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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
RINT1
RAD50 interactor 1
Chromosome 7 Β· 7q22.3
NCBI Gene: 60561Ensembl: ENSG00000135249.9HGNC: HGNC:21876UniProt: Q6NUQ1
89PubMed Papers
21Diseases
0Drugs
42Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingendoplasmic reticulumDsl1/NZR complexmitotic G2 DNA damage checkpoint signalinginfantile liver failure syndrome 3Acute infantile liver failure-multisystemic involvement syndromeFulminant hepatic failurefamilial papillary or follicular thyroid carcinoma
✦AI Summary

RINT1 (RAD50 interactor 1) is a multifunctional protein essential for cellular homeostasis with primary roles in vesicular trafficking and DNA damage response. Functionally, RINT1 regulates membrane traffic between the Golgi and endoplasmic reticulum (ER) through its association with the NRZ complex, facilitating SNARE assembly 1. RINT1 also participates in telomere length control and cell cycle checkpoint signaling through interaction with RAD50, contributing to homologous recombination DNA repair 2. Mechanistically, RINT1 maintains cellular homeostasis by preserving ER-Golgi integrity, regulating SUMOylation pathways, and controlling DNA damage responses 3. Loss of RINT1 function leads to genomic instability, increased endoplasmic reticulum stress, and impaired autophagy 4. Clinically, biallelic RINT1 variants cause infantile liver failure syndrome 3, characterized by recurrent acute liver failure triggered by febrile infections 1. The disease phenotype reflects multi-systemic involvement, including hepatic, skeletal, and nervous system manifestations, with frequency and severity decreasing with age 1. RINT1 deficiency also manifests as hereditary spastic paraplegia with lipid metabolism abnormalities and mitochondrial dysfunction 5. Conversely, elevated RINT1 levels promote colorectal and lung adenocarcinoma progression by suppressing ER stress-induced apoptosis 62, while RINT1 depletion in pancreatic cancer correlates with improved survival 3.

Sources cited
1
RINT1 deficiency causes recurrent acute liver failure (RALF), regulates antegrade and retrograde vesicular trafficking, and leads to multisystemic phenotype with liver, skeletal, and nervous system involvement
PMID: 38279772
2
RINT1 stabilization promotes ER stress-induced apoptosis in colorectal cancer; RNF39 promotes cancer progression by driving RINT1 degradation
PMID: 41457280
3
RINT1 deficiency causes hereditary spastic paraplegia with defective lipid-droplet biogenesis, lipid abnormalities, and mitochondrial dysfunction affecting CNS development
PMID: 37463447
4
BRIP1-mediated RINT1 acetylation strengthens RINT1-RAD50 interaction, facilitates MRE11-RAD50-NBS1 complex assembly, and augments homologous recombination DNA repair in lung adenocarcinoma
PMID: 41740833
5
RINT1 depletion causes DNA double-strand breaks, G2 cell cycle arrest, and defective SUMOylation; low RINT1 expression correlates with better survival in pancreatic cancer
PMID: 33531371
6
Rint1 inactivation triggers genomic instability (chromosome fusion), ER stress, and autophagy inhibition in developing brain
PMID: 26383973
7
RINT1 loss in retinal progenitor cells causes accumulation of endogenous DNA damage and TRP53-mediated apoptosis leading to retinal malformations
PMID: 32850831
8
RINT1 associates with RAD50 and participates in G2 checkpoint control; interacts with ZW10 in vesicle trafficking from Golgi to ER
PMID: 28031358
Disease Associationsβ“˜21
infantile liver failure syndrome 3Open Targets
0.72Strong
Acute infantile liver failure-multisystemic involvement syndromeOpen Targets
0.60Moderate
Fulminant hepatic failureOpen Targets
0.42Moderate
familial papillary or follicular thyroid carcinomaOpen Targets
0.40Weak
papillary thyroid carcinomaOpen Targets
0.40Weak
thyroid cancer, nonmedullary, 1Open Targets
0.40Weak
hereditary spastic paraplegiaOpen Targets
0.37Weak
liver failureOpen Targets
0.37Weak
infantile liver failure syndrome 2Open Targets
0.37Weak
Abnormality of the skeletal systemOpen Targets
