Details for: CCDC138

Gene ID: 165055

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: CCDC138

Ensembl ID: ENSG00000163006

Description: coiled-coil domain containing 138

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • erythroblast CL0000765
    CSI 10.9
    rCSI 28.93%
    PRS 93.36
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 10.19
    rCSI 17.1%
    PRS 82.78
  • mesothelial cell CL0000077
    CSI 9.52
    rCSI 37.25%
    PRS 79.86
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 9.41
    rCSI 29.43%
    PRS 85.53
  • rod bipolar cell CL0000751
    CSI 7.01
    rCSI 12.59%
    PRS 89.03
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 6.22
    rCSI 15.12%
    PRS 80.59
  • blood vessel endothelial cell CL0000071
    CSI 4.12
    rCSI 8.55%
    PRS 91.78
  • retinal bipolar neuron CL0000748
    CSI 4.09
    rCSI 7.65%
    PRS 86.21
  • ependymal cell CL0000065
    CSI 4.04
    rCSI 8.21%
    PRS 77.89
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 3.98
    rCSI 7.02%
    PRS 82.1
  • melanocyte CL0000148
    CSI 3.84
    rCSI 2.84%
    PRS 90.5
  • glial cell CL0000125
    CSI 3.56
    rCSI 13.57%
    PRS 87.75
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.56
    rCSI 4.43%
    PRS 80.54
  • glioblast CL0000030
    CSI 3.51
    rCSI 5.59%
    PRS 86.75
  • GABAergic amacrine cell CL4030027
    CSI 3.45
    rCSI 11.82%
    PRS 82.32
  • neural crest cell CL0011012
    CSI 3.39
    rCSI 2.68%
    PRS 87.57
  • interneuron CL0000099
    CSI 3.34
    rCSI 6.7%
    PRS 88.27
  • cerebellar granule cell CL0001031
    CSI 3.31
    rCSI 4.87%
    PRS 89.09
  • mature T cell CL0002419
    CSI 3.3
    rCSI 2.57%
    PRS 98.1
  • radial glial cell CL0000681
    CSI 3.29
    rCSI 4.57%
    PRS 91.6
  • retinal rod cell CL0000604
    CSI 3.28
    rCSI 5.79%
    PRS 89.65
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 3.2
    rCSI 10.51%
    PRS 83.56
  • amacrine cell CL0000561
    CSI 3.15
    rCSI 9.12%
    PRS 86.09
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 3.15
    rCSI 3.63%
    PRS 86.55
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 3.14
    rCSI 11.3%
    PRS 80.94
  • inhibitory interneuron CL0000498
    CSI 2.97
    rCSI 6.87%
    PRS 85.75
  • neuron CL0000540
    CSI 2.88
    rCSI 7.68%
    PRS 82.88
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.84
    rCSI 3.64%
    PRS 89.91
  • intermediate monocyte CL0002393
    CSI 2.76
    rCSI 4.17%
    PRS 96.19
  • hepatic stellate cell CL0000632
    CSI 2.71
    rCSI 10.14%
    PRS 89.96
  • brush cell of tracheobronchial tree CL0002075
    CSI 2.7
    rCSI 8.02%
    PRS 96.99
  • multi-ciliated epithelial cell CL0005012
    CSI 2.67
    rCSI 2.67%
    PRS 88.1
  • Mueller cell CL0000636
    CSI 2.57
    rCSI 5.87%
    PRS 87.78
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.52
    rCSI 3.01%
    PRS 82.73
  • vascular leptomeningeal cell CL4023051
    CSI 2.5
    rCSI 4.38%
    PRS 90.58
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 2.42
    rCSI 14.24%
    PRS 83.08
  • renal beta-intercalated cell CL0002201
    CSI 2.39
    rCSI 5.7%
    PRS 93.52
  • ciliated epithelial cell CL0000067
    CSI 2.36
    rCSI 2.07%
    PRS 85.66
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 2.35
    rCSI 8.89%
    PRS 82.86
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.35
    rCSI 3.02%
    PRS 83.73
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.25
    rCSI 5.04%
    PRS 82.99
