Details for: RINT1

Gene ID: 60561

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: RINT1

Ensembl ID: ENSG00000135249

Description: RAD50 interactor 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • retinal rod cell CL0000604
    CSI 5.35
    rCSI 9.44%
    PRS 88.74
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 5.05
    rCSI 11.5%
    PRS 86.1
  • renal alpha-intercalated cell CL0005011
    CSI 3.7
    rCSI 4.94%
    PRS 94.78
  • alpha-beta T cell CL0000789
    CSI 3.65
    rCSI 4.28%
    PRS 97.76
  • astrocyte of the cerebral cortex CL0002605
    CSI 3.44
    rCSI 7.71%
    PRS 81.59
  • melanocyte CL0000148
    CSI 3.22
    rCSI 2.39%
    PRS 89.5
  • group 3 innate lymphoid cell CL0001071
    CSI 3.05
    rCSI 2.29%
    PRS 94.7
  • vascular leptomeningeal cell CL4023051
    CSI 2.97
    rCSI 5.21%
    PRS 89.52
  • lung ciliated cell CL1000271
    CSI 2.81
    rCSI 3.25%
    PRS 87.61
  • fibroblast of lung CL0002553
    CSI 2.8
    rCSI 2.61%
    PRS 93.59
  • neural crest cell CL0011012
    CSI 2.78
    rCSI 2.2%
    PRS 86.44
  • ciliated epithelial cell CL0000067
    CSI 2.56
    rCSI 2.25%
    PRS 84.61
  • hepatic stellate cell CL0000632
    CSI 2.51
    rCSI 9.4%
    PRS 88.9
  • choroid plexus epithelial cell CL0000706
    CSI 2.49
    rCSI 4.08%
    PRS 86.41
  • stem cell CL0000034
    CSI 2.43
    rCSI 2.34%
    PRS 88.82
  • retinal bipolar neuron CL0000748
    CSI 2.4
    rCSI 4.5%
    PRS 85.16
  • chondrocyte CL0000138
    CSI 2.37
    rCSI 3.77%
    PRS 88.4
  • cerebral cortex endothelial cell CL1001602
    CSI 2.31
    rCSI 4%
    PRS 87.85
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.27
    rCSI 1.53%
    PRS 98.28
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.22
    rCSI 2.66%
    PRS 81.32
  • ependymal cell CL0000065
    CSI 2.05
    rCSI 4.15%
    PRS 76.62
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.87
    rCSI 2.33%
    PRS 79.13
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.59
    rCSI 2.05%
    PRS 82.38
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.51
    rCSI 2.43%
    PRS 82.34
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.45
    rCSI 2.56%
    PRS 80.7
  • retinal ganglion cell CL0000740
    CSI 1.41
    rCSI 3.11%
    PRS 83.35
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.3
    rCSI 2.18%
    PRS 81.38
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.14
    rCSI 2.9%
    PRS 87.47
  • medium spiny neuron CL1001474
    CSI 0.96
    rCSI 8.25%
    PRS 85.32
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.91
    rCSI 2.21%
    PRS 79.21
  • pulmonary alveolar type 1 cell CL0002062
    CSI 0.87
    rCSI 5%
    PRS 90.12
  • blood vessel smooth muscle cell CL0019018
    CSI 0.86
    rCSI 7.03%
    PRS 90.49
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.75
    rCSI 2.34%
    PRS 82.55
  • dopaminergic neuron CL0000700
    CSI 0.73
    rCSI 4.14%
    PRS 82.88
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.69
    rCSI 2.16%
    PRS 84.21
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.62
    rCSI 2.22%
    PRS 79.45
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.6
    rCSI 2.27%
    PRS 81.56
  • direct pathway medium spiny neuron CL4023026
    CSI 0.4
    rCSI 9.65%
    PRS 79.14
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.37
    rCSI 2.17%
    PRS 81.77
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.3
    rCSI 7.29%
    PRS 79.25
  • ON midget ganglion cell CL4033046
    CSI 0.26
    rCSI 5.21%
    PRS 84.85

