HINT2

Chr 9

histidine triad nucleotide binding protein 2

Also known as: HIT-17

NCBI Gene: 84681ENSG00000137133UniProt: Q9BX68

Histidine triad proteins, such as HINT2, are nucleotide hydrolases and transferases that act on the alpha-phosphate of ribonucleotides (Brenner, 2002 [PubMed 12119013]).[supplied by OMIM, Mar 2008]

0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HINT2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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.
1.72LOEUF
pLI 0.000
Z-score -0.01
OE 1.00 (0.58–1.72)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.35Z-score
OE missense 1.11 (0.94–1.31)
95 obs / 85.8 exp
Tolerant

Tolerant to missense variation

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.1.00 (0.58–1.72)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (0.94–1.31)
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.0.89
0≤1.21.6
LoF obs/exp: 8 / 8.0Missense obs/exp: 95 / 85.8Syn Z: 0.47

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

HINT2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
HINT2 may be One Clinical Significance Target for Patient with Diabetes Mellitus and Reduced ROS-Induced Oxidative Stress and Ferroptosis by MCU.
Bai M et al.·Horm Metab Res
2024
The histidine triad nucleotide-binding protein 2 (HINT-2) positively regulates hepatocellular energy metabolism.
Rajasekaran R et al.·FASEB J
2018
Histidine triad nucleotide-binding protein 2: From basic science to clinical implications.
Yao J et al.·Biochem Pharmacol
2023Review
HINT2 downregulation promotes colorectal carcinoma migration and metastasis.
Li W et al.·Oncotarget
2017
Clinical significance of down-regulated HINT2 in hepatocellular carcinoma.
Zhou DK et al.·Medicine (Baltimore)
2019
Prognosis prediction and drug guidance of ovarian serous cystadenocarcinoma through mitochondria gene-based model.
Shen D et al.·Cancer Genet
2025Functional
Biochemical and biophysical characterization, and 3D structure modeling of human HINT3, a hydrolase of the HIT superfamily.
Dolot R et al.·Bioorg Chem
2025Functional
Computer-determined dosage of insulin in the management of neonatal hyperglycaemia (HINT2): protocol of a randomised controlled trial.
Alsweiler J et al.·BMJ Open
2017
The influence of mitochondrial biological function on sudden sensorineural hearing loss: Exploring potential mechanisms and associations through Mendelian randomization analysis.
Chen J et al.·Medicine (Baltimore)
2025Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Acetylation of Hint2 mitigates acute liver failure by suppressing neutrophil chemotaxis and NETosis through maintaining mitochondrial calcium and protein homeostasis.
Guo J et al.·Int Immunopharmacol
2026
From virtual screening to functional discovery: Apigenin ameliorates acute pancreatitis by targeting HINT2 to regulate the mitochondrial acetylome.
Peng Y et al.·Phytomedicine
2026Functional
HINT2-Mediated Mitochondrial Modulation Contributes to G-CSF Neuroprotection in Alcohol Use Disorder-Related Ischemic Stroke.
Guo ZC et al.·Mol Neurobiol
2025
Targeting the HDAC6/Hint2/MICU1 axis to ameliorate acute liver failure via inhibiting NETosis.
Guo J et al.·Life Sci
2025
Genetic and pharmacological targeting of HINT2 promotes OXPHOS to alleviate inflammatory responses and cell necrosis in acute pancreatitis.
Yao J et al.·Pharmacol Res
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools