Details for: HSD17B14

Gene ID: 51171

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: HSD17B14

Ensembl ID: ENSG00000087076

Description: hydroxysteroid 17-beta dehydrogenase 14

Cell Significance Landscape

Associated with

Significant Cells

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

  • Hofbauer cell CL3000001
    CSI 10.25
    rCSI 19.35%
    PRS 95.91
  • intestinal epithelial cell CL0002563
    CSI 10.2
    rCSI 10.66%
    PRS 90.12
  • amacrine cell CL0000561
    CSI 6.47
    rCSI 18.74%
    PRS 84.92
  • neural progenitor cell CL0011020
    CSI 5.35
    rCSI 23.53%
    PRS 82.6
  • epithelial cell of proximal tubule CL0002306
    CSI 4.74
    rCSI 11.58%
    PRS 86.78
  • myofibroblast cell CL0000186
    CSI 4.52
    rCSI 6.27%
    PRS 89.32
  • Kupffer cell CL0000091
    CSI 4.32
    rCSI 9.87%
    PRS 93.19
  • elicited macrophage CL0000861
    CSI 4.11
    rCSI 3.77%
    PRS 95.85
  • pancreatic D cell CL0000173
    CSI 3.98
    rCSI 3.91%
    PRS 93.73
  • melanocyte CL0000148
    CSI 3.46
    rCSI 2.56%
    PRS 89.41
  • ON-bipolar cell CL0000749
    CSI 3.24
    rCSI 4.81%
    PRS 90.99
  • Mueller cell CL0000636
    CSI 3.15
    rCSI 7.2%
    PRS 86.73
  • pancreatic A cell CL0000171
    CSI 3.01
    rCSI 3.15%
    PRS 93.8
  • hematopoietic stem cell CL0000037
    CSI 2.91
    rCSI 1.94%
    PRS 93.46
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 2.4
    rCSI 9.06%
    PRS 81.39
  • bronchus fibroblast of lung CL2000093
    CSI 2.23
    rCSI 1.81%
    PRS 91.6
  • retinal pigment epithelial cell CL0002586
    CSI 2.12
    rCSI 4.2%
    PRS 89.37
  • choroid plexus epithelial cell CL0000706
    CSI 2.09
    rCSI 3.43%
    PRS 86.32
  • retina horizontal cell CL0000745
    CSI 2.05
    rCSI 3.12%
    PRS 89.4
  • alveolar macrophage CL0000583
    CSI 1.85
    rCSI 3.05%
    PRS 93.93
  • kidney epithelial cell CL0002518
    CSI 1.82
    rCSI 3.48%
    PRS 97.82
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.82
    rCSI 4.07%
    PRS 81.37
  • lung neuroendocrine cell CL1000223
    CSI 1.79
    rCSI 2.65%
    PRS 93.35
  • retinal ganglion cell CL0000740
    CSI 1.56
    rCSI 3.44%
    PRS 83.26
  • type B pancreatic cell CL0000169
    CSI 1.51
    rCSI 3.33%
    PRS 92.09
  • pancreatic epsilon cell CL0005019
    CSI 1.45
    rCSI 6.74%
    PRS 94.94
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.38
    rCSI 3.5%
    PRS 87.35
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.21
    rCSI 2.95%
    PRS 79.03
  • forebrain radial glial cell CL0013000
    CSI 1.19
    rCSI 3.83%
    PRS 91.93
  • stromal cell of ovary CL0002132
    CSI 1.17
    rCSI 3.23%
    PRS 94.72
  • pancreatic PP cell CL0002275
    CSI 1.09
    rCSI 4.33%
    PRS 94.78
  • podocyte CL0000653
    CSI 0.77
    rCSI 3.41%
    PRS 92.59
  • ON midget ganglion cell CL4033046
    CSI 0.42
    rCSI 8.59%
    PRS 84.75

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.