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 2.24
    rCSI 5.79%
    PRS 91.26
  • BEST4+ enteroycte CL4030026
    CSI 2.15
    rCSI 2.67%
    PRS 92.55
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.12
    rCSI 3%
    PRS 91.74
  • cerebral cortex endothelial cell CL1001602
    CSI 2.06
    rCSI 3.56%
    PRS 88.93
  • choroid plexus epithelial cell CL0000706
    CSI 2.03
    rCSI 3.33%
    PRS 87.49
  • lung secretory cell CL1000272
    CSI 2.03
    rCSI 5.03%
    PRS 94.19
  • macroglial cell CL0000126
    CSI 2.01
    rCSI 5.16%
    PRS 89.9
  • neural cell CL0002319
    CSI 1.96
    rCSI 7.4%
    PRS 80.91
  • ciliated cell CL0000064
    CSI 1.94
    rCSI 3.14%
    PRS 87.68
  • H2 horizontal cell CL0004218
    CSI 1.93
    rCSI 9.61%
    PRS 88.57
  • lung ciliated cell CL1000271
    CSI 1.89
    rCSI 2.18%
    PRS 88.54
  • deuterosomal cell CL4033044
    CSI 1.86
    rCSI 6.3%
    PRS 87.88
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 1.8
    rCSI 3.27%
    PRS 87.96
  • epithelial cell of proximal tubule CL0002306
    CSI 1.8
    rCSI 4.39%
    PRS 88
  • parietal epithelial cell CL1000452
    CSI 1.73
    rCSI 4.63%
    PRS 89.14
  • direct pathway medium spiny neuron CL4023026
    CSI 1.7
    rCSI 40.6%
    PRS 80.51
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 1.69
    rCSI 2.04%
    PRS 96.56
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.65
    rCSI 39.92%
    PRS 80.55
  • renal principal cell CL0005009
    CSI 1.63
    rCSI 4.24%
    PRS 93.01
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.59
    rCSI 2.57%
    PRS 83.7
  • GABAergic neuron CL0000617
    CSI 1.59
    rCSI 5.33%
    PRS 81.8
  • retinal ganglion cell CL0000740
    CSI 1.56
    rCSI 3.44%
    PRS 84.58
  • central nervous system neuron CL2000029
    CSI 1.5
    rCSI 11.06%
    PRS 86.65
  • retinal cone cell CL0000573
    CSI 1.5
    rCSI 2.41%
    PRS 86.44
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.48
    rCSI 3.38%
    PRS 86.95
  • medium spiny neuron CL1001474
    CSI 1.48
    rCSI 12.75%
    PRS 86.52
  • neural progenitor cell CL0011020
    CSI 1.43
    rCSI 6.31%
    PRS 83.75
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1.38
    rCSI 3.3%
    PRS 84.67
  • glutamatergic neuron CL0000679
    CSI 1.35
    rCSI 2.77%
    PRS 83.1
  • tissue-resident macrophage CL0000864
    CSI 1.31
    rCSI 6.15%
    PRS 97.52
  • diffuse bipolar 3b cell CL4033030
    CSI 1.25
    rCSI 8.28%
    PRS 88.04
  • diffuse bipolar 6 cell CL4033032
    CSI 1.2
    rCSI 6.32%
    PRS 84.44
  • OFFx cell CL4033036
    CSI 1.16
    rCSI 5.44%
    PRS 84.59
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.09
    rCSI 2.78%
    PRS 88.61
  • H1 horizontal cell CL0004217
    CSI 0.99
    rCSI 3.94%
    PRS 88.11
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.88
    rCSI 2.76%
    PRS 83.8
  • diffuse bipolar 2 cell CL4033028
    CSI 0.82
    rCSI 6.38%
    PRS 86.63
  • ON midget ganglion cell CL4033046
    CSI 0.82
    rCSI 16.74%
    PRS 85.93
  • diffuse bipolar 1 cell CL4033027
    CSI 0.81
    rCSI 6.11%
    PRS 83.71
  • blood vessel smooth muscle cell CL0019018
    CSI 0.73
    rCSI 5.93%
    PRS 91.61
  • flat midget bipolar cell CL4033033
    CSI 0.61
    rCSI 4.37%
    PRS 85.01
  • diffuse bipolar 3a cell CL4033029
    CSI 0.58
    rCSI 3.98%
    PRS 86.03
  • OFF midget ganglion cell CL4033047
    CSI 0.58
    rCSI 11.76%
    PRS 86.59
  • ON parasol ganglion cell CL4033052
    CSI 0.48
    rCSI 6.76%
    PRS 86.84

