Details for: ADHFE1

Gene ID: 137872

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ADHFE1

Ensembl ID: ENSG00000147576

Description: alcohol dehydrogenase iron containing 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • parietal epithelial cell CL1000452
    CSI 9.39
    rCSI 25.1%
    PRS 91.54
  • alveolar adventitial fibroblast CL4028006
    CSI 9.23
    rCSI 14.57%
    PRS 95.6
  • hepatocyte CL0000182
    CSI 7.11
    rCSI 12.72%
    PRS 93.28
  • pulmonary alveolar type 2 cell CL0002063
    CSI 6.1
    rCSI 9.47%
    PRS 95.14
  • kidney connecting tubule epithelial cell CL1000768
    CSI 5.77
    rCSI 14.64%
    PRS 91.22
  • retinal pigment epithelial cell CL0002586
    CSI 5.12
    rCSI 10.17%
    PRS 92.37
  • cardiac muscle cell CL0000746
    CSI 5.07
    rCSI 7.28%
    PRS 88.79
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 4.14
    rCSI 9.43%
    PRS 88.89
  • Mueller cell CL0000636
    CSI 4.04
    rCSI 9.22%
    PRS 90.41
  • mucosal invariant T cell CL0000940
    CSI 4.01
    rCSI 3.24%
    PRS 97.52
  • syncytiotrophoblast cell CL0000525
    CSI 3.86
    rCSI 11.13%
    PRS 94.67
  • midzonal region hepatocyte CL0019028
    CSI 3.75
    rCSI 8.8%
    PRS 91.87
  • mesothelial cell CL0000077
    CSI 3.45
    rCSI 13.49%
    PRS 83.72
  • alveolar type 1 fibroblast cell CL4028004
    CSI 3.29
    rCSI 3.61%
    PRS 95.81
  • choroid plexus epithelial cell CL0000706
    CSI 3.06
    rCSI 5.02%
    PRS 90.05
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.05
    rCSI 3.79%
    PRS 84.23
  • hepatic stellate cell CL0000632
    CSI 2.95
    rCSI 11.05%
    PRS 92.37
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.88
    rCSI 6.45%
    PRS 86.38
  • vascular leptomeningeal cell CL4023051
    CSI 2.65
    rCSI 4.64%
    PRS 92.91
  • adipocyte CL0000136
    CSI 2.6
    rCSI 3.34%
    PRS 88.8
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 2.59
    rCSI 6.7%
    PRS 93.2
  • lung secretory cell CL1000272
    CSI 2.34
    rCSI 5.8%
    PRS 96.03
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.33
    rCSI 3.3%
    PRS 93.48
  • adventitial cell CL0002503
    CSI 2.13
    rCSI 5.08%
    PRS 96.42
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.04
    rCSI 2.44%
    PRS 86.3
  • cardiac neuron CL0010022
    CSI 1.99
    rCSI 6.38%
    PRS 93.99
  • periportal region hepatocyte CL0019026
    CSI 1.93
    rCSI 7.5%
    PRS 91.55
  • Bergmann glial cell CL0000644
    CSI 1.93
    rCSI 2.63%
    PRS 89.48
  • Schwann cell CL0002573
    CSI 1.91
    rCSI 5.43%
    PRS 92.05
  • centrilobular region hepatocyte CL0019029
    CSI 1.82
    rCSI 4.75%
    PRS 91.03
  • tracheobronchial smooth muscle cell CL0019019
    CSI 1.72
    rCSI 3.03%
    PRS 96.4
  • epithelial cell of proximal tubule CL0002306
    CSI 1.6
    rCSI 3.9%
    PRS 90.09
  • epicardial adipocyte CL1000309
    CSI 1.5
    rCSI 4.89%
    PRS 92.72
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.44
    rCSI 3.51%
    PRS 84.45
  • regular atrial cardiac myocyte CL0002129
    CSI 1.44
    rCSI 4.63%
    PRS 91.8
  • neural progenitor cell CL0011020
    CSI 1.43
    rCSI 6.31%
    PRS 86.16
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.36
    rCSI 2.4%
    PRS 85.75
  • glial cell CL0000125
    CSI 1.11
    rCSI 4.22%
    PRS 89.93
  • forebrain radial glial cell CL0013000
    CSI 1.05
    rCSI 3.38%
    PRS 94.35
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.96
    rCSI 3.63%
    PRS 86.44
  • regular ventricular cardiac myocyte CL0002131
    CSI 0.89
    rCSI 5.53%
    PRS 90.1