Comma-separated if multiple.
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 [HSD17B14](/details-gene/51171) encodes hydroxysteroid 17-beta dehydrogenase 14, a cytosolic enzyme that participates in the metabolism of steroid hormones. As a member of the short-chain dehydrogenase/reductase family, it exhibits estradiol and testosterone 17-beta-dehydrogenase activity, primarily contributing to steroid catabolism and biosynthesis pathways ([Link](https://doi.org/10.1042/bj20061319)). **Overall**, expression data indicate that [HSD17B14](/details-gene/51171) has its most significant roles in specialized cell types across diverse tissues, including placental macrophages ([Hofbauer cell](/details-cell/CL3000001)), [intestinal epithelial cell](/details-cell/CL0002563), and various neuronal and glial cells of the retina. This expression pattern suggests a key function in regulating local steroid hormone concentrations critical for tissue-specific physiological processes, such as immune modulation at the maternal-fetal interface and neuronal function. ## Cellular Roles and Expression Landscape The expression profile of [HSD17B14](/details-gene/51171) highlights its importance in cells with active steroid metabolism. Its highest significance is observed in [Hofbauer cell](/details-cell/CL3000001) (CSI: 10.25), a type of placental macrophage, and [intestinal epithelial cell](/details-cell/CL0002563) (CSI: 10.20), suggesting a primary role in regulating the steroid hormone environment in the placenta and the gut mucosa. Beyond these top-ranking cells, [HSD17B14](/details-gene/51171) shows a notable enrichment in the retina, with significant expression in [amacrine cell](/details-cell/CL0000561), [ON-bipolar cell](/details-cell/CL0000749), and [Mueller cell](/details-cell/CL0000636). This is consistent with literature highlighting the importance of dehydrogenases in retinal function ([Link](https://doi.org/10.1016/s0076-6879(00)16736-9)). Furthermore, its expression is significant in other specialized cell types, including macrophages such as [Kupffer cell](/details-cell/CL0000091) and [elicited macrophage](/details-cell/CL0000861), endocrine cells like [pancreatic D cell](/details-cell/CL0000173) and [pancreatic A cell](/details-cell/CL0000171), and renal [epithelial cell of proximal tubule](/details-cell/CL0002306). This widespread but cell-type-specific expression pattern points to a function in modulating local steroid signaling across multiple organ systems rather than a ubiquitous housekeeping role. ## Pathways and Molecular Function Functionally, [HSD17B14](/details-gene/51171) is firmly rooted in steroid metabolism. Gene Ontology annotations describe its molecular function as [Estradiol 17-beta-dehydrogenase [nad(p)+] activity](/details-go/GO0004303) and [Testosterone 17-beta-dehydrogenase (nadp+) activity](/details-go/GO0047045), contributing to the broader biological process of [Steroid catabolic process](/details-go/GO0006706). The enzyme is localized to the [Cytosol](/details-go/GO0005829). These functions are integrated into several key metabolic pathways, as detailed by Reactome. [HSD17B14](/details-gene/51171) is a component of the [Metabolism of steroid hormones](/details-pathway/R-HSA-196071) and specifically participates in [Estrogen biosynthesis](/details-pathway/R-HSA-193144). Its high expression in [Hofbauer cell](/details-cell/CL3000001) is consistent with this role, as the placenta is a primary site of estrogen synthesis during pregnancy. The protein's ability to engage in [identical protein binding](/details-go/GO0042802) suggests it may form homodimers or larger complexes to carry out its catalytic activity, a feature common to many dehydrogenases. ## Research Directions The specific expression pattern and enzymatic function of [HSD17B14](/details-gene/51171) present several avenues for future investigation. Its role appears to be providing fine-tuned, local control of active steroid hormone levels in specific cellular microenvironments. Based on the available data, several testable hypotheses can be proposed: 1. Given its top-ranking significance in [Hofbauer cell](/details-cell/CL3000001), [HSD17B14](/details-gene/51171) is critical for modulating the balance of estrogens and androgens at the maternal-fetal interface, thereby influencing immune tolerance and preventing fetal rejection. 2. The high expression of [HSD17B14](/details-gene/51171) in diverse retinal cell types suggests it metabolizes neurosteroids or retinoids essential for retinal health and visual processing, and its dysregulation could contribute to retinal degenerative diseases. 3. In the gut, [HSD17B14](/details-gene/51171) expression in [intestinal epithelial cell](/details-cell/CL0002563) may regulate mucosal immune responses and barrier integrity by locally catabolizing pro-inflammatory steroids. To test the first hypothesis regarding its placental role, a compelling experimental approach would be to use CRISPR-Cas9 to knock out [HSD17B14](/details-gene/51171) in a human trophoblast-macrophage co-culture system. Subsequent analysis using liquid chromatography-mass spectrometry (LC-MS) could quantify changes in local steroid profiles (e.g., estradiol-to-testosterone ratio), while multiplex immunoassays (e.g., Luminex) could assess the downstream effects on cytokine and chemokine secretion relevant to immune suppression (e.g., IL-10, TGF-beta). As a therapeutic target, [HSD17B14](/details-gene/51171) holds potential for conditions characterized by localized steroid dysregulation. Because it is a cytosolic enzyme, it is amenable to targeting by small molecule inhibitors. For hormone-sensitive conditions or localized inflammation, inhibiting [HSD17B14](/details-gene/51171) could offer a tissue-specific alternative to systemic hormonal therapies, potentially reducing side effects. For example, in inflammatory bowel disease, a locally acting inhibitor could modulate gut mucosal steroid levels without inducing systemic effects. Therefore, selective inhibition represents the most probable therapeutic strategy.

Genular Protein ID: 3357174800

Symbol: DHB14_HUMAN

Name: 17-beta-hydroxysteroid dehydrogenase DHRS10

UniProtKB Accession Codes:

Q9BPX1 Q9UKU3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 12 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 4 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 5 Gene3D 1 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 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 31 PDBsum 31 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 Rhea 4 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissLipids 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 10800688

Title: Short-chain dehydrogenases/reductases in retina.

PubMed ID: 10800688

DOI: 10.1016/s0076-6879(00)16736-9

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

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: 17067289

Title: Structural and biochemical characterization of human orphan DHRS10 reveals a novel cytosolic enzyme with steroid dehydrogenase activity.

PubMed ID: 17067289

DOI: 10.1042/bj20061319

Sequence Information:

  • Length: 270
  • Mass: 28317
  • Checksum: DAB68FB8CA422ABC
  • Sequence:
    • MATGTRYAGK VVVVTGGGRG IGAGIVRAFV NSGARVVICD KDESGGRALE QELPGAVFIL 
CDVTQEDDVK TLVSETIRRF GRLDCVVNNA GHHPPPQRPE ETSAQGFRQL LELNLLGTYT 
LTKLALPYLR KSQGNVINIS SLVGAIGQAQ AVPYVATKGA VTAMTKALAL DESPYGVRVN 
CISPGNIWTP LWEELAALMP DPRATIREGM LAQPLGRMGQ PAEVGAAAVF LASEANFCTG 
IELLVTGGAE LGYGCKASRS TPVDAPDIPS