolog 4 isoform X17

      UniProtKB/TrEMBL
      E7ESD5
      Related
      ENSP00000388670.2, ENST00000430974.6

    20. XM_047418287.1 → XP_047274243.1  eyes absent homolog 4 isoform X19

    RNA

    1. XR_001743219.3 RNA Sequence

    2. XR_001743220.3 RNA Sequence

    3. XR_007059221.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      134429416..134720956
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054354458.1 → XP_054210433.1  eyes absent homolog 4 isoform X8

    2. XM_054354459.1 → XP_054210434.1  eyes absent homolog 4 isoform X9

    3. XM_054354469.1 → XP_054210444.1  eyes absent homolog 4 isoform X18

      UniProtKB/TrEMBL
      A0A8C8KDW0

    4. XM_054354471.1 → XP_054210446.1  eyes absent homolog 4 isoform X20

      UniProtKB/TrEMBL
      A0A0S2Z3Q2

    5. XM_054354451.1 → XP_054210426.1  eyes absent homolog 4 isoform X1

    6. XM_054354454.1 → XP_054210429.1  eyes absent homolog 4 isoform X4

    7. XM_054354456.1 → XP_054210431.1  eyes absent homolog 4 isoform X6

    8. XM_054354466.1 → XP_054210441.1  eyes absent homolog 4 isoform X15

    9. XM_054354467.1 → XP_054210442.1  eyes absent homolog 4 isoform X16

    10. XM_054354462.1 → XP_054210437.1  eyes absent homolog 4 isoform X12

      UniProtKB/TrEMBL
      E9PLN6

    11. XM_054354453.1 → XP_054210428.1  eyes absent homolog 4 isoform X3

    12. XM_054354461.1 → XP_054210436.1  eyes absent homolog 4 isoform X11

    13. XM_054354463.1 → XP_054210438.1  eyes absent homolog 4 isoform X13

    14. XM_054354464.1 → XP_054210439.1  eyes absent homolog 4 isoform X14

    15. XM_054354468.1 → XP_054210443.1  eyes absent homolog 4 isoform X17

    16. XM_054354470.1 → XP_054210445.1  eyes absent homolog 4 isoform X19

    17. XM_054354457.1 → XP_054210432.1  eyes absent homolog 4 isoform X7

    18. XM_054354452.1 → XP_054210427.1  eyes absent homolog 4 isoform X2

    19. XM_054354465.1 → XP_054210440.1  eyes absent homolog 4 isoform X21

    20. XM_054354455.1 → XP_054210430.1  eyes absent homolog 4 isoform X5

    21. XM_054354460.1 → XP_054210435.1  eyes absent homolog 4 isoform X10

    RNA

    1. XR_008487274.1 RNA Sequence

    2. XR_008487275.1 RNA Sequence

    3. XR_008487276.1 RNA Sequence

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_172104.1: Suppressed sequence

      Description
      NM_172104.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O95677.2 GenPept UniProtKB/Swiss-Prot:O95677

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    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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