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ALDH1L1 aldehyde dehydrogenase 1 family member L1 [ Homo sapiens (human) ]

Gene ID: 10840, updated on 7-Apr-2024

Summary

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Official Symbol
ALDH1L1provided by HGNC
Official Full Name
aldehyde dehydrogenase 1 family member L1provided by HGNC
Primary source
HGNC:HGNC:3978
See related
Ensembl:ENSG00000144908 MIM:600249; AllianceGenome:HGNC:3978
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
FDH; FTHFD; 10-fTHF; 10-FTHFDH
Summary
The protein encoded by this gene catalyzes the conversion of 10-formyltetrahydrofolate, nicotinamide adenine dinucleotide phosphate (NADP+), and water to tetrahydrofolate, NADPH, and carbon dioxide. The encoded protein belongs to the aldehyde dehydrogenase family. Loss of function or expression of this gene is associated with decreased apoptosis, increased cell motility, and cancer progression. There is an antisense transcript that overlaps on the opposite strand with this gene locus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]
Expression
Biased expression in liver (RPKM 99.3), kidney (RPKM 65.2) and 8 other tissues See more
Orthologs
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Genomic context

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Location:
3q21.3
Exon count:
27
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (126103570..126197945, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (128835963..128930120, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (125822413..125900029, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene solute carrier family 41 member 3 Neighboring gene uncharacterized LOC124909425 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125777675-125778174 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14672 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14673 Neighboring gene ALDH1L1 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20435 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20436 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125822083-125822904 Neighboring gene ALDH1L1 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125831607-125832121 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125847779-125848549 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125850681-125851498 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14674 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125855703-125856203 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_64577 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125876969-125877469 Neighboring gene uncharacterized LOC105374083 Neighboring gene RNA, U1 small nuclear 30, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125899089-125899844 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125899845-125900598 Neighboring gene Sharpr-MPRA regulatory region 2719 Neighboring gene ALDH1L1 antisense RNA 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20437 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr3:125926972-125928171 Neighboring gene uncharacterized LOC124909426 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125932350-125932862 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:125977069-125977976 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:125985551-125986260 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:125986261-125986971 Neighboring gene uncharacterized LOC107986124 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:126006839-126007384 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:126007385-126007929 Neighboring gene KLF transcription factor 15

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. Abnormal downregulation of 10-formyltetrahydrofolate dehydrogenase promotes the progression of oral squamous cell carcinoma by activating PI3K/Akt/Rb pathway. Qu Y, et al. Cancer Med, 2023 Mar. PMID 36336972, Free PMC Article
  2. Modeling of interactions between functional domains of ALDH1L1. Horita DA, et al. Chem Biol Interact, 2017 Oct 1. PMID 28414156, Free PMC Article
  3. Aldehyde dehydrogenase inhibition combined with phenformin treatment reversed NSCLC through ATP depletion. Kang JH, et al. Oncotarget, 2016 Aug 2. PMID 27384481, Free PMC Article
  4. Association between ALDH1L1 gene polymorphism and neural tube defects in the Chinese Han population. Wu L, et al. Neurol Sci, 2016 Jul. PMID 26993122
  5. Division of labour: how does folate metabolism partition between one-carbon metabolism and amino acid oxidation? Brosnan ME, et al. Biochem J, 2015 Dec 1. PMID 26567272

