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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
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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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