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [ADHFE1](/details-gene/137872) (Alcohol Dehydrogenase Iron Containing 1) is a protein-coding gene that encodes a mitochondrial enzyme known as hydroxyacid-oxoacid transhydrogenase. This enzyme is primarily involved in metabolic pathways, including the interconversion of 2-oxoglutarate and 2-hydroxyglutarate and general lipid metabolism. Expression data indicate that **Overall**, [ADHFE1](/details-gene/137872) is a significant gene in various specialized, metabolically active cell types. It shows particularly high significance in [parietal epithelial cell](/details-cell/CL1000452)s of the kidney, [alveolar adventitial fibroblast](/details-cell/CL4028006)s in the lung, and [hepatocyte](/details-cell/CL0000182)s in the liver, suggesting a fundamental role in the core metabolic functions of these key organ systems. ## Cellular Roles and Expression Landscape The expression profile of [ADHFE1](/details-gene/137872) highlights its importance in cells with high metabolic and secretory demands across diverse tissues. **Overall**, its most significant expression is observed in epithelial and stromal cell populations. Top-ranking cells include [parietal epithelial cell](/details-cell/CL1000452)s (CSI: 9.39) and [kidney connecting tubule epithelial cell](/details-cell/CL1000768)s (CSI: 5.77), underscoring a prominent role in renal metabolic processes. In the lung, it is highly significant in both stromal cells like [alveolar adventitial fibroblast](/details-cell/CL4028006) (CSI: 9.23) and epithelial cells like [pulmonary alveolar type 2 cell](/details-cell/CL0002063) (CSI: 6.10), suggesting involvement in both structural maintenance and specialized functions such as surfactant production. Consistent with its name, [ADHFE1](/details-gene/137872) is highly expressed in [hepatocyte](/details-cell/CL0000182)s (CSI: 7.11), where it likely participates in central carbon and lipid metabolism. Its significance extends to other high-energy-demand cells, including [cardiac muscle cell](/details-cell/CL0000746)s (CSI: 5.07) and specialized epithelial barriers such as [retinal pigment epithelial cell](/details-cell/CL0002586) (CSI: 5.12) and [choroid plexus epithelial cell](/details-cell/CL0000706) (CSI: 3.06). This broad but specific expression pattern points to a housekeeping role in mitochondrial bioenergetics within cells that have substantial metabolic workloads. ## Pathways and Molecular Function Functionally, [ADHFE1](/details-gene/137872) is annotated as a mitochondrial matrix enzyme ([GO:0005759](https://www.ebi.ac.uk/QuickGO/term/GO:0005759)). Its core molecular activity is defined as hydroxyacid-oxoacid transhydrogenase activity ([GO:0047988](https://www.ebi.ac.uk/QuickGO/term/GO:0047988)), which is crucial for specific metabolic processes. The primary pathway associated with [ADHFE1](/details-gene/137872) is the [Interconversion of 2-oxoglutarate and 2-hydroxyglutarate](https://reactome.org/content/detail/R-HSA-880009) ([R-HSA-880009](https://reactome.org/content/detail/R-HSA-880009)). This process is vital for cellular metabolism, and its dysregulation is linked to metabolic disorders such as D-2-hydroxyglutaric aciduria ([Link](https://doi.org/10.1007/s10545-005-0114-x)). This function aligns with its role in broader metabolic processes ([R-HSA-1430728](https://reactome.org/content/detail/R-HSA-1430728)), including lipid metabolism ([GO:0006629](https://www.ebi.ac.uk/QuickGO/term/GO:0006629)) and aerobic respiration ([R-HSA-1428517](https://reactome.org/content/detail/R-HSA-1428517)). Its high expression in [hepatocyte](/details-cell/CL0000182)s, kidney epithelial cells, and cardiac muscle is therefore consistent with a role in managing metabolic intermediates within the Krebs cycle and related pathways in these high-energy tissues. ## Research Directions The specific and high expression of [ADHFE1](/details-gene/137872) in metabolically active tissues, coupled with its core enzymatic function, positions it as a key player in cellular bioenergetics and homeostasis. While its role in normal physiology is becoming clearer, its contribution to pathology, particularly in metabolic diseases and cancer, warrants further investigation. For instance, its expression has been noted in studies of hepatoblastoma, suggesting a potential role in tumor metabolism ([Link](https://doi.org/10.1038/sj.onc.1207782)). **Proposed Hypotheses:** 1. Given its high significance in [hepatocyte](/details-cell/CL0000182)s and its function in 2-oxoglutarate and lipid metabolism, dysregulation of [ADHFE1](/details-gene/137872) contributes to the pathogenesis of non-alcoholic fatty liver disease (NAFLD) by altering mitochondrial substrate utilization and promoting lipid accumulation. 2. In the lung, the high expression of [ADHFE1](/details-gene/137872) in [alveolar adventitial fibroblast](/details-cell/CL4028006)s is essential for maintaining mitochondrial fitness. Downregulation of this enzyme under stress conditions (e.g., hypoxia, inflammation) may lead to fibroblast-to-myofibroblast transition and contribute to the development of pulmonary fibrosis. **Experimental Approach:** To test the first hypothesis regarding NAFLD, a study could utilize CRISPR-Cas9 to knock out [ADHFE1](/details-gene/137872) in human iPSC-derived [hepatocyte](/details-cell/CL0000182)s or a hepatoma cell line (e.g., HepG2). These knockout and control cells would be cultured under lipotoxic conditions (e.g., treatment with palmitate and oleate). The functional consequences would be assessed by measuring mitochondrial respiration and glycolytic rates using a Seahorse XF Analyzer, quantifying intracellular lipid droplets via Oil Red O staining, and performing lipidomics to profile changes in fatty acid and triglyceride composition. **Therapeutic Potential:** As an intracellular mitochondrial enzyme, [ADHFE1](/details-gene/137872) is a challenging target for antibody-based therapies but may be amenable to modulation by small molecules. If its activity is found to be essential for the survival and proliferation of certain cancer cells, such as hepatoblastoma, developing a small molecule inhibitor could represent a viable therapeutic strategy. Conversely, if its reduced function contributes to metabolic diseases like NAFLD or certain acidurias, a small molecule activator or gene therapy approach could be explored to restore its enzymatic activity. Its tissue-specific expression pattern suggests that targeting it may have a focused effect with potentially limited systemic side effects.