See all (78) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. One-carbon metabolizing enzyme ALDH1L1 influences mitochondrial metabolism through 5-aminoimidazole-4-carboxamide ribonucleotide accumulation and serine depletion, contributing to tumor suppression.
    Title: One-carbon metabolizing enzyme ALDH1L1 influences mitochondrial metabolism through 5-aminoimidazole-4-carboxamide ribonucleotide accumulation and serine depletion, contributing to tumor suppression.
  2. Abnormal downregulation of 10-formyltetrahydrofolate dehydrogenase promotes the progression of oral squamous cell carcinoma by activating PI3K/Akt/Rb pathway.
    Title: Abnormal downregulation of 10-formyltetrahydrofolate dehydrogenase promotes the progression of oral squamous cell carcinoma by activating PI3K/Akt/Rb pathway.
  3. Genetic variants in ALDH1L1 and GLDC influence the serine-to-glycine ratio in Hispanic children.
    Title: Genetic variants in ALDH1L1 and GLDC influence the serine-to-glycine ratio in Hispanic children.
  4. [Functional Hypermethylation of ALDH1L1, PLCL2, and PPP2R3A in Colon Cancer].
    Title: [Functional Hypermethylation of ALDH1L1, PLCL2, and PPP2R3A in Colon Cancer].
  5. Our results suggest that ALDH1L1 may be a biomarker for predicting postoperative clinical outcomes. Moreover, ALDH1L1-rs2276724 and mRNA expression were associated with TP53 expression in HBV-related hepatocellular carcinoma patients
    Title: ALDH1L1 variant rs2276724 and mRNA expression predict post-operative clinical outcomes and are associated with TP53 expression in HBV-related hepatocellular carcinoma.
  6. ALDH1L1 has a role in response to the combined treatment of gossypol and phenformin in non-small cell lung cancer
    Title: Aldehyde dehydrogenase inhibition combined with phenformin treatment reversed NSCLC through ATP depletion.
  7. high transcription activities of ALDH1A2, ALDH1A3 and ALDH1L1 predicted worsen overall survival in gastric cancer patients
    Title: Mining distinct aldehyde dehydrogenase 1 (ALDH1) isoenzymes in gastric cancer.
  8. The three functional domains of ALDH1L1 was defined positions of the 4'-phosphopantetheine arm within the two catalytic domains and to predict N-terminal:intermediate and intermediate:C-terminal domain interfaces.
    Title: Modeling of interactions between functional domains of ALDH1L1.
  9. The polymorphic loci rs4646733, rs2305225, and rs2276731 in the ALDH1L1 gene maybe potential risk factors for neural tube defects in the Chinese population.
    Title: Association between ALDH1L1 gene polymorphism and neural tube defects in the Chinese Han population.
  10. Data suggest that isoforms of FTHFD occur both in mitochondria and in cytosol; activity of cytosolic FTHFD appears to respond to supply of one-carbon groups in excess of those required for classical one-carbon metabolism. [REVIEW]
    Title: Division of labour: how does folate metabolism partition between one-carbon metabolism and amino acid oxidation?
Submit: New GeneRIF Correction See all GeneRIFs (25)

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

EBI GWAS Catalog

Description
Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes.
EBI GWAS Catalog
Genome wide association study (GWAS) of Chagas cardiomyopathy in Trypanosoma cruzi seropositive subjects.
EBI GWAS Catalog
Genome-wide meta-analysis of homocysteine and methionine metabolism identifies five one carbon metabolism loci and a novel association of ALDH1L1 with ischemic stroke.
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

  • DKFZp781N0997

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables aldehyde dehydrogenase (NAD+) activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables formyltetrahydrofolate dehydrogenase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables formyltetrahydrofolate dehydrogenase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables formyltetrahydrofolate dehydrogenase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
Process Evidence Code Pubs
involved_in 10-formyltetrahydrofolate catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in 10-formyltetrahydrofolate catabolic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in NADPH regeneration IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in one-carbon metabolic process IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 

General protein information

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Preferred Names
cytosolic 10-formyltetrahydrofolate dehydrogenase
Names
10-formyltetrahydrofolate dehydrogenase
MER57B-ALDH1L1
NP_001257293.1
NP_001257294.1
NP_036322.2
XP_006713544.1
XP_011510657.1
XP_016861102.1
XP_016861103.1
XP_024309093.1
XP_054201003.1
XP_054201004.1
XP_054201005.1
XP_054201006.1
XP_054201007.1