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 [RINT1](/details-gene/60561), or RAD50 interactor 1, is a protein-coding gene located on chromosome 7q22.3. It plays a crucial dual role in fundamental cellular processes. Primarily, it functions as a key component of the vesicle tethering machinery, mediating retrograde transport from the Golgi apparatus to the endoplasmic reticulum ([Link](https://doi.org/10.1091/mbc.e08-11-1104)). This function is critical for maintaining the integrity of the secretory pathway. Additionally, as its name suggests, [RINT1](/details-gene/60561) interacts with the RAD50 protein and participates in the G2/M DNA damage checkpoint, linking membrane trafficking to genome stability ([Link](https://doi.org/10.1074/jbc.m008893200)). **Overall**, its expression profile shows high significance in a diverse range of metabolically active and structurally complex cells, including [retinal rod cell](/details-cell/CL0000604)s, [ciliated columnar cell of tracheobronchial tree](/details-cell/CL0002145), and [renal alpha-intercalated cell](/details-cell/CL0005011), underscoring its essential role in cellular homeostasis. ## Cellular Roles and Expression Landscape The expression landscape of [RINT1](/details-gene/60561) highlights its importance as a fundamental housekeeping gene, particularly in cells with high demands for protein processing and membrane maintenance. Its highest significance is observed in specialized cell types such as the [retinal rod cell](/details-cell/CL0000604) (CSI: 5.35), which must constantly renew vast photoreceptive outer segment discs, a process heavily reliant on efficient ER-Golgi trafficking. Similarly, high CSI values in secretory epithelial cells like the [ciliated columnar cell of tracheobronchial tree](/details-cell/CL0002145) (CSI: 5.05) and [lung ciliated cell](/details-cell/CL1000271) (CSI: 2.81) are consistent with a role in producing and transporting mucus components. The gene's significance extends to other active cell populations, including [alpha-beta T cell](/details-cell/CL0000789)s (CSI: 3.65) and [group 3 innate lymphoid cell](/details-cell/CL0001071)s (CSI: 3.05), suggesting a role in supporting the robust secretory activity required for immune cell function (e.g., cytokine release). Its presence in neural support cells like [astrocyte of the cerebral cortex](/details-cell/CL0002605) (CSI: 3.44) and mesenchymal cells like [fibroblast of lung](/details-cell/CL0002553) (CSI: 2.80) and [hepatic stellate cell](/details-cell/CL0000632) (CSI: 2.51) further emphasizes its broad importance in maintaining the secretory pathway across diverse lineages. This widespread, yet cell-type-specific, high expression pattern suggests that while [RINT1](/details-gene/60561) is universally required, its function becomes particularly critical in cells defined by high rates of membrane turnover and protein secretion. ## Pathways and Molecular Function Functional annotation data firmly places [RINT1](/details-gene/60561) within the machinery of intracellular membrane dynamics. It is a key participant in [Vesicle-mediated transport](https://reactome.org/content/detail/R-HSA-5653656), specifically in [Copi-dependent golgi-to-er retrograde traffic](https://reactome.org/content/detail/R-HSA-6811434) and the broader process of [Retrograde vesicle-mediated transport, golgi to endoplasmic reticulum](https://www.ebi.ac.uk/QuickGO/term/GO:0006890). This role is critical for recycling SNARE proteins and retrieving ER-resident proteins from the Golgi, thereby maintaining organelle identity and function. Beyond its canonical role in trafficking, [RINT1](/details-gene/60561) is also implicated in the cellular response to DNA damage. Its annotation for [Mitotic g2 dna damage checkpoint signaling](https://www.ebi.ac.uk/QuickGO/term/GO:0007095) is supported by its initial discovery as an interactor of the RAD50 protein, a core component of the MRE11-RAD50-NBS1 (MRN) complex that senses DNA double-strand breaks ([Link](https://doi.org/10.1074/jbc.m008893200)). This dual functionality suggests [RINT1](/details-gene/60561) may act as a coordinator between organellar homeostasis and genome integrity, two processes essential for cell survival and proliferation. ## Research Directions The widespread and essential functions of [RINT1](/details-gene/60561) present several avenues for future investigation, particularly concerning its role in human disease. The finding that bi-allelic mutations in [RINT1](/details-gene/60561) cause infantile-onset acute liver failure and skeletal abnormalities provides a strong clinical link to its fundamental biological roles ([Link](https://doi.org/10.1016/j.ajhg.2019.05.011)). ### Proposed Hypotheses 1. **ER Stress as a Driver of RINT1-Associated Hepatopathy:** Given its function in retrograde trafficking, disease-causing mutations in [RINT1](/details-gene/60561) likely disrupt protein and lipid recycling between the ER and Golgi. We hypothesize that this disruption leads to overwhelming ER stress and activation of the unfolded protein response (UPR) in metabolically active hepatocytes, ultimately triggering apoptosis and causing the observed liver failure. 2. **Cell-Type Specific Vulnerability to RINT1 Dysfunction:** The exceptionally high significance of [RINT1](/details-gene/60561) in [retinal rod cell](/details-cell/CL0000604)s suggests a unique vulnerability in this cell type. We hypothesize that hypomorphic [RINT1](/details-gene/60561) alleles, while insufficient to cause severe systemic disease, could lead to specific retinal dystrophies by impairing the high-volume membrane trafficking required for photoreceptor outer segment renewal. ### Experimental Approach To test the first hypothesis, an *in vitro* disease model could be established. CRISPR-Cas9 genome editing would be used to introduce patient-derived [RINT1](/details-gene/60561) mutations into a human liver cell line (e.g., HepG2) or into induced pluripotent stem cells (iPSCs) subsequently differentiated into hepatocytes. The impact on ER-Golgi trafficking would be assessed by monitoring the localization and processing of reporter cargo proteins. Key markers of ER stress and the UPR (e.g., BiP, CHOP, spliced XBP1) would be quantified by qPCR and Western blotting. Cell viability and apoptosis rates would be measured to directly link the trafficking defect to a cellular phenotype relevant to liver failure. ### Therapeutic Potential Given that [RINT1](/details-gene/60561) is an essential intracellular housekeeping gene, it is not a suitable target for inhibition. Loss of its function is the cause of pathology. Therefore, therapeutic strategies should focus on **restoration of function**. For monogenic diseases like RINT1-deficient liver failure, gene replacement therapy could be a viable long-term strategy. Alternatively, for missense mutations that result in a misfolded but partially active protein, the development of small molecule chaperones designed to stabilize the mutant RINT1 protein could offer a pharmacological approach to ameliorate the trafficking defect and reduce cellular stress.

