Details for: INHA

Gene ID: 3623

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: INHA

Ensembl ID: ENSG00000123999

Description: inhibin subunit alpha

Cell Significance Landscape

Associated with

Significant Cells

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

  • sst GABAergic cortical interneuron CL4023017
    CSI 4.27
    rCSI 5.51%
    PRS 97.96
  • extravillous trophoblast CL0008036
    CSI 3.15
    rCSI 3.9%
    PRS 98.89
  • syncytiotrophoblast cell CL0000525
    CSI 2.75
    rCSI 7.93%
    PRS 98.08
  • placental villous trophoblast CL2000060
    CSI 2.48
    rCSI 3.82%
    PRS 98.84
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 2.13
    rCSI 5.17%
    PRS 96.73
  • stromal cell of ovary CL0002132
    CSI 1.49
    rCSI 4.1%
    PRS 99.52
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.87
    rCSI 3.15%
    PRS 97.17

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

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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    • 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 [INHA](/details-gene/3623) encodes the inhibin alpha subunit, a key component of the inhibin A and B protein complexes. As a member of the transforming growth factor-beta (TGF-beta) superfamily, it functions primarily as a hormone and growth factor. [INHA](/details-gene/3623) plays a critical role in reproductive physiology, most notably through the negative regulation of pituitary follicle-stimulating hormone (FSH) secretion, thereby influencing gonadal function and gametogenesis ([Link](https://doi.org/10.1073/pnas.83.16.5849)). While its expression is well-established in reproductive tissues such as the [stromal cell of ovary](/details-cell/CL0002132) and placental trophoblasts, expression data also reveals a significant and specific role in distinct neuronal populations, including the [sst GABAergic cortical interneuron](/details-cell/CL4023017), suggesting uncharacterized functions in the central nervous system. Clinically, mutations and altered expression of [INHA](/details-gene/3623) are associated with premature ovarian failure ([Link](https://doi.org/10.1093/humrep/15.12.2644)) and certain gonadal tumors ([147380](https://omim.org/entry/147380)). ## Cellular Roles and Expression Landscape The expression profile of [INHA](/details-gene/3623) highlights its dual role in both reproductive endocrinology and neuronal function. **Overall**, the gene shows the highest significance in the [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 4.27), suggesting a highly specific and potentially crucial function within this inhibitory neuronal subtype. This is further supported by its significant expression in other neuronal cell types, such as the [L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040) (CSI: 2.13) and the [L5 extratelencephalic projecting glutamatergic cortical neuron](/details-cell/CL4023041) (CSI: 0.87). Concurrently, [INHA](/details-gene/3623) is a defining marker for several cell types essential for pregnancy and female reproductive health. It is highly significant in [extravillous trophoblast](/details-cell/CL0008036) (CSI: 3.15), [syncytiotrophoblast cell](/details-cell/CL0000525) (CSI: 2.75), and [placental villous trophoblast](/details-cell/CL2000060) (CSI: 2.48), underscoring its role in placental development and maternal-fetal communication. Its established function in ovarian physiology is confirmed by its notable significance in the [stromal cell of ovary](/details-cell/CL0002132) (CSI: 1.49). The collective expression pattern indicates that [INHA](/details-gene/3623) is not only a classical reproductive hormone but may also act as a local signaling molecule in specialized tissues like the cerebral cortex. ## Pathways and Molecular Function The functional annotations for [INHA](/details-gene/3623) are consistent with its identity as an extracellular signaling protein. Its molecular function is defined by its [cytokine activity](/details-go/GO:0005125), [growth factor activity](/details-go/GO:0008083), and [hormone activity](/details-go/GO:0005179). The alpha subunit forms heterodimers to create the [inhibin a complex](/details-go/GO:0043512) and [inhibin b complex](/details-go/GO:0043513), which are secreted into the [extracellular space](/details-go/GO:0005615). At the process level, [INHA](/details-gene/3623) is a central participant in the [Signaling by TGFB family members](/details-pathway/R-HSA-9006936) pathway. Its most well-characterized role is the [negative regulation of follicle-stimulating hormone secretion](/details-go/GO:0046882), which is fundamental to [ovarian follicle development](/details-go/GO:0001541) and [male gonad development](/details-go/GO:0008584). Beyond reproductive endocrinology, [INHA](/details-gene/3623) is implicated in the negative regulation of immune cell differentiation, including [b cell differentiation](/details-go/GO:0045578) and [macrophage differentiation](/details-go/GO:0045650), suggesting a potential immunomodulatory function. Its involvement in broader processes such as [cell differentiation](/details-go/GO:0030154), [regulation of cell population proliferation](/details-go/GO:0042127), and [signal transduction](/details-go/GO:0007165) highlights its pleiotropic effects as a signaling molecule. ## Research Directions The dual-expression pattern of [INHA](/details-gene/3623) in both reproductive and neuronal tissues, combined with its known role as a tumor suppressor, suggests several avenues for future research. **Proposed Hypotheses:** 1. Given its high and specific expression in [sst GABAergic cortical interneuron](/details-cell/CL4023017), [INHA](/details-gene/3623) may function as a local neuromodulator that regulates the activity or synaptic integration of these inhibitory neurons, thereby influencing cortical circuit balance and function independently of its systemic endocrine effects. 2. Based on reports that link germline mutations to ovarian tumors ([Link](https://doi.org/10.1002/humu.22489)) and loss of expression to prostate cancer progression ([Link](https://doi.org/10.1210/jcem.83.3.4640)), it is hypothesized that [INHA](/details-gene/3623) acts as a tumor suppressor in hormone-sensitive tissues. Its loss may disrupt local TGF-beta superfamily signaling, leading to uncontrolled cell proliferation and evasion of apoptosis. **Experimental Approach:** To test the first hypothesis regarding the neuromodulatory role of [INHA](/details-gene/3623), a targeted experimental approach could be employed. Conditional knockout of [INHA](/details-gene/3623) specifically in somatostatin-expressing neurons in mice would allow for precise investigation of its function. Electrophysiological recordings (e.g., whole-cell patch-clamp) from these neurons in cortical slices could be used to assess changes in intrinsic excitability, synaptic inputs, and network activity. Furthermore, behavioral assays relevant to cortical function, such as sensory processing or working memory tasks, could reveal the functional consequences of its deletion in this specific cell type. **Therapeutic Potential:** The existing evidence suggests [INHA](/details-gene/3623) functions as a tumor suppressor, particularly in ovarian and prostate cancers. Therefore, it is not a candidate for therapeutic inhibition. Instead, its clinical potential likely lies in diagnostics and as a potential target for activation. Low expression levels of [INHA](/details-gene/3623) in tumor biopsies could serve as a negative prognostic biomarker. Therapeutically, strategies aimed at restoring [INHA](/details-gene/3623) function, such as gene therapy or small molecules that enhance its expression or signaling pathway, could be explored for certain cancers. However, such activation strategies are complex and would require a deep understanding of its context-specific downstream signaling to avoid off-target effects.