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_012260.2 RefSeqGene

    Range
    22359..99375
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001270364.2 → NP_001257293.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform 1

    See identical proteins and their annotated locations for NP_001257293.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest protein (isoform 1).
    Source sequence(s)
    AC079848
    Consensus CDS
    CCDS58851.1
    UniProtKB/TrEMBL
    Q53H87
    Related
    ENSP00000273450.3, ENST00000273450.7
    Conserved Domains (5) summary
    cd07140
    Location:427 → 912
    ALDH_F1L_FTFDH; 10-formyltetrahydrofolate dehydrogenase, ALDH family 1L
    cd08647
    Location:11 → 213
    FMT_core_FDH_N; 10-formyltetrahydrofolate dehydrogenase (FDH), N-terminal hydrolase domain
    cd08703
    Location:216 → 316
    FDH_Hydrolase_C; The C-terminal subdomain of the hydrolase domain on the bi-functional protein 10-formyltetrahydrofolate dehydrogenase
    COG0223
    Location:10 → 319
    Fmt; Methionyl-tRNA formyltransferase [Translation, ribosomal structure and biogenesis]
    pfam00550
    Location:335 → 401
    PP-binding; Phosphopantetheine attachment site

  2. NM_001270365.2 → NP_001257294.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the both the 5' UTR and the coding sequence, but maintains the reading frame, compared to variant 1. The resulting isoform (3) is shorter than isoform 1.
    Source sequence(s)
    AC079848, AK222694, AK294392
    Consensus CDS
    CCDS58850.1
    UniProtKB/TrEMBL
    Q53H87
    Related
    ENSP00000395881.2, ENST00000452905.6
    Conserved Domains (4) summary
    cd07140
    Location:316 → 801
    ALDH_F1L_FTFDH; 10-formyltetrahydrofolate dehydrogenase, ALDH family 1L
    cd08703
    Location:116 → 205
    FDH_Hydrolase_C; The C-terminal subdomain of the hydrolase domain on the bi-functional protein 10-formyltetrahydrofolate dehydrogenase
    pfam00550
    Location:224 → 290
    PP-binding; Phosphopantetheine attachment site
    cl00395
    Location:1 → 128
    FMT_core; Formyltransferase, catalytic core domain

  3. NM_012190.4 → NP_036322.2  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform 2

    See identical proteins and their annotated locations for NP_036322.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains a distinct 5' UTR, lacks an in-frame portion of the 5' coding region, and initiates translation at an alternate in-frame downstream start codon, compared to variant 1. The resulting isoform (2) has a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AC079848, AF052732, AK222694, DC342268
    Consensus CDS
    CCDS3034.1
    UniProtKB/Swiss-Prot
    B4DG36, E9PBX3, O75891, Q68CS1, Q8TBP8
    UniProtKB/TrEMBL
    Q53H87
    Related
    ENSP00000377083.3, ENST00000393434.7
    Conserved Domains (4) summary
    cd07140
    Location:417 → 902
    ALDH_F1L_FTFDH; 10-formyltetrahydrofolate dehydrogenase, ALDH family 1L
    cd08647
    Location:1 → 203
    FMT_core_FDH_N; 10-formyltetrahydrofolate dehydrogenase (FDH), N-terminal hydrolase domain
    cd08703
    Location:206 → 306
    FDH_Hydrolase_C; The C-terminal subdomain of the hydrolase domain on the bi-functional protein 10-formyltetrahydrofolate dehydrogenase
    pfam00550
    Location:325 → 391
    PP-binding; Phosphopantetheine attachment site

RNA

  1. NR_072979.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks two internal exons, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AK222694, BC027241, DC342268
    Related
    ENST00000393431.6

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_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    126103570..126197945 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024453325.2 → XP_024309093.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X1

