DHFR dihydrofolate reductase [Homo sapiens (human)] - Gene

Summary

Official Symbol: DHFRprovided by HGNC
Official Full Name: dihydrofolate reductaseprovided by HGNC
Primary source: HGNC:HGNC:2861
See related: Ensembl:ENSG00000228716 MIM:126060; AllianceGenome:HGNC:2861
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; DHFR1; 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: mouse all
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Genomic context

Location:: 5q14.1

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (80626226..80654983, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (81111116..81139892, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (79922045..79950802, complement)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Cryo-kinetics Reveal Dynamic Effects on the Chemistry of Human Dihydrofolate Reductase.
Title: Cryo-kinetics Reveal Dynamic Effects on the Chemistry of Human Dihydrofolate Reductase.
Dihydrofolate reductase activity controls neurogenic transitions in the developing neocortex.
Title: Dihydrofolate reductase activity controls neurogenic transitions in the developing neocortex.
Evolutionary adaptation of DHFR via expression of enzyme isoforms with various binding properties and dynamics behavior: a bioinformatics and computational study.
Title: Evolutionary adaptation of DHFR via expression of enzyme isoforms with various binding properties and dynamics behavior: a bioinformatics and computational study.
Evolution of Optimized Hydride Transfer Reaction and Overall Enzyme Turnover in Human Dihydrofolate Reductase.
Title: Evolution of Optimized Hydride Transfer Reaction and Overall Enzyme Turnover in Human Dihydrofolate Reductase.
A comprehensive association analysis between homocysteine metabolic pathway gene methylation and ischemic stroke in a Chinese hypertensive population.
Title: A comprehensive association analysis between homocysteine metabolic pathway gene methylation and ischemic stroke in a Chinese hypertensive population.
Gene Polymorphisms Involved in Folate Metabolism and DNA Methylation with the Risk of Head and Neck Cancer.
Title: Gene Polymorphisms Involved in Folate Metabolism and DNA Methylation with the Risk of Head and Neck Cancer.
Inhibition of DHFR targets the self-renewing potential of brain tumor initiating cells.
Title: Inhibition of DHFR targets the self-renewing potential of brain tumor initiating cells.
Dihydrofolate Reductase (DHFR) del19bp Polymorphism and Down Syndrome Offspring.
Title: Dihydrofolate Reductase (DHFR) del19bp Polymorphism and Down Syndrome Offspring.
Effects of germline DHFR and FPGS variants on methotrexate metabolism and relapse of leukemia.
Title: Effects of germline DHFR and FPGS variants on methotrexate metabolism and relapse of leukemia.
Casein kinase 2 alpha strongly interacts with and phosphorylates dihydrofolate reductase.
Title: Human dihydrofolate reductase is a substrate of protein kinase CK2α.

Submit: New GeneRIF Correction See all GeneRIFs (105)

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
Constitutional megaloblastic anemia with severe neurologic disease MedGen: C3151205 OMIM: 613839 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Genetic variation in the HLA region is associated with susceptibility to herpes zoster. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

WI-18379 (e-PCR)
- UniSTS:23818

GDB:344962 (e-PCR)
- UniSTS:156697

D8S2279 (e-PCR)
- UniSTS:473907

PMC85091P1 (e-PCR)
- UniSTS:273465

PMC316374P5 (e-PCR)
- UniSTS:272966

D15S1477 (e-PCR)
- UniSTS:474482

PMC303366P3 (e-PCR)
- UniSTS:272510

RH70434 (e-PCR)
- UniSTS:89482

STS-AA010576 (e-PCR)
- UniSTS:8636

PMC149466P1 (e-PCR)
- UniSTS:271036

PMC149466P2 (e-PCR)
- UniSTS:271037

PMC149466P3 (e-PCR)
- UniSTS:271038

PMC149466P8 (e-PCR)
- UniSTS:271043

PMC149466P9 (e-PCR)
- UniSTS:271044

PMC89807P1 (e-PCR)
- UniSTS:273613

RH68956 (e-PCR)
- UniSTS:89808

PMC137126P1 (e-PCR)
- UniSTS:270818

RH69621 (e-PCR)
- UniSTS:90851

RH79212 (e-PCR)
- UniSTS:90871

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables NADP binding	IBA Inferred from Biological aspect of Ancestor more info
enables NADPH binding	IDA Inferred from Direct Assay more info	PubMed
enables dihydrofolate reductase activity	IBA Inferred from Biological aspect of Ancestor more info
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 mRNA regulatory element binding translation repressor activity	IDA Inferred from Direct Assay more info	PubMed
enables sequence-specific mRNA 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
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
involved_in folic acid metabolic process	ISS Inferred from Sequence or Structural Similarity 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	IEA Inferred from Electronic Annotation 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
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
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: dihydrofolate reductase

NP_000782.1

EC 1.5.1.3

NP_001277283.1

EC 1.5.1.3

NP_001277286.1

EC 1.5.1.3

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

NG_023304.1 RefSeqGene

Range

4999..33756

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000791.4 → NP_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

B4DDD2, P00374, Q14130, Q6IRW8

UniProtKB/TrEMBL

B0YJ76

Related

ENSP00000396308.2, ENST00000439211.7

Conserved Domains (1) summary

cd00209
Location:5 → 184

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, ...
NM_001290354.2 → NP_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:1 → 132

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, ...
NM_001290357.2 → NP_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, C9JJ68

Related

ENSP00000422732.1, ENST00000511032.5

Conserved Domains (1) summary

cd00209
Location:5 → 128

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

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