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

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 [CCDC138](/details-gene/165055) (Coiled-Coil Domain Containing 138) is a protein-coding gene located on chromosome 2q13. The protein product contains a coiled-coil domain, a structural motif known to facilitate protein-protein interactions, which is consistent with its primary molecular function annotation of protein binding ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)). Expression data reveals a unique and highly specific landscape, with [CCDC138](/details-gene/165055) showing prominent significance in distinct and unrelated cell lineages. It is a top marker in hematopoietic progenitors, specifically [erythroblasts](/details-cell/CL0000765), as well as in highly specialized neuronal subtypes, including [lamp5 GABAergic cortical interneurons](/details-cell/CL4023011) and [mesothelial cells](/details-cell/CL0000077). This unusual expression pattern suggests a potentially fundamental, yet context-specific, role that is currently not well understood. The gene was initially identified and characterized through large-scale cDNA and genome sequencing projects ([Link](https://doi.org/10.1038/ng1285), [Link](https://doi.org/10.1038/nature03466)). ## Cellular Roles and Expression Landscape The **Overall** expression profile of [CCDC138](/details-gene/165055) is marked by high significance in a diverse set of specialized cell types, indicating a role that transcends single tissue or system boundaries. Its most significant expression is observed in [erythroblasts](/details-cell/CL0000765) (CSI: 10.90), pointing towards a potential function in erythropoiesis, the process of red blood cell development. Concurrently, [CCDC138](/details-gene/165055) demonstrates high significance across multiple, distinct neuronal populations. These include inhibitory interneurons of the cortex, such as [lamp5 GABAergic cortical interneurons](/details-cell/CL4023011) (CSI: 10.19) and [chandelier pvalb GABAergic cortical interneurons](/details-cell/CL4023036) (CSI: 9.41), as well as neurons of the retina like [rod bipolar cells](/details-cell/CL0000751) (CSI: 7.01). This strong signal in post-mitotic, terminally differentiated neurons suggests a role in maintaining specialized neuronal function or structure. Beyond these two major systems, [CCDC138](/details-gene/165055) is also a significant marker for [mesothelial cells](/details-cell/CL0000077) (CSI: 9.52), which line the body's serous cavities, and [ependymal cells](/details-cell/CL0000065) (CSI: 4.04), which line the cerebral ventricles. Moderate significance is also noted in [blood vessel endothelial cells](/details-cell/CL0000071) (CSI: 4.12) and [glioblasts](/details-cell/CL0000030) (CSI: 3.51). The co-expression in such functionally disparate cells—hematopoietic, neuronal, and epithelial-like—is unusual and suggests that [CCDC138](/details-gene/165055) may be involved in a fundamental cellular process that is particularly important in these specific contexts. ## Pathways and Molecular Function The functional annotation for [CCDC138](/details-gene/165055) is currently limited, reflecting its status as a relatively uncharacterized gene. The primary established molecular function is protein binding ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)). This is strongly supported by its protein architecture, which features a prominent coiled-coil domain. Coiled-coil motifs are well-established mediators of protein-protein oligomerization and serve as structural scaffolds for the assembly of larger protein complexes. The identification of [CCDC138](/details-gene/165055) in phosphoproteomic studies suggests it is expressed at the protein level and may be subject to post-translational regulation ([Link](https://doi.org/10.1021/pr300630k)). However, the specific binding partners of [CCDC138](/details-gene/165055) and the downstream signaling pathways it regulates in cell types like [erythroblasts](/details-cell/CL0000765) or neurons remain to be identified. ## Research Directions The striking expression pattern of [CCDC138](/details-gene/165055) in seemingly unrelated, highly specialized cell types presents a key area for future investigation. The gene's specific function is unknown, leading to several testable hypotheses. 1. **Hypothesis of a Shared Essential Process:** [CCDC138](/details-gene/165055) could function as a scaffolding protein essential for a core cellular process, such as cytoskeletal organization or organelle transport, that is under high demand in both developing [erythroblasts](/details-cell/CL0000765) (e.g., for enucleation) and in maintaining the complex morphology of neurons like [lamp5 GABAergic cortical interneurons](/details-cell/CL4023011). 2. **Hypothesis of Context-Specific Interaction:** Alternatively, [CCDC138](/details-gene/165055) may function as a versatile adaptor protein that binds to different sets of proteins in different cellular contexts. In [erythroblasts](/details-cell/CL0000765), it might associate with factors controlling heme synthesis or membrane remodeling, whereas in neurons, it could interact with synaptic vesicle proteins or components of the dendritic arbor. **Proposed Experiment:** To test the hypothesis of context-specific interactions, a differential proteomics approach could be employed. One could perform immunoprecipitation of endogenous or tagged [CCDC138](/details-gene/165055) from two distinct cellular contexts where it is highly expressed: primary human hematopoietic stem cells differentiated into [erythroblasts](/details-cell/CL0000765), and a relevant neuronal model, such as human iPSC-derived cortical interneurons. The co-precipitated proteins from both cell types would then be identified and quantified using mass spectrometry. This experiment would reveal the interactome of [CCDC138](/details-gene/165055) in each lineage, directly testing whether its binding partners are shared or context-specific. **Therapeutic Potential:** The therapeutic potential of [CCDC138](/details-gene/165055) is currently difficult to assess due to its uncharacterized function. Its high expression in critical cell types like hematopoietic progenitors and neurons suggests that systemic targeting could lead to significant on-target toxicity. However, its noted expression in [glioblasts](/details-cell/CL0000030) might offer a narrow therapeutic window if the gene proves to be essential for tumor cell survival and a specific inhibitor could be developed. Further research into its role in both normal physiology and disease is required before it can be considered a viable therapeutic target.