Genular Protein ID: 2264093958

Symbol: RINT1_HUMAN

Name: RAD50-interacting protein 1

UniProtKB Accession Codes:

Q6NUQ1 Q75MG9 Q75MH0 Q96IW8 Q9H229 Q9HAD9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 1 ExpressionAtlas 1 GO 9 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 2 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11096100

Title: RINT-1, a novel Rad50-interacting protein, participates in radiation-induced G2/M checkpoint control.

PubMed ID: 11096100

DOI: 10.1074/jbc.m008893200

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15029241

Title: Implication of ZW10 in membrane trafficking between the endoplasmic reticulum and Golgi.

PubMed ID: 15029241

DOI: 10.1038/sj.emboj.7600135

PubMed ID: 15272311

Title: Involvement of BNIP1 in apoptosis and endoplasmic reticulum membrane fusion.

PubMed ID: 15272311

DOI: 10.1038/sj.emboj.7600333

PubMed ID: 16600870

Title: The Rb-related p130 protein controls telomere lengthening through an interaction with a Rad50-interacting protein, RINT-1.

PubMed ID: 16600870

DOI: 10.1016/j.molcel.2006.02.016

PubMed ID: 19369418

Title: Identification of the neuroblastoma-amplified gene product as a component of the syntaxin 18 complex implicated in Golgi-to-endoplasmic reticulum retrograde transport.

PubMed ID: 19369418

DOI: 10.1091/mbc.e08-11-1104

PubMed ID: 20462495

Title: Structural analysis of the RZZ complex reveals common ancestry with multisubunit vesicle tethering machinery.

PubMed ID: 20462495

DOI: 10.1016/j.str.2010.02.014

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 24056303

Title: PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex.

PubMed ID: 24056303

DOI: 10.1038/ncb2848

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 31204009

Title: RINT1 bi-allelic variations cause infantile-onset recurrent acute liver failure and skeletal abnormalities.

PubMed ID: 31204009

DOI: 10.1016/j.ajhg.2019.05.011

Sequence Information:

  • Length: 792
  • Mass: 90632
  • Checksum: 6671066FCC5E74D6
  • Sequence:
    • MLPAGEIGAS PAAPCCSESG DERKNLEEKS DINVTVLIGS KQVSEGTDNG DLPSYVSAFI 
EKEVGNDLKS LKKLDKLIEQ RTVSKMQLEE QVLTISSEIP KRIRSALKNA EESKQFLNQF 
LEQETHLFSA INSHLLTAQP WMDDLGTMIS QIEEIERHLA YLKWISQIEE LSDNIQQYLM 
TNNVPEAAST LVSMAELDIK LQESSCTHLL GFMRATVKFW HKILKDKLTS DFEEILAQLH 
WPFIAPPQSQ TVGLSRPASA PEIYSYLETL FCQLLKLQTS DELLTEPKQL PEKYSLPASP 
SVILPIQVML TPLQKRFRYH FRGNRQTNVL SKPEWYLAQV LMWIGNHTEF LDEKIQPILD 
KVGSLVNARL EFSRGLMMLV LEKLATDIPC LLYDDNLFCH LVDEVLLFER ELHSVHGYPG 
TFASCMHILS EETCFQRWLT VERKFALQKM DSMLSSEAAW VSQYKDITDV DEMKVPDCAE 
TFMTLLLVIT DRYKNLPTAS RKLQFLELQK DLVDDFRIRL TQVMKEETRA SLGFRYCAIL 
NAVNYISTVL ADWADNVFFL QLQQAALEVF AENNTLSKLQ LGQLASMESS VFDDMINLLE 
RLKHDMLTRQ VDHVFREVKD AAKLYKKERW LSLPSQSEQA VMSLSSSACP LLLTLRDHLL 
QLEQQLCFSL FKIFWQMLVE KLDVYIYQEI ILANHFNEGG AAQLQFDMTR NLFPLFSHYC 
KRPENYFKHI KEACIVLNLN VGSALLLKDV LQSASGQLPA TAALNEVGIY KLAQQDVEIL 
LNLRTNWPNT GK