RINT1

Chr 7AR

RAD50 interactor 1

NCBI Gene: 60561ENSG00000135249UniProt: Q6NUQ1

Involved in regulation of membrane traffic between the Golgi and the endoplasmic reticulum (ER); the function is proposed to depend on its association in the NRZ complex which is believed to play a role in SNARE assembly at the ER. May play a role in cell cycle checkpoint control (PubMed:11096100). Essential for telomere length control (PubMed:16600870)

Primary Disease Associations & Inheritance

Infantile liver failure syndrome 3MIM #618641
AR
223
ClinVar variants
13
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RINT1
🧬
Gene-Disease Validity (ClinGen)
hereditary breast carcinoma · ADRefuted

Refuted — evidence has disproved this relationship

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 122 VUS of 223 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.83LOEUF
pLI 0.000
Z-score 2.49
OE 0.60 (0.44–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.83Z-score
OE missense 0.89 (0.81–0.97)
363 obs / 410.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.60 (0.44–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.81–0.97)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
0≤1.21.6
LoF obs/exp: 27 / 45.1Missense obs/exp: 363 / 410.0Syn Z: -0.48

ClinVar Variant Classifications

223 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic1
VUS122
Likely Benign68
Benign6
Conflicting14
12
Pathogenic
1
Likely Pathogenic
122
VUS
68
Likely Benign
6
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
10
0
12
Likely Pathogenic
1
0
0
0
1
VUS
3
108
11
0
122
Likely Benign
1
7
14
46
68
Benign
0
2
2
2
6
Conflicting
—14
Total71173748223

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RINT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

RINT1-related infantile-onset recurrent acute liver failure and skeletal abnormalities

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Infantile liver failure syndrome 3

MIM #618641

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Disorders of vesicular trafficking presenting with recurrent acute liver failure: NBAS, RINT1, and SCYL1 deficiency.
Peters B et al.·J Inherit Metab Dis
2025Review
RNF39 promotes colorectal cancer progression by driving RINT1 degradation and suppressing ER stress-induced apoptosis.
Chen L et al.·Clin Transl Med
2026
RINT1 deficiency disrupts lipid metabolism and underlies a complex hereditary spastic paraplegia.
Launay N et al.·J Clin Invest
2023
Rare mutations in RINT1 predispose carriers to breast and Lynch syndrome-spectrum cancers.
Park DJ et al.·Cancer Discov
2014
RINT1 Bi-allelic Variations Cause Infantile-Onset Recurrent Acute Liver Failure and Skeletal Abnormalities.
Cousin MA et al.·Am J Hum Genet
2019
Reevaluation of RINT1 as a breast cancer predisposition gene.
Li N et al.·Breast Cancer Res Treat
2016
Expression of RINT1 predicts seizure occurrence and outcomes in patients with low-grade gliomas.
Fan X et al.·J Cancer Res Clin Oncol
2015Cohort
Recurrent acute liver failure and neutropenia caused by a novel homozygous RINT1 variant: a brief report of phenotypic expansion and population-specific findings.
Nuzhnaya Е et al.·Hum Genomics
2025Case report
Germline variants detected by multigene panel testing in patients with suspected hereditary breast cancer.
Togashi Y et al.·Surg Today
2025Cohort
Phenotype and Long-Term Outcome in Recurrent Paediatric Acute Liver Failure: Systematic Review and Individual Participant Data Analysis.
Sutton H et al.·Liver Int
2025Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools