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DHFR dihydrofolate reductase [ Homo sapiens (human) ]

Gene ID: 1719, updated on 6-Sep-2021

Summary

Official Symbol
DHFRprovided by HGNC
Official Full Name
dihydrofolate reductaseprovided by HGNC
Primary source
HGNC:HGNC:2861
See related
Ensembl:ENSG00000228716 MIM:126060
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]
Expression
Ubiquitous expression in fat (RPKM 21.2), lymph node (RPKM 18.2) and 24 other tissues See more
Orthologs
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Genomic context

See DHFR in Genome Data Viewer
Location:
5q14.1
Exon count:
6
Annotation release Status Assembly Chr Location
109.20210514 current GRCh38.p13 (GCF_000001405.39) 5 NC_000005.10 (80626226..80654983, complement)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (79922045..79950802, complement)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 1337 Neighboring gene DBI pseudogene 2 Neighboring gene Sharpr-MPRA regulatory region 2279 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

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Genetic variation in the HLA region is associated with susceptibility to herpes zoster.
GeneReviews: Not available
Megaloblastic anemia due to dihydrofolate reductase deficiency
MedGen: C3151205 OMIM: 613839 GeneReviews: Not available
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Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables NADP binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
enables NADPH binding IDA
Inferred from Direct Assay
more info
PubMed 
enables dihydrofolate reductase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
enables dihydrofolate reductase activity IDA
Inferred from Direct Assay
more info
PubMed 
enables dihydrofolate reductase activity ISS
Inferred from Sequence or Structural Similarity
more info
 
enables dihydrofolate reductase activity NAS
Non-traceable Author Statement
more info
PubMed 
enables folic acid binding IDA
Inferred from Direct Assay
more info
PubMed 
enables mRNA binding IDA
Inferred from Direct Assay
more info
PubMed 
enables methotrexate binding IDA
Inferred from Direct Assay
more info
PubMed 
enables sequence-specific mRNA binding IDA
Inferred from Direct Assay
more info
PubMed 
enables translation repressor activity, mRNA regulatory element binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
involved_in axon regeneration ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in dihydrofolate metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in dihydrofolate metabolic process IDA
Inferred from Direct Assay
more info
PubMed 
involved_in folic acid metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in folic acid metabolic process ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in glycine biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
involved_in negative regulation of translation IDA
Inferred from Direct Assay
more info
PubMed 
involved_in one-carbon metabolic process IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of nitric-oxide synthase activity ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in regulation of removal of superoxide radicals ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in response to methotrexate ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in tetrahydrobiopterin biosynthetic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in tetrahydrobiopterin biosynthetic process ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in tetrahydrofolate biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in tetrahydrofolate biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
involved_in tetrahydrofolate biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
involved_in tetrahydrofolate metabolic process IDA
Inferred from Direct Assay
more info
PubMed 
Component Evidence Code Pubs
located_in cytosol TAS
Traceable Author Statement
more info
 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
located_in mitochondrion IDA
Inferred from Direct Assay
more info
 

General protein information

Preferred Names
dihydrofolate reductase
NP_000782.1
NP_001277283.1
NP_001277286.1

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_023304.1 RefSeqGene

    Range
    4999..33756
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000791.4NP_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, AC010270, BC003584, CB988944
    Consensus CDS
    CCDS47240.1
    UniProtKB/Swiss-Prot
    P00374
    UniProtKB/TrEMBL
    B0YJ76
    Related
    ENSP00000396308.2, ENST00000439211.7
    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_001290354.2NP_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
    ENSP00000421334.1, ENST00000504396.1
    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_001290357.2NP_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
    ENSP00000422732.1, ENST00000511032.5
    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_110936.2 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 Updated Annotation Release 109.20210514

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p13 Primary Assembly

    Range
    80626226..80654983 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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