Details for: REC114

Gene ID: 283677

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: REC114

Ensembl ID: ENSG00000183324

Description: REC114 meiotic recombination protein

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • cardiac muscle cell CL0000746
    CSI 3.59
    rCSI 5.15%
    PRS 99.63
  • regular atrial cardiac myocyte CL0002129
    CSI 2.55
    rCSI 8.21%
    PRS 99.89
  • basal cell of epidermis CL0002187
    CSI 2.09
    rCSI 3.71%
    PRS 96.84

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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  • Node Size: Proportional to Target Cell CSI magnitude
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  • 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 [REC114](/details-gene/283677) is a protein-coding gene located on chromosome 15q24.1 that plays an essential role in the initiation of meiotic recombination. Functional annotations link it directly to processes such as [Dna recombination](/details-go/GO:0006310) and [Meiotic dna double-strand break formation](/details-go/GO:0042138). Consistent with this, research has demonstrated that homozygous loss-of-function mutations in [REC114](/details-gene/283677) lead to severe reproductive consequences, including female infertility due to early embryonic arrest and male infertility caused by meiotic arrest and nonobstructive azoospermia ([Link](https://doi.org/10.1136/jmedgenet-2019-106379), [Link](https://doi.org/10.1111/cge.14473)). While its primary function is in gametogenesis, expression data intriguingly suggests its significant presence in somatic cell types, including [cardiac muscle cell](/details-cell/CL0000746), indicating potential uncharacterized functions. ## Cellular Roles and Expression Landscape The established function of [REC114](/details-gene/283677) is fundamentally tied to germline cells during meiosis. Its involvement in [Spermatogenesis](/details-go/GO:0007283) and [Oogenesis](/details-go/GO:0048477) is critical for the proper formation of gametes. It localizes to the [Chromosome](/details-go/GO:0005694) where it facilitates the creation of DNA double-strand breaks, a necessary first step for homologous recombination. However, a broader analysis of its expression profile reveals a more complex picture. **Overall**, the highest significance scores for [REC114](/details-gene/283677) expression are observed in somatic cell types, which is unexpected given its canonical meiotic role. The top three cell types with the highest cell significance index (CSI) are: - [cardiac muscle cell](/details-cell/CL0000746) (CSI: 3.59) - [regular atrial cardiac myocyte](/details-cell/CL0002129) (CSI: 2.55) - [basal cell of epidermis](/details-cell/CL0002187) (CSI: 2.09) This high level of expression in terminally differentiated, non-dividing cells like cardiac myocytes and in progenitor cells like basal cells suggests that [REC114](/details-gene/283677) may possess pleiotropic functions beyond meiosis. Its role in these somatic tissues is currently uncharacterized and warrants further investigation. ## Pathways and Molecular Function The molecular functions of [REC114](/details-gene/283677) are centered on its role as a key initiator of meiotic recombination. It is a critical component of the machinery that creates programmed DNA double-strand breaks (DSBs), a process essential for generating genetic diversity and ensuring proper chromosome segregation during meiosis. Key annotated functions include: * **Biological Process:** As a central actor in [Meiotic dna double-strand break formation](/details-go/GO:0042138), [REC114](/details-gene/283677) is indispensable for both [Spermatogenesis](/details-go/GO:0007283) and [Oogenesis](/details-go/GO:0048477). This is strongly supported by clinical findings where its absence leads to infertility ([Link](https://doi.org/10.1136/jmedgenet-2019-106379), [Link](https://doi.org/10.1111/cge.14473)). * **Molecular Function:** Its ability to participate in these processes likely relies on its annotated function in [Protein binding](/details-go/GO:0005515), suggesting it operates as part of a larger protein complex on meiotic chromosomes. * **Cellular Component:** Consistent with its function in DNA metabolism, it is localized to the [Chromosome](/details-go/GO:0005694). The expression of [REC114](/details-gene/283677) in somatic cells like cardiac myocytes is enigmatic, as these cells are post-mitotic and do not undergo recombination. This suggests either a yet-to-be-discovered function, possibly related to DNA damage repair or chromatin organization in long-lived cells, or that the observed expression is a non-functional transcript. ## Research Directions The discrepancy between the well-established meiotic function of [REC114](/details-gene/283677) and its observed high expression in somatic tissues like cardiac muscle presents a compelling area for future research. ### Proposed Hypotheses: 1. **Somatic DNA Repair Hypothesis:** [REC114](/details-gene/283677) possesses a secondary, uncharacterized function in somatic cells, particularly in long-lived, terminally differentiated cells like cardiac myocytes, where it may contribute to DNA integrity and repair pathways distinct from canonical meiotic recombination. 2. **Transcriptional Noise Hypothesis:** The detection of [REC114](/details-gene/283677) transcripts in somatic cells is a result of transcriptional leakage or promiscuity and does not result in a functionally relevant protein product in these cellular contexts. ### Experimental Approach: To test the **Somatic DNA Repair Hypothesis**, one could utilize human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). [REC114](/details-gene/283677) expression could be knocked down using CRISPR interference (CRISPRi) or shRNA. These knockdown iPSC-CMs, along with isogenic controls, would then be subjected to a DNA-damaging agent (e.g., doxorubicin, a known cardiotoxic agent). The cellular response to DNA damage could be quantified by assessing levels of γ-H2AX foci formation, cell viability, and the efficiency of DNA repair using a comet assay. A significant increase in DNA damage or reduced viability in the knockdown cells would provide strong evidence for a functional role of [REC114](/details-gene/283677) in somatic DNA maintenance. ### Therapeutic Potential: Given that loss-of-function mutations in [REC114](/details-gene/283677) cause infertility, it is not a candidate for therapeutic inhibition. The potential for therapeutic activation or gene replacement therapy could be considered for specific forms of monogenic infertility caused by [REC114](/details-gene/283677) deficiency. However, the technical and ethical challenges of germline gene editing are substantial. If a role in somatic DNA repair is confirmed, particularly in the context of cardiotoxicity or aging, pathways involving [REC114](/details-gene/283677) might become targets for modulation, but direct targeting of the gene itself appears unlikely at present.