    UniProtKB/Swiss-Prot
    B4DG36, E9PBX3, O75891, Q68CS1, Q8TBP8
    UniProtKB/TrEMBL
    Q53H87
    Conserved Domains (4) summary
    cd07140
    Location:417 → 902
    ALDH_F1L_FTFDH; 10-formyltetrahydrofolate dehydrogenase, ALDH family 1L
    cd08647
    Location:1 → 203
    FMT_core_FDH_N; 10-formyltetrahydrofolate dehydrogenase (FDH), N-terminal hydrolase domain
    cd08703
    Location:206 → 306
    FDH_Hydrolase_C; The C-terminal subdomain of the hydrolase domain on the bi-functional protein 10-formyltetrahydrofolate dehydrogenase
    pfam00550
    Location:325 → 391
    PP-binding; Phosphopantetheine attachment site

  2. XM_011512355.2 → XP_011510657.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X1

    See identical proteins and their annotated locations for XP_011510657.1

    UniProtKB/Swiss-Prot
    B4DG36, E9PBX3, O75891, Q68CS1, Q8TBP8
    UniProtKB/TrEMBL
    Q53H87
    Related
    ENSP00000420293.1, ENST00000472186.5
    Conserved Domains (4) summary
    cd07140
    Location:417 → 902
    ALDH_F1L_FTFDH; 10-formyltetrahydrofolate dehydrogenase, ALDH family 1L
    cd08647
    Location:1 → 203
    FMT_core_FDH_N; 10-formyltetrahydrofolate dehydrogenase (FDH), N-terminal hydrolase domain
    cd08703
    Location:206 → 306
    FDH_Hydrolase_C; The C-terminal subdomain of the hydrolase domain on the bi-functional protein 10-formyltetrahydrofolate dehydrogenase
    pfam00550
    Location:325 → 391
    PP-binding; Phosphopantetheine attachment site

  3. XM_017005613.3 → XP_016861102.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X2

    UniProtKB/TrEMBL
    Q53H87

  4. XM_006713481.4 → XP_006713544.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X1

    See identical proteins and their annotated locations for XP_006713544.1

    UniProtKB/Swiss-Prot
    B4DG36, E9PBX3, O75891, Q68CS1, Q8TBP8
    UniProtKB/TrEMBL
    Q53H87
    Conserved Domains (4) summary
    cd07140
    Location:417 → 902
    ALDH_F1L_FTFDH; 10-formyltetrahydrofolate dehydrogenase, ALDH family 1L
    cd08647
    Location:1 → 203
    FMT_core_FDH_N; 10-formyltetrahydrofolate dehydrogenase (FDH), N-terminal hydrolase domain
    cd08703
    Location:206 → 306
    FDH_Hydrolase_C; The C-terminal subdomain of the hydrolase domain on the bi-functional protein 10-formyltetrahydrofolate dehydrogenase
    pfam00550
    Location:325 → 391
    PP-binding; Phosphopantetheine attachment site

  5. XM_017005614.3 → XP_016861103.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X3

    UniProtKB/TrEMBL
    Q53H87

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    128835963..128930120 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054345030.1 → XP_054201005.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X1

    UniProtKB/Swiss-Prot
    B4DG36, E9PBX3, O75891, Q68CS1, Q8TBP8

  2. XM_054345029.1 → XP_054201004.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X1

    UniProtKB/Swiss-Prot
    B4DG36, E9PBX3, O75891, Q68CS1, Q8TBP8

  3. XM_054345031.1 → XP_054201006.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X2

  4. XM_054345028.1 → XP_054201003.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X1

    UniProtKB/Swiss-Prot
    B4DG36, E9PBX3, O75891, Q68CS1, Q8TBP8

  5. XM_054345032.1 → XP_054201007.1  cytosolic 10-formyltetrahydrofolate dehydrogenase isoform X3

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_144776.1: Suppressed sequence

    Description
    NM_144776.1: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O75891.2 GenPept UniProtKB/Swiss-Prot:O75891

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