Details for: ARMC3

Gene ID: 219681

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: ARMC3

Ensembl ID: ENSG00000165309

Description: armadillo repeat containing 3

Cell Significance Landscape

Associated with

Significant Cells

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

  • ciliated epithelial cell CL0000067
    CSI 39.65
    rCSI 34.87%
    PRS 99.55
  • ependymal cell CL0000065
    CSI 35.04
    rCSI 71.1%
    PRS 98.85
  • lung ciliated cell CL1000271
    CSI 25.63
    rCSI 29.63%
    PRS 99.81
  • multi-ciliated epithelial cell CL0005012
    CSI 22.15
    rCSI 22.11%
    PRS 99.81
  • ciliated cell CL0000064
    CSI 14.32
    rCSI 23.2%
    PRS 99.56
  • choroid plexus epithelial cell CL0000706
    CSI 13.65
    rCSI 22.36%
    PRS 99.64
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 12.63
    rCSI 15.3%
    PRS 96.58
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 11.55
    rCSI 26.33%
    PRS 99.67
  • glioblast CL0000030
    CSI 10.95
    rCSI 17.47%
    PRS 99.78
  • squamous epithelial cell CL0000076
    CSI 10.19
    rCSI 24.19%
    PRS 99.44
  • deuterosomal cell CL4033044
    CSI 6.89
    rCSI 23.28%
    PRS 99.74
  • innate lymphoid cell CL0001065
    CSI 6.17
    rCSI 12.75%
    PRS 98.93
  • retinal cone cell CL0000573
    CSI 4.74
    rCSI 7.63%
    PRS 99.29
  • fallopian tube secretory epithelial cell CL4030006
    CSI 4.36
    rCSI 4.2%
    PRS 99.83
  • parietal epithelial cell CL1000452
    CSI 4.23
    rCSI 11.31%
    PRS 99.86
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 4.02
    rCSI 14.46%
    PRS 99.52
  • cytotoxic T cell CL0000910
    CSI 3.44
    rCSI 19.72%
    PRS 99.08
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.42
    rCSI 34.28%
    PRS 99.16
  • direct pathway medium spiny neuron CL4023026
    CSI 1.35
    rCSI 32.21%
    PRS 99.21