Genular Protein ID: 1144124742

Symbol: CC138_HUMAN

Name: Coiled-coil domain-containing protein 138

UniProtKB Accession Codes:

Q96M89 Q05DF1 Q4ZG07 Q53TE1 Q6ZUY5 Q86VL7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 2 ExpressionAtlas 1 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 2 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 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: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

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: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

Sequence Information:

  • Length: 665
  • Mass: 76219
  • Checksum: 0723A65295914E82
  • Sequence:
    • MEPRVVKPPG QDLVVESLKS RYGLGGSCPD EYDFSNFYQS KYKRRTLTSP GDLDIYSGDK 
VGSSLKYSDE SKHCRTPLGS LFKHVNVNCL DDELDSFHDL KKQETEEELI ENDYRVSTSK 
ITKQSFKEIE KVALPTNTTS SRPRTECCSD AGDSPLKPVS CPKSKASDKR SLLPHQISQI 
YDELFQIHLK LQCETAAQQK FAEELQKRER FLLEREQLLF RHENALSKIK GVEEEVLTRF 
QIIKEQHDAE VEHLTEVLKE KNKETKRLRS SFDALKELND TLKKQLNEAS EENRKIDIQA 
KRVQARLDNL QRKYEFMTIQ RLKGSSHAVH EMKSLKQEKA PVSKTYKVPL NGQVYELLTV 
FMDWISDHHL SKVKHEESGM DGKKPQLKFA SQRNDIQEKC VKLLPLMTEQ LQWMPFVNIK 
LHEPFVKFIY WSLRQLDAGA QHSTMTSTLR RLGEDIFKGV VTKGIQDNSP QHSVENKPKT 
AAFFKSSNLP LRFLSTLIVL KTVTQADYLA QAFDSLCLDL KTEEGKTLFL EYQAVPVILS 
HLRISSKGLL SNVIDSLLQM TVESKSLQPF LEACSNSLFF RTCSVLLRAP KLDLQILEKL 
SIILQKLSKI KSNKKLFELF TIHLMLQEIQ RTTNPEHAFL CINLNSTLFN LGLTKCNSLV 
SSASP