Details for: C14orf39

Gene ID: 317761

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: C14orf39

Ensembl ID: ENSG00000179008

Description: chromosome 14 open reading frame 39

Cell Significance Landscape

Associated with

Significant Cells

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

  • Mueller cell CL0000636
    CSI 4.3
    rCSI 9.82%
    PRS 96.74
  • retinal ganglion cell CL0000740
    CSI 2.89
    rCSI 6.38%
    PRS 95.53
  • amacrine cell CL0000561
    CSI 2.03
    rCSI 5.9%
    PRS 95.81
  • retinal cone cell CL0000573
    CSI 2.03
    rCSI 3.27%
    PRS 95.94
  • H2 horizontal cell CL0004218
    CSI 1.83
    rCSI 9.11%
    PRS 96.03
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.72
    rCSI 6.52%
    PRS 95.13
  • S cone cell CL0003050
    CSI 1.68
    rCSI 7.39%
    PRS 96.78
  • GABAergic amacrine cell CL4030027
    CSI 1.24
    rCSI 4.25%
    PRS 93.33
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.16
    rCSI 4.17%
    PRS 94.88
  • ON midget ganglion cell CL4033046
    CSI 0.87
    rCSI 17.79%
    PRS 95.08
  • OFF midget ganglion cell CL4033047
    CSI 0.75
    rCSI 15.29%
    PRS 95.05
  • ON parasol ganglion cell CL4033052
    CSI 0.5
    rCSI 7.09%
    PRS 95.02

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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Legend:
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  • 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 [C14orf39](/details-gene/317761), also known as *SIX6OS1*, is a protein-coding gene located on chromosome 14q23.1. Functionally, it is critically involved in meiosis, with established roles in [synaptonemal complex assembly](/details-go/GO:0007130) and [homologous chromosome pairing](/details-go/GO:0007129). Consistent with this, homozygous loss-of-function mutations in [C14orf39](/details-gene/317761) have been shown to cause non-obstructive azoospermia in males and premature ovarian insufficiency in females, highlighting its essential role in human fertility [Link](https://doi.org/10.1016/j.ajhg.2021.01.010). Intriguingly, expression data reveals that its most significant cellular signature is not in germline cells but in various specialized cell types of the neural retina, including [Mueller cells](/details-cell/CL0000636) and [retinal ganglion cells](/details-cell/CL0000740). This suggests a potential moonlighting function or a role in retinal development, which remains to be fully elucidated. ## Cellular Roles and Expression Landscape The expression profile of [C14orf39](/details-gene/317761) demonstrates a highly specific and significant enrichment in the central nervous system, particularly within the retina. **Overall**, the gene shows its highest cell significance index (CSI) in [Mueller cells](/details-cell/CL0000636) (CSI: 4.30), a type of retinal glial cell essential for retinal homeostasis and neuronal support. Following this, [C14orf39](/details-gene/317761) is a prominent marker across a spectrum of retinal neurons, including: * [retinal ganglion cell](/details-cell/CL0000740) (CSI: 2.89) * [amacrine cell](/details-cell/CL0000561) (CSI: 2.03) * [retinal cone cell](/details-cell/CL0000573) (CSI: 2.03) * [H2 horizontal cell](/details-cell/CL0004218) (CSI: 1.83) Beyond the retina, significant expression is also noted in specific subtypes of cortical neurons, such as [near-projecting glutamatergic cortical neurons](/details-cell/CL4023012) and [L5 extratelencephalic projecting glutamatergic cortical neurons](/details-cell/CL4023041). This highly restricted expression pattern points towards a specialized function within terminally differentiated neural cell types, which contrasts with its established role in meiotic processes within the germline. ## Pathways and Molecular Function Functional annotation strongly supports the role of [C14orf39](/details-gene/317761) in reproduction and gamete formation. The gene is significantly associated with biological processes crucial for meiosis, including [homologous chromosome pairing at meiosis](/details-go/GO:0007129), [synaptonemal complex assembly](/details-go/GO:0007130), and [meiotic dna double-strand break processing involved in reciprocal meiotic recombination](/details-go/GO:0010705). These functions are fundamental to both [spermatogenesis](/details-go/GO:0007283) and [oogenesis](/details-go/GO:0048477). At the molecular level, the protein product, SIX6OS1, is known to be a component of the [chromosome](/details-go/GO:0005694) and localizes specifically to the [central element](/details-go/GO:0000801) of the synaptonemal complex, a proteinaceous structure that mediates chromosome synapsis during prophase I. This localization is consistent with its function in mediating the pairing of homologous chromosomes. While the molecular function is broadly annotated as [protein binding](/details-go/GO:0005515), its specific binding partners that facilitate these meiotic processes are an area of active investigation. The stark contrast between this well-defined meiotic function and its high expression in the retina suggests uncharacterized roles in neural biology. ## Research Directions The most compelling question arising from the available data is the dichotomy between the established meiotic function of [C14orf39](/details-gene/317761) and its highly specific, abundant expression in the mature retina. This disconnect presents several avenues for future research. **Proposed Hypotheses:** 1. [C14orf39](/details-gene/317761) possesses a moonlighting function in the retina, where it is repurposed for a role unrelated to meiosis, such as maintaining synaptic architecture, regulating gene expression for neuronal maintenance, or contributing to the structural integrity of retinal glial cells. 2. The high expression of [C14orf39](/details-gene/317761) in the retina is primarily critical during development, potentially sharing a pathway with early eye development as previously suggested [Link](https://doi.org/10.1093/hmg/ddi084), and its continued high expression in adult retinal cells is a stable remnant of this developmental role. **Experimental Approach:** To test the hypothesis of a moonlighting function in the adult retina (Hypothesis 1), a valuable experiment would be to generate a conditional knockout mouse model. Using a Cre-Lox system, the *Six6os1* gene (the mouse ortholog) could be specifically deleted in mature retinal cells (e.g., using a Pcp2-Cre driver for specific retinal neurons or a Gfap-Cre driver for glia). The resulting phenotype could be assessed using electroretinography (ERG) to measure retinal function and optical coherence tomography (OCT) for structural analysis. Furthermore, single-cell RNA sequencing on the knockout retinas could reveal cell-type-specific transcriptional dysregulation, providing mechanistic insight into the gene's function. **Therapeutic Potential:** Given that mutations in [C14orf39](/details-gene/317761) cause infertility through a loss-of-function mechanism [Link](https://doi.org/10.1016/j.ajhg.2021.01.010), the therapeutic strategy would be activation or gene replacement rather than inhibition. For treating infertility, this could theoretically involve gene therapy aimed at patient-derived germline stem cells, though such approaches face significant technical and ethical challenges. The gene is not an obvious target for common diseases, and its high specificity for the retina would make any systemic therapy targeting this gene require careful monitoring for off-target ocular effects.