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 **[ARMC3](/details-gene/219681)** (Armadillo Repeat Containing 3) is a protein-coding gene whose expression is highly specific to cells featuring motile cilia or flagella. Its strong and selective expression in cell types such as [ciliated epithelial cells](/details-cell/CL0000067) and [ependymal cells](/details-cell/CL0000065) suggests a fundamental role in ciliary structure or function. Functional annotations link **[ARMC3](/details-gene/219681)** to processes including [flagellated sperm motility](/details-gene/GO:0030317) and [spermatid development](/details-gene/GO:0007286), underscoring its importance in male fertility. Recent evidence also implicates it in specialized cellular remodeling processes like [ribophagy](/details-gene/GO:0034517) during spermiogenesis [Link](https://doi.org/10.1016/j.devcel.2021.07.015). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of **[ARMC3](/details-gene/219681)** strongly indicates its function as a key component of motile cilia and flagella. The gene shows its highest significance in a range of ciliated cell types, which are crucial for fluid and particle transport in various organs. * **Dominant Expression in Ciliated Tissues:** The gene's highest significance scores are observed in [ciliated epithelial cell](/details-cell/CL0000067) (CSI: 39.65), [ependymal cell](/details-cell/CL0000065) (CSI: 35.04) lining the brain's ventricles, [lung ciliated cell](/details-cell/CL1000271) (CSI: 25.63), and [multi-ciliated epithelial cell](/details-cell/CL0005012) (CSI: 22.15). This pattern establishes **[ARMC3](/details-gene/219681)** as a defining marker for cells that depend on ciliary motion. * **Specialized Roles:** Expression is also noted in cells with precursor or specialized ciliary roles, such as [deuterosomal cells](/details-cell/CL4033044) (CSI: 6.89), which are involved in centriole amplification during ciliogenesis. Its presence in [choroid plexus epithelial cells](/details-cell/CL0000706) (CSI: 13.65) is also consistent with this theme, as these cells are both ciliated and involved in cerebrospinal fluid production. * **Other Contexts:** While primarily a marker of ciliated cells, lower but significant expression is detected in other cell types, including [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 12.63) and [glioblast](/details-cell/CL0000030) (CSI: 10.95), though the functional relevance in these contexts is less clear. The restricted expression pattern underscores a specialized biological function rather than a general housekeeping role. ## Pathways and Molecular Function Functional annotations for **[ARMC3](/details-gene/219681)** align closely with its cellular expression profile, pointing to a critical role in the biology of male gametes and ciliary function. * **Spermatogenesis and Motility:** **[ARMC3](/details-gene/219681)** is annotated with the Gene Ontology (GO) biological processes of [spermatid development](/details-gene/GO:0007286) and [flagellated sperm motility](/details-gene/GO:0030317). This is consistent with the structural and functional similarities between cilia and the sperm flagellum. The process of spermiogenesis involves extensive cellular remodeling to produce a motile spermatozoon. * **Ribophagy during Sperm Development:** The gene is also associated with [ribophagy](/details-gene/GO:0034517), the selective autophagic degradation of ribosomes. This process is critical during late spermiogenesis, where the elimination of excess cytoplasm and organelles is required. This degradation provides a source of energy that supports the final stages of sperm maturation and flagellar assembly [Link](https://doi.org/10.1016/j.devcel.2021.07.015). * **Cellular Localization:** In terms of cellular components, **[ARMC3](/details-gene/219681)** has been identified in the [extracellular exosome](/details-gene/GO:0070062), suggesting it may be secreted or shed from cells, although its primary function is likely intracellular. ## Research Directions The specific expression pattern and functional annotations of **[ARMC3](/details-gene/219681)** provide a basis for several testable hypotheses regarding its role in health and disease. **Proposed Hypotheses:** 1. **[ARMC3](/details-gene/219681)** is a structural or regulatory component of the ciliary axoneme, and its loss-of-function leads to primary ciliary dyskinesia (PCD), a human genetic disorder characterized by impaired ciliary motility. 2. During spermiogenesis, **[ARMC3](/details-gene/219681)** acts as an adaptor protein that targets ribosomes for autophagic degradation, and its absence results in male infertility due to failed cytoplasmic remodeling and defective flagellar function. 3. The aberrant re-expression of **[ARMC3](/details-gene/219681)**, a known cancer-testis antigen [Link](https://doi.org/10.1158/1078-0432.ccr-05-1206), in somatic cancers like lung or pancreatic cancer, contributes to tumorigenesis by promoting cell motility or interfering with normal cellular degradation pathways. **Experimental Approach:** To test the hypothesis that **[ARMC3](/details-gene/219681)** mediates ribophagy during spermatogenesis (Hypothesis 2), a germ-cell-specific conditional knockout mouse model could be generated. Testes from knockout and wild-type mice would be compared using transmission electron microscopy to assess for defects in spermatid cytoplasmic removal and the persistence of ribosomes in mature sperm. Co-immunoprecipitation of tagged **[ARMC3](/details-gene/219681)** from an in-vitro spermatogenesis system followed by mass spectrometry would be used to identify its protein interactors within the autophagy machinery. A direct interaction with ribosomal proteins or core autophagy components (e.g., LC3) would provide strong mechanistic evidence. **Therapeutic Potential:** Given its highly restricted expression in healthy somatic tissues and its documented re-expression in several cancers, **[ARMC3](/details-gene/219681)** represents a promising target for cancer therapy. As a cancer-testis antigen, it is likely to be immunogenic. Therefore, it is an excellent candidate for immunotherapeutic strategies, such as the development of therapeutic vaccines or engineered T-cell therapies (e.g., CAR-T or TCR-T) designed to recognize and eliminate tumor cells expressing **[ARMC3](/details-gene/219681)**. The therapeutic strategy would focus on targeted inhibition or elimination of the cancer cells that aberrantly express this protein.

Genular Protein ID: 404213988

Symbol: ARMC3_HUMAN

Name: Armadillo repeat-containing protein 3

UniProtKB Accession Codes:

Q5W041 A0PG76 A6NH64 B4DZL3 B7ZBN6 B7ZBN7 Q8IXS5 Q8N7B0 Q96M49

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 11 Ensembl 3 ExpressionAtlas 1 GO 4 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 RNAct 1 RefSeq 4 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 16915934

Title: Cloning and expression of ARMC3_v2, a novel splicing variant of the human ARMC3 gene.

PubMed ID: 16915934

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

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: 16397042

Title: A novel cancer testis antigen that is frequently expressed in pancreatic, lung, and endometrial cancers.

PubMed ID: 16397042

DOI: 10.1158/1078-0432.ccr-05-1206

PubMed ID: 34428398

Title: Autophagic elimination of ribosomes during spermiogenesis provides energy for flagellar motility.