Genular Protein ID: 4104419593

Symbol: RE114_HUMAN

Name: Meiotic recombination protein REC114

UniProtKB Accession Codes:

Q7Z4M0

Database IDs:

AGR 1 AlphaFoldDB 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 1 ExpressionAtlas 1 GO 5 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 3 MalaCards 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 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: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

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: 31704776

Title: Homozygous mutations in REC114 cause female infertility characterised by multiple pronuclei formation and early embryonic arrest.

PubMed ID: 31704776

DOI: 10.1136/jmedgenet-2019-106379

PubMed ID: 38148155

Title: A bi-allelic REC114 loss-of-function variant causes meiotic arrest and nonobstructive azoospermia.

PubMed ID: 38148155

DOI: 10.1111/cge.14473

Sequence Information:

  • Length: 266
  • Mass: 29155
  • Checksum: CCF8C194201A5AA1
  • Sequence:
    • MAEAGKVPLS LGLTGGEAAE WPLQRYARCI PSNTRDPPGP CLEAGTAPCP TWKVFDSNEE 
SGYLVLTIVI SGHFFIFQGQ TLLEGFSLIG SKDWLKIVRR VDCLLFGTTI KDKSRLFRVQ 
FSGESKEQAL EHCCSCVQKL AQYITVQVPD GNIQELQLIP GPPRATESQG KDSAKSVPRQ 
PGSHQHSEQQ QVCVTAGTGA PDGRTSLTQL AQTLLASEEL PHVYEQSAWG AEELGPFLRL 
CLMDQNFPAF VEEVEKELKK LAGLRN

Genular Protein ID: 232226592

Symbol: H0YKR2_HUMAN

Name: N/A

UniProtKB Accession Codes:

H0YKR2

Database IDs:

Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 2 GeneTree 1 HGNC 1 InterPro 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 Proteomes 2 ProteomicsDB 2 RefSeq 1 SAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

Sequence Information:

  • Length: 238
  • Mass: 25977
  • Checksum: 76E5B4905BFC15E9
  • Sequence:
    • MAEAGKVPLS LGLTGGEAAE WPLQRYARCI PSNTRDPPGP CLEAGTAPCP TWKVFDSNEE 
SGYLVLTIVI SGHFFIFQGQ TLLDKSRLFR VQFSGESKEQ ALEHCCSCVQ KLAQYITVQV 
PDGNIQELQL IPGPPRATES QGKDSAKSVP RQPGSHQHSE QQQVCVTAGT GAPDGRTSLT 
QLAQTLLASE ELPHVYEQSA WGAEELGPFL RLCLMDQNFP AFVEEVEKEL KKLAGLRN