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DHFR dihydrofolate reductase [ Homo sapiens (human) ]

Gene ID: 1719, updated on 26-May-2016
Official Symbol
DHFRprovided by HGNC
Official Full Name
dihydrofolate reductaseprovided by HGNC
Primary source
HGNC:HGNC:2861
See related
Ensembl:ENSG00000228716 HPRD:00519; MIM:126060; Vega:OTTHUMG00000162529
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
DYR; DHFRP1
Summary
Dihydrofolate reductase converts dihydrofolate into tetrahydrofolate, a methyl group shuttle required for the de novo synthesis of purines, thymidylic acid, and certain amino acids. While the functional dihydrofolate reductase gene has been mapped to chromosome 5, multiple intronless processed pseudogenes or dihydrofolate reductase-like genes have been identified on separate chromosomes. Dihydrofolate reductase deficiency has been linked to megaloblastic anemia. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]
Orthologs
Location:
5q14.1
Exon count:
6
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 5 NC_000005.10 (80626226..80654981, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (79922045..79950800, complement)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 1337 Neighboring gene diazepam binding inhibitor (GABA receptor modulator, acyl-CoA binding protein) pseudogene 2 Neighboring gene MT-RNR2-like 2 Neighboring gene mutS homolog 3 Neighboring gene S-phase kinase-associated protein 1 pseudogene Neighboring gene ribosomal protein S26 pseudogene 27

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Megaloblastic anemia due to dihydrofolate reductase deficiency
MedGen: C3151205 OMIM: 613839 GeneReviews: Not available
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NHGRI GWAS Catalog

Description
Genetic variation in the HLA region is associated with susceptibility to herpes zoster.
NHGRI GWA Catalog
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
NADPH binding IDA
Inferred from Direct Assay
more info
PubMed 
dihydrofolate reductase activity IDA
Inferred from Direct Assay
more info
PubMed 
dihydrofolate reductase activity ISS
Inferred from Sequence or Structural Similarity
more info
 
dihydrofolate reductase activity NAS
Non-traceable Author Statement
more info
PubMed 
drug binding IDA
Inferred from Direct Assay
more info
PubMed 
folate reductase activity TAS
Traceable Author Statement
more info
 
folic acid binding IDA
Inferred from Direct Assay
more info
PubMed 
mRNA binding IDA
Inferred from Direct Assay
more info
PubMed 
methotrexate binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
G1/S transition of mitotic cell cycle TAS
Traceable Author Statement
more info
 
axon regeneration ISS
Inferred from Sequence or Structural Similarity
more info
 
dihydrofolate metabolic process IDA
Inferred from Direct Assay
more info
PubMed 
folic acid metabolic process ISS
Inferred from Sequence or Structural Similarity
more info
 
folic acid metabolic process TAS
Traceable Author Statement
more info
 
glycine biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
nucleotide biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
one-carbon metabolic process IEA
Inferred from Electronic Annotation
more info
 
oxidation-reduction process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of nitric-oxide synthase activity ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of removal of superoxide radicals ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of transcription involved in G1/S transition of mitotic cell cycle TAS
Traceable Author Statement
more info
 
response to methotrexate ISS
Inferred from Sequence or Structural Similarity
more info
 
tetrahydrobiopterin biosynthetic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
tetrahydrobiopterin biosynthetic process ISS
Inferred from Sequence or Structural Similarity
more info
 
tetrahydrofolate biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
tetrahydrofolate biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
tetrahydrofolate metabolic process IDA
Inferred from Direct Assay
more info
PubMed 
Component Evidence Code Pubs
cellular_component ND
No biological Data available
more info
 
cytosol TAS
Traceable Author Statement
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
Preferred Names
dihydrofolate reductase
NP_000782.1
NP_001277283.1
NP_001277286.1

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_023304.1 RefSeqGene

    Range
    5001..33756
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000791.3NP_000782.1  dihydrofolate reductase isoform 1

    See identical proteins and their annotated locations for NP_000782.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AA489055, AC008434, BC003584, CB988944
    Consensus CDS
    CCDS47240.1
    UniProtKB/Swiss-Prot
    P00374
    UniProtKB/TrEMBL
    B0YJ76
    Related
    ENSP00000396308, OTTHUMP00000222282, ENST00000439211, OTTHUMT00000369450
    Conserved Domains (1) summary
    cd00209
    Location:5184
    DHFR; Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with NADPH as a cofactor. This is an essential step in the biosynthesis of deoxythymidine phosphate since 5,6,7,8-tetrahydrofolate is required to regenerate 5, ...
  2. NM_001290354.1NP_001277283.1  dihydrofolate reductase isoform 2

    See identical proteins and their annotated locations for NP_001277283.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate exon in the 5' end compared to variant 1. This difference causes translation initiation at a downstream AUG and results in an isoform (2) with a shorter N-terminus compared to isoform 1.
    Source sequence(s)
    AA489055, AC008434, AC010270, AK293146
    Consensus CDS
    CCDS78028.1
    UniProtKB/Swiss-Prot
    P00374
    Related
    ENSP00000421334, OTTHUMP00000222283, ENST00000504396, OTTHUMT00000369452
    Conserved Domains (1) summary
    cd00209
    Location:1132
    DHFR; Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with NADPH as a cofactor. This is an essential step in the biosynthesis of deoxythymidine phosphate since 5,6,7,8-tetrahydrofolate is required to regenerate 5, ...
  3. NM_001290357.1NP_001277286.1  dihydrofolate reductase isoform 3

    See identical proteins and their annotated locations for NP_001277286.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate exon in the 3' end compared to variant 1, that causes a frameshift. The resulting isoform (3) has a shorter and distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AA489055, AC008434, AC010270, AK297302
    Consensus CDS
    CCDS78029.1
    UniProtKB/TrEMBL
    B4DM58
    Related
    ENSP00000422732, OTTHUMP00000222285, ENST00000511032, OTTHUMT00000369454
    Conserved Domains (1) summary
    cd00209
    Location:5128
    DHFR; Dihydrofolate reductase (DHFR). Reduces 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate with NADPH as a cofactor. This is an essential step in the biosynthesis of deoxythymidine phosphate since 5,6,7,8-tetrahydrofolate is required to regenerate 5, ...

RNA

  1. NR_110936.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks two alternate exons compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AA489055, AC008434, AC010270, AK308492

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107 details...

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

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p2 Primary Assembly

    Range
    80626226..80654981 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018916.2 Alternate CHM1_1.1

    Range
    79355281..79384046 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)