HINT1

Chr 5AR

histidine triad nucleotide binding protein 1

Also known as: HINT, NMAN, PKCI-1, PRKCNH1

NCBI Gene: 3094 ENSG00000169567 UniProt: P49773 OMIM: 601314

The HINT1 protein hydrolyzes purine nucleotide phosphoramidates substrates through a histidine triad motif and functions as a tumor suppressor. Mutations cause autosomal recessive neuromyotonia and axonal neuropathy through a dominant-negative mechanism.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a protein that hydrolyzes purine nucleotide phosphoramidates substrates, including AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester, and AMP-NH2. The encoded protein interacts with these substrates via a histidine triad motif. This gene is considered a tumor suppressor gene. In addition, mutations in this gene can cause autosomal recessive neuromyotonia and axonal neuropathy. There are several related pseudogenes on chromosome 7. Several transcript variants have been observed. [provided by RefSeq, Dec 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neuromyotonia and axonal neuropathy, autosomal recessiveMIM #137200

Clinical highlights

Gene-disease validity (ClinGen)

Charcot-Marie-Tooth disease · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.81

LOEUF

LOF

Mechanism· G2P

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GeneReview available — HINT1