Genular Protein ID: 164665343

Symbol: HOT_HUMAN

Name: Hydroxyacid-oxoacid transhydrogenase, mitochondrial

UniProtKB Accession Codes:

Q8IWW8 B4DTJ8 Q49A19 Q68CI7 Q6P2B6 Q96MF9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 8 ChEMBL 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EC 2 EMBL 8 Ensembl 3 ExpressionAtlas 1 GO 8 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 RNAct 1 Reactome 1 RefSeq 1 Rhea 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 12592711

Title: Cloning and characterization of a novel human alcohol dehydrogenase gene (ADHFe1).

PubMed ID: 12592711

DOI: 10.1080/1042517021000011636

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 15221005

Title: Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas.

PubMed ID: 15221005

DOI: 10.1038/sj.onc.1207782

PubMed ID: 16435184

Title: Kinetic characterization of human hydroxyacid-oxoacid transhydrogenase: relevance to D-2-hydroxyglutaric and gamma-hydroxybutyric acidurias.

PubMed ID: 16435184

DOI: 10.1007/s10545-005-0114-x

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 467
  • Mass: 50308
  • Checksum: C66E0EB15610A0E3
  • Sequence:
    • MAAAARARVA YLLRQLQRAA CQCPTHSHTY SQAPGLSPSG KTTDYAFEMA VSNIRYGAAV 
TKEVGMDLKN MGAKNVCLMT DKNLSKLPPV QVAMDSLVKN GIPFTVYDNV RVEPTDSSFM 
EAIEFAQKGA FDAYVAVGGG STMDTCKAAN LYASSPHSDF LDYVSAPIGK GKPVSVPLKP 
LIAVPTTSGT GSETTGVAIF DYEHLKVKIG ITSRAIKPTL GLIDPLHTLH MPARVVANSG 
FDVLCHALES YTTLPYHLRS PCPSNPITRP AYQGSNPISD IWAIHALRIV AKYLKRAVRN 
PDDLEARSHM HLASAFAGIG FGNAGVHLCH GMSYPISGLV KMYKAKDYNV DHPLVPHGLS 
VVLTSPAVFT FTAQMFPERH LEMAEILGAD TRTARIQDAG LVLADTLRKF LFDLDVDDGL 
AAVGYSKADI PALVKGTLPQ ERVTKLAPCP QSEEDLAALF EASMKLY