PubMed ID: 34428398

DOI: 10.1016/j.devcel.2021.07.015

Sequence Information:

  • Length: 872
  • Mass: 96405
  • Checksum: 02ED1C432D961857
  • Sequence:
    • MGKKIKKEVE PPPKDVFDPL MIESKKAATV VLMLNSPEEE ILAKACEAIY KFALKGEENK 
TTLLELGAVE PLTKLLTHED KIVRRNATMI FGILASNNDV KKLLRELDVM NSVIAQLAPE 
EEVVIHEFAS LCLANMSAEY TSKVQIFEHG GLEPLIRLLS SPDPDVKKNS MECIYNLVQD 
FQCRAKLQEL NAIPPILDLL KSEYPVIQLL ALKTLGVIAN DKESRTMLRD NQGLDHLIKI 
LETKELNDLH IEALAVIANC LEDMDTMVQI QQTGGLKKLL SFAENSTIPD IQKNAAKAIT 
KAAYDPENRK LFHEQEVEKC LVALLGSEND GTKIAASQAI SAMCENSGSK DFFNNQGIPQ 
LIQLLKSDNE EVREAAALAL ANLTTCNPAN ANAAAEADGI DPLINLLSSK RDGAIANAAT 
VLTNMAMQEP LRLNIQNHDI MHAIISPLRS ANTVVQSKAA LAVTATACDV EARTELRNSG 
GLEPLVELLR SKNDEVRKHA SWAVMVCAGD ELTANELCRL GALDILEEVN VSGTRKNKFS 
EAAYNKLLNN NLSLKYSQTG YLSSSNIIND GFYDYGRINP GTKLLPLKEL CLQEPSDLRA 
VLLINSKSYV SPPSSMEDKS DVGYGRSISS SSSLRRSSKE KNKKNSYHFS AGFGSPIEDK 
SEPASGRNTV LSKSATKEKG WRKSKGKKEE EKVKEEEEVM VVPKFVGEGS SDKEWCPPSD 
PDFSMYVYEV TKSILPITNI KEQIEDLAKY VAEKMGGKIP KEKLPDFSWE LHISELKFQL 
KSNVIPIGHV KKGIFYHRAL LFKALADRIG IGCSLVRGEY GRAWNEVMLQ NDSRKGVIGG 
LPAPEMYVID LMFHPGGLMK LRSREADLYR FI

Genular Protein ID: 1006752374

Symbol: B4DXS3_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DXS3

Database IDs:

ARBA 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 2 Gene3D 1 GeneTree 1 HGNC 1 InterPro 4 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 1 PROSITE-ProRule 1 PeptideAtlas 1 Pfam 3 Proteomes 2 ProteomicsDB 2 RefSeq 1 SAM 1 SMART 1 SUPFAM 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: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

Sequence Information:

  • Length: 609
  • Mass: 66985
  • Checksum: 1E8948CD7803DDE1
  • Sequence:
    • MDTMVQIQQT GGLKKLLSFA ENSTIPDIQK NAAKAITKAA YDPENRKLFH EQEVEKCLVA 
LLGSENDGTK IAASQAISAM CENSGSKDFF NNQGIPQLIQ LLKSDNEEVR EAAALALANL 
TTCNPANANA AAEADGIDPL INLLSSKRDG AIANAATVLT NMAMQEPLRL NIQNHDIMHA 
IISPLRSANT VVQSKAALAV TATACDVEAR TELRNSGGLE PLVELLRSKN DEVRKHASWA 
VMVCAGDELT ANELCRLGAL DILEEVNVSG TRKNKFSEAA YNKLLNNNLS LKYSQTGYLS 
SSNIINDGFY DYGRINPGTK LLPLKELCLQ EPSDLRAVLL INSKSYVSPP SSMEDKSDVG 
YGRSISSSSS LRRSSKEKNK KNSYHFSAGF GSPIEDKSEP ASGRNTVLSK SATKEKGWRK 
SKGKKEEEKV KEEEEVMVVP KFVGEGSSDK EWCPPSDPDF SMYVYEVTKS ILPITNIKEQ 
IEDLAKYVAE KMGGKIPKEK LPDFSWELHI SELKFQLKSN VIPIGHVKKG IFYHRALLFK 
ALADRIGIGC SLVRGEYGRA WNEVMLQNDS RKGVIGGLPA PEMYVIDLMF HPGGLMKLRS 
READLYRFI