0.37Weak
Hepatic failureOpen Targets
0.37Weak
infantile liver failureOpen Targets
0.37Weak
Short statureOpen Targets
0.37Weak
VertigoOpen Targets
0.35Weak
Hereditary breast and ovarian cancer syndromeOpen Targets
0.34Weak
hereditary breast ovarian cancer syndromeOpen Targets
0.34Weak
neurodegenerative diseaseOpen Targets
0.17Weak
familial ovarian cancerOpen Targets
0.15Weak
hereditary neoplastic syndromeOpen Targets
0.12Weak
Inherited cancer-predisposing syndromeOpen Targets
0.12Weak
Infantile liver failure syndrome 3UniProt
Pathogenic Variants42
NM_021930.6(RINT1):c.1107+1G>TLikely pathogenic
not provided|Thyroid cancer, nonmedullary, 1
β˜…β˜…β˜†β˜†2026
NM_021930.6(RINT1):c.1066C>T (p.Gln356Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 356
NM_021930.6(RINT1):c.839C>A (p.Ser280Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 280
NM_021930.6(RINT1):c.1111G>T (p.Glu371Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 371
NM_021930.6(RINT1):c.796del (p.Tyr266fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 266
NM_021930.6(RINT1):c.1207_1210del (p.Asp403fs)Likely pathogenic
Infantile liver failure syndrome 3
β˜…β˜†β˜†β˜†2025β†’ Residue 403
NM_021930.6(RINT1):c.515+2T>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_021930.6(RINT1):c.2021del (p.Phe674fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 674
NM_021930.6(RINT1):c.1828_1829insTT (p.Gln610fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 610
NM_021930.6(RINT1):c.1726_1727del (p.Leu576fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 576
NM_021930.6(RINT1):c.373dup (p.Thr125fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 125
NM_021930.6(RINT1):c.690-2A>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_021930.6(RINT1):c.1501C>T (p.Arg501Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 501
NM_021930.6(RINT1):c.338C>G (p.Ser113Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 113
NM_021930.6(RINT1):c.326del (p.Asn109fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 109
NM_021930.6(RINT1):c.1519G>T (p.Glu507Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 507
NM_021930.6(RINT1):c.1471+1G>TLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_021930.6(RINT1):c.1672-1G>APathogenic
RINT1-related disorder
β˜…β˜†β˜†β˜†2023
NM_021930.6(RINT1):c.1886+1G>TLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_021930.6(RINT1):c.643del (p.Ala215fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 215
View on ClinVar β†—
Related Genes
BNIP1Protein interaction100%NAPAProtein interaction100%ZW10Protein interaction100%SEC22BProtein interaction100%RAB18Protein interaction100%NBASProtein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
57%
Liver
51%
Lung
50%
Ovary
49%
Heart
47%
Gene Interaction Network
Click a node to explore
RINT1BNIP1NAPAZW10SEC22BRAB18NBAS
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q6NUQ1
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.93LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.75 [0.60–0.93]
RankingsWhere RINT1 stands among ~20K protein-coding genes
  • #5,378of 20,598
    Most Researched89
  • #1,488of 5,498
    Most Pathogenic Variants42
  • #8,599of 17,882
    Most Constrained (LOEUF)0.93
Genes detectedRINT1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Disorders of vesicular trafficking presenting with recurrent acute liver failure: NBAS, RINT1, and SCYL1 deficiency.
PMID: 38279772
J Inherit Metab Dis Β· 2025
1.00
2
RNF39 promotes colorectal cancer progression by driving RINT1 degradation and suppressing ER stress-induced apoptosis.
PMID: 41457280
Clin Transl Med Β· 2026
0.90
3
RINT1 deficiency disrupts lipid metabolism and underlies a complex hereditary spastic paraplegia.
PMID: 37463447
J Clin Invest Β· 2023
0.80
4
BRIP1-mediated RINT1 acetylation and NF-ΞΊB activation promote DNA repair and immunosuppressive microenvironment in lung adenocarcinoma.
PMID: 41740833
Cancer Lett Β· 2026
0.70
5
RINT1 Regulates SUMOylation and the DNA Damage Response to Preserve Cellular Homeostasis in Pancreatic Cancer.
PMID: 33531371
Cancer Res Β· 2021
0.60