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NDUFAF6 NADH:ubiquinone oxidoreductase complex assembly factor 6 [ Homo sapiens (human) ]

Gene ID: 137682, updated on 5-Mar-2024

Summary

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Official Symbol
NDUFAF6provided by HGNC
Official Full Name
NADH:ubiquinone oxidoreductase complex assembly factor 6provided by HGNC
Primary source
HGNC:HGNC:28625
See related
Ensembl:ENSG00000156170 MIM:612392; AllianceGenome:HGNC:28625
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
FRTS5; C8orf38; MC1DN17
Summary
This gene encodes a protein that localizes to mitochondria and contains a predicted phytoene synthase domain. The encoded protein plays an important role in the assembly of complex I (NADH-ubiquinone oxidoreductase) of the mitochondrial respiratory chain through regulation of subunit ND1 biogenesis. Mutations in this gene are associated with complex I enzymatic deficiency. [provided by RefSeq, Nov 2011]
Expression
Ubiquitous expression in thyroid (RPKM 1.4), testis (RPKM 1.4) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
8q22.1
Exon count:
27
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (94895799..95118496)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (96020781..96243737)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (95908027..96130724)

Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19369 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27635 Neighboring gene integrator complex subunit 8 Neighboring gene ribosomal protein L17 pseudogene Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr8:95906241-95906802 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19370 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19371 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19372 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19373 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19374 Neighboring gene small nucleolar RNA U13 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27636 Neighboring gene cyclin E2 Neighboring gene tumor protein p53 inducible nuclear protein 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancers GRCh37_chr8:95960947-95961575 and GRCh37_chr8:95961576-95962205 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27638 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27639 Neighboring gene ReSE screen-validated silencer GRCh37_chr8:95974156-95974312 Neighboring gene NANOG hESC enhancer GRCh37_chr8:95987500-95988063 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:96036276-96037122 Neighboring gene Sharpr-MPRA regulatory region 2014 Neighboring gene uncharacterized LOC124901981 Neighboring gene RNA, U6 small nuclear 1209, pseudogene Neighboring gene uncharacterized LOC124901980 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19379 Neighboring gene MIR3150B host gene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27640 Neighboring gene microRNA 3150b Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27641 Neighboring gene microRNA 3150a Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27642 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27643 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27644 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27645 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19380 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27646 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27647 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19381 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19382 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27648 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19383 Neighboring gene uncharacterized LOC124901982 Neighboring gene pleckstrin homology and FYVE domain containing 2 Neighboring gene CRISPRi-validated cis-regulatory element chr8.2347 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19384 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27649 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27650

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. Genetic Effects of NDUFAF6 rs6982393 and APOE on Alzheimer's Disease in Chinese Rural Elderly: A Cross-Sectional Population-Based Study. Cheng Y, et al. Clin Interv Aging, 2022. PMID 35237031, Free PMC Article
  2. Mutations in the mitochondrial complex I assembly factor NDUFAF6 cause isolated bilateral striatal necrosis and progressive dystonia in childhood. Baide-Mairena H, et al. Mol Genet Metab, 2019 Mar. PMID 30642748
  3. Evolution, structure and membrane association of NDUFAF6, an assembly factor for NADH:ubiquinone oxidoreductase (Complex I). Lemire BD. Mitochondrion, 2017 Jul. PMID 28476317
  4. Exome sequencing coupled with mRNA analysis identifies NDUFAF6 as a Leigh gene. Bianciardi L, et al. Mol Genet Metab, 2016 Nov. PMID 27623250
  5. Acadian variant of Fanconi syndrome is caused by mitochondrial respiratory chain complex I deficiency due to a non-coding mutation in complex I assembly factor NDUFAF6. Hartmannová H, et al. Hum Mol Genet, 2016 Sep 15. PMID 27466185