Genular Protein ID: 3238398872

Symbol: INHA_HUMAN

Name: Inhibin alpha chain

UniProtKB Accession Codes:

P05111 A8K8H5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEMBL 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 ELM 1 EMBL 8 Ensembl 1 GO 32 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PIRSF 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 4 RefSeq 1 SIGNOR 1 SMART 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 3016724

Title: Inhibin A-subunit cDNAs from porcine ovary and human placenta.

PubMed ID: 3016724

DOI: 10.1073/pnas.83.16.5849

PubMed ID: 3758355

Title: Human inhibin genes. Genomic characterisation and sequencing.

PubMed ID: 3758355

DOI: 10.1016/0014-5793(86)81006-7

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: 3754442

Title: Structure of two human ovarian inhibins.

PubMed ID: 3754442

DOI: 10.1016/0006-291x(86)91021-1

PubMed ID: 8885240

Title: Characterization and determination of the biological activities of noncleavable high molecular weight forms of inhibin A and activin A.

PubMed ID: 8885240

DOI: 10.1210/mend.10.9.8885240

PubMed ID: 9506758

Title: Loss of the expression and localization of inhibin alpha-subunit in high grade prostate cancer.

PubMed ID: 9506758

DOI: 10.1210/jcem.83.3.4640

PubMed ID: 11098038

Title: Inhibin: a candidate gene for premature ovarian failure.

PubMed ID: 11098038

DOI: 10.1093/humrep/15.12.2644

PubMed ID: 24302632

Title: Germline mutations of inhibins in early-onset ovarian epithelial tumors.

PubMed ID: 24302632

DOI: 10.1002/humu.22489

Sequence Information:

  • Length: 366
  • Mass: 39670
  • Checksum: 0E03D2AB12BF8E57
  • Sequence:
    • MVLHLLLFLL LTPQGGHSCQ GLELARELVL AKVRALFLDA LGPPAVTREG GDPGVRRLPR 
RHALGGFTHR GSEPEEEEDV SQAILFPATD ASCEDKSAAR GLAQEAEEGL FRYMFRPSQH 
TRSRQVTSAQ LWFHTGLDRQ GTAASNSSEP LLGLLALSPG GPVAVPMSLG HAPPHWAVLH 
LATSALSLLT HPVLVLLLRC PLCTCSARPE ATPFLVAHTR TRPPSGGERA RRSTPLMSWP 
WSPSALRLLQ RPPEEPAAHA NCHRVALNIS FQELGWERWI VYPPSFIFHY CHGGCGLHIP 
PNLSLPVPGA PPTPAQPYSL LPGAQPCCAA LPGTMRPLHV RTTSDGGYSF KYETVPNLLT 
QHCACI