Genular Protein ID: 1643645933

Symbol: S6OS1_HUMAN

Name: Protein SIX6OS1

UniProtKB Accession Codes:

Q8N1H7 Q08AQ4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 8 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 5 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 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 1 RNAct 1 RefSeq 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 12508121

Title: The DNA sequence and analysis of human chromosome 14.

PubMed ID: 12508121

DOI: 10.1038/nature01348

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: 15703187

Title: Natural antisense transcripts associated with genes involved in eye development.

PubMed ID: 15703187

DOI: 10.1093/hmg/ddi084

PubMed ID: 33508233

Title: Homozygous mutations in C14orf39/SIX6OS1 cause non-obstructive azoospermia and premature ovarian insufficiency in humans.

PubMed ID: 33508233

DOI: 10.1016/j.ajhg.2021.01.010

Sequence Information:

  • Length: 587
  • Mass: 68166
  • Checksum: A9EBB4EA5D689FC8
  • Sequence:
    • MNDSLFVSLD RLLLEFVFQY EQDISTKEEM IQRINKCCED IKENKVTICR IHETINATDE 
EIDHYCKHSE EIKDNCRNWK PTCDVFRKHE DYMQDQFTVY QGTVEKDKEM YHDYICQYKE 
VLKQYQLKYS ETPFSREYYE KKREHEEIQS RVLACTEQLK MNETIFMKFR VPAPFPSLTK 
WTLNIVNLRC ETQDILKHAS NLTKSSSELK KEVDEMEIEI NYLNQQISRH NETKALSETL 
EEKNKNTENR KELKERIFGK DEHVLTLNKT QSSQLFLPYE SQKLVRPIKM HSSEPRVADI 
KEESSAKQSK LANIDFRQKE NDTQIFNDSA VDNHSKCSHI TTITSSQKFM QVRLLTPQKQ 
SNSNQWSEKG DKDAEYGDKG TVRQVRESKC TSQAIYTEHF GKSVENDSDE VEERAENFPR 
TSEIPIFLGT PKAVKAPESL EKIKFPKTPP FEINRNRNAV PEVQTEKESP GLSFLMSYTS 
RSPGLNLFDS SVFDTEISSD QFNEHYSARN LNPLSSEQEI GNLLEKPEGE DGFTFSFPSD 
TSTHTFGAGK DDFSFPFSFG QGQNSIPSSS LKGFSSSSQN TTQFTFF