See all (25) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Genetic Effects of NDUFAF6 rs6982393 and APOE on Alzheimer's Disease in Chinese Rural Elderly: A Cross-Sectional Population-Based Study.
    Title: Genetic Effects of NDUFAF6 rs6982393 and APOE on Alzheimer's Disease in Chinese Rural Elderly: A Cross-Sectional Population-Based Study.
  2. NDUFAF6-related Leigh syndrome is a relevant cause of childhood onset dystonia and isolated bilateral striatal necrosis [review]
    Title: Mutations in the mitochondrial complex I assembly factor NDUFAF6 cause isolated bilateral striatal necrosis and progressive dystonia in childhood.
  3. NDUFAF6 encodes a complex I assembly factor and mutations result in complex I deficiency, Leigh syndrome or Acadian variant Fanconi syndrome. Human NDUFAF6 is a mitochondria-targeted 333-amino acid protein belonging to the family of squalene and phytoene synthases.
    Title: Evolution, structure and membrane association of NDUFAF6, an assembly factor for NADH:ubiquinone oxidoreductase (Complex I).
  4. This paper confirms NDUFAF6 as a genuine morbid gene and proposes the coupling of exome sequencing with mRNA analysis as a method useful for enhancing the exome sequencing detection rate when the simple application of classical inheritance models fails.
    Title: Exome sequencing coupled with mRNA analysis identifies NDUFAF6 as a Leigh gene.
  5. Affected kidney and lung showed specific loss of the mitochondria-located NDUFAF6 isoform and ultrastructural characteristics of mitochondrial dysfunction. Accordingly, affected tissues had defects in mitochondrial respiration and complex I biogenesis that were corrected with NDUFAF6 cDNA transfection. Our results demonstrate that the Acadian variant of Fanconi Syndrome results from mitochondrial respiratory chain complex
    Title: Acadian variant of Fanconi syndrome is caused by mitochondrial respiratory chain complex I deficiency due to a non-coding mutation in complex I assembly factor NDUFAF6.
  6. In a forward genetic screen to identify genes that cause neurodegeneration, we identified sicily, the Drosophila melanogaster homologue of human C8ORF38, the loss of which causes Leigh syndrome.
    Title: The C8ORF38 homologue Sicily is a cytosolic chaperone for a mitochondrial complex I subunit.
  7. C8orf38 is a crucial factor required for the translation and/or integration of ND1 into an early-stage assembly intermediate
    Title: Mutations in the gene encoding C8orf38 block complex I assembly by inhibiting production of the mitochondria-encoded subunit ND1.
  8. Observational study of gene-disease association. (HuGE Navigator)
    Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
Submit: New GeneRIF Correction

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

Associated conditions

Description Tests
Fanconi renotubular syndrome 5
MedGen: C5394473 OMIM: 618913 GeneReviews: Not available
Compare labs
Mitochondrial complex 1 deficiency, nuclear type 17
MedGen: C4748786 OMIM: 618239 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.
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)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC40214

Gene Ontology Provided by GOA

Process Evidence Code Pubs
involved_in biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in mitochondrial respiratory chain complex I assembly IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in mitochondrial respiratory chain complex I assembly IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in mitochondrial inner membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrial inner membrane TAS
Traceable Author Statement
more info
  
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
NADH dehydrogenase (ubiquinone) complex I, assembly factor 6
Names
UPF0551 protein C8orf38, mitochondrial
putative phytoene synthase

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_016647.2 RefSeqGene

    Range
    134719..168440
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001330582.2 → NP_001317511.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2), as well as variants 3 and 4, encodes isoform 2.
    Source sequence(s)
    AA625387, AC068189, BX282282, CN344829, HY013350
    Consensus CDS
    CCDS83307.1
    UniProtKB/TrEMBL
    A0A075B6P0
    Conserved Domains (1) summary
    pfam00494
    Location:8 → 219
    SQS_PSY; Squalene/phytoene synthase

  2. NM_001354514.2 → NP_001341443.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3), as well as variants 2 and 4, encodes isoform 2.
    Source sequence(s)
    AC068189, AC087752
    Consensus CDS
    CCDS83307.1
    UniProtKB/TrEMBL
    A0A075B6P0
    Related
    ENSP00000513278.1, ENST00000697364.1
    Conserved Domains (1) summary
    pfam00494
    Location:8 → 219
    SQS_PSY; Squalene/phytoene synthase

  3. NM_001354515.2 → NP_001341444.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4), as well as variants 2 and 3, encodes isoform 2.
    Source sequence(s)
    AC068189, AC087752
    Consensus CDS
    CCDS83307.1
    UniProtKB/TrEMBL
    A0A075B6P0
    Related
    ENSP00000379417.1, ENST00000396111.6
    Conserved Domains (1) summary
    pfam00494
    Location:8 → 219
    SQS_PSY; Squalene/phytoene synthase

  4. NM_001354516.2 → NP_001341445.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC068189, AC087752
    Conserved Domains (1) summary
    pfam00494
    Location:14 → 259
    SQS_PSY; Squalene/phytoene synthase

  5. NM_001354517.2 → NP_001341446.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6), as well as variants 7 and 8, encodes isoform 4.
    Source sequence(s)
    AC068189
    Conserved Domains (1) summary
    pfam00494
    Location:1 → 200
    SQS_PSY; Squalene/phytoene synthase

  6. NM_001354518.2 → NP_001341447.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7), as well as variants 6 and 8, encodes isoform 4.
    Source sequence(s)
    AC068189
    Conserved Domains (1) summary
    pfam00494
    Location:1 → 200
    SQS_PSY; Squalene/phytoene synthase

  7. NM_001354519.2 → NP_001341448.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8), as well as variants 6 and 7, encodes isoform 4.
    Source sequence(s)
    AC068189
    Conserved Domains (1) summary
    pfam00494
    Location:1 → 200
    SQS_PSY; Squalene/phytoene synthase

  8. NM_001354521.2 → NP_001341450.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 5

    Status: REVIEWED

    Source sequence(s)
    AC068189
    Conserved Domains (1) summary
    cl00210
    Location:8 → 200
    Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

  9. NM_001354522.2 → NP_001341451.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (10), as well as variants 11-19, encodes isoform 6.
    Source sequence(s)
    AC068189, AC087752
    Conserved Domains (1) summary
    cl00210
    Location:1 → 159
    Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

  10. NM_001354524.2 → NP_001341453.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (11), as well as variants 10 and 12-19, encodes isoform 6.
    Source sequence(s)
    AC068189, AC087752
    Conserved Domains (1) summary
    cl00210
    Location:1 → 159
    Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

  11. NM_001354525.2 → NP_001341454.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (12), as well as variants 10, 11, and 13-19, encodes isoform 6.
    Source sequence(s)
    AC068189, AC087752
    Conserved Domains (1) summary
    cl00210
    Location:1 → 159
    Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

  12. NM_001354527.2 → NP_001341456.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (13), as well as variants 10-12 and 14-19, encodes isoform 6.
    Source sequence(s)
    AC068189, BC028166
    Conserved Domains (1) summary
    cl00210
    Location:1 → 159
    Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

  13. NM_001354528.2 → NP_001341457.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (14), as well as variants 10-13 and 15-19, encodes isoform 6.
    Source sequence(s)
    AC068189
    Conserved Domains (1) summary
    cl00210
    Location:1 → 159
    Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

  14. NM_001354529.2 → NP_001341458.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (15), as well as variants 10-14 and 16-19, encodes isoform 6.
    Source sequence(s)
    AC068189
    Conserved Domains (1) summary
    cl00210
    Location:1 → 159
    Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

  15. NM_001354530.2 → NP_001341459.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (16), as well as variants 10-15 and 17-19, encodes isoform 6.
    Source sequence(s)
    AC068189
    Conserved Domains (1) summary
    cl00210
    Location:1 → 159
    Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

  16. NM_001354531.2 → NP_001341460.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (17), as well as variants 10-16, 18, and 19, encodes isoform 6.
    Source sequence(s)
    AC068189
    Conserved Domains (1) summary
    cl00210
    Location:1 → 159
    Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

  17. NM_001354532.2 → NP_001341461.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (18), as well as variants 10-17 and 19, encodes isoform 6.
    Source sequence(s)
    AC068189
    Conserved Domains (1) summary
    cl00210
    Location:1 → 159
    Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

  18. NM_001354533.2 → NP_001341462.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (19), as well as variants 10-18, encodes isoform 6.
    Source sequence(s)
    AC068189
    Conserved Domains (1) summary
    cl00210
    Location:1 → 159
    Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

  19. NM_001354534.2 → NP_001341463.1  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 7

    Status: REVIEWED

    Source sequence(s)
    AC068189, AC087752
    Conserved Domains (1) summary
    cl00210
    Location:1 → 159
    Isoprenoid_Biosyn_C1; Isoprenoid Biosynthesis enzymes, Class 1

  20. NM_152416.4 → NP_689629.2  NADH dehydrogenase (ubiquinone) complex I, assembly factor 6 isoform 1 precursor

    See identical proteins and their annotated locations for NP_689629.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AA489642, AK298631, BF030925, BM755491, DA897677
    Consensus CDS
    CCDS6266.2
    UniProtKB/Swiss-Prot
    A8MT28, A8MWF0, B4DQ45, Q330K2, Q8N6U6
    Related
    ENSP00000379430.4, ENST00000396124.9
    Conserved Domains (1) summary
    pfam00494
    Location:65 → 311
    SQS_PSY; Squalene/phytoene synthase

RNA

  1. NR_148903.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC087752

  2. NR_148904.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC087752

  3. NR_148905.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC087752
    Related
    ENST00000697356.1

  4. NR_148906.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC087752

  5. NR_148907.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC087752

  6. NR_148908.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC087752
    Related
    ENST00000697359.1

  7. NR_148909.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC087752

  8. NR_148910.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC068189

  9. NR_148911.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC068189

  10. NR_148912.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC068189

  11. NR_148913.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC018801, AC068189

  12. NR_148914.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC018801, AC068189

  13. NR_148915.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC068189, AK301414

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000008.11 Reference GRCh38.p14 Primary Assembly

    Range
    94895799..95118496
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060932.1 Alternate T2T-CHM13v2.0

    Range
    96020781..96243737
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q330K2.2 GenPept UniProtKB/Swiss-Prot:Q330K2

Gene LinkOut

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Chemical Information
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