Neuropathy, Hereditary Sensory and Autonomic, Type VIII (PRDM12)
Dred_ID | RD00015 |
OMIM ID | 616488 |
Disease name | Neuropathy, Hereditary Sensory and Autonomic, Type VIII |
Alternative names | HSAN8 |
Category | Genetic diseases, Neuronal diseases, Rare diseases, Eye diseases, Skin diseases, Gastrointestinal diseases, Metabolic diseases, Ear diseases, Mental diseases |
Phenotype | OMIM: Hereditary sensory and autonomic neuropathy type VIII is an autosomal recessive neurologic disorder characterized by congenital insensitivity to pain resulting in ulceration to the fingers, tongue, lips, and other distal appendages. Affected individuals may also have decreased sweating and tear production (summary by Chen et al., 2015). |
Miscellaneouse | OMIM: onset in first months of life |
Prevalence | <1/1000000 (Worldwide) [source: MalaCards] |
Inheritance | Autosomal recessive |
Anticipation | Yes |
Evidence | Strong |
Gene symbol | PRDM12 |
Alias symbols | PFM9; HSAN8 |
Gene name | PR/SET domain 12 |
Gene map locus | 9q34.12; chr9:130,664,594-130,682,986(+) |
Ensembl Gene ID | ENSG00000130711 |
Gene expression and Gene Ontology | BioGPS |
Protein expression | Human Protein Atlas |
Gene sequence | Sequence |
Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
Gene Description | This gene encodes a transcriptional regulator of sensory neuronal specification that plays a critical role in pain perception. The encoded protein contains an N-terminal PRDI-BF1 and RIZ homology (PR) domain, a SET domain, and three C-terminal C2H2 zinc finger DNA-binding domains. Naturally occurring mutations in this gene are associated with congenital insensitivity to pain (CIP), and hereditary sensory and autonomic neuropathies (HSAN's) affecting peripheral sensory and autonomic neurons. Deregulation of this gene is associated with solid cancers and hematological malignancies including chronic myeloid leukaemia. [provided by RefSeq, Mar 2017] |
Repeat unit | GCC |
Normal repeat copies | 12 |
Pathogenic repeat copies | ≥18 |
Gene | PRDM12 |
Repeat location | CDS |
Chromosome locus | chr9:130681607-130681642 (+) |
Repeat conservation | Repeat Conservation from UCSC Genome Browser |
Toxic cause | Protein |
Possible toxicity | Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal. New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP). Here we identified 10 different homozygous mutations in PRDM12 (encoding PRDI-BF1 and RIZ homology domain-containing protein 12) in subjects with CIP from 11 families. Prdm proteins are a family of epigenetic regulators that control neural specification and neurogenesis. We determined that Prdm12 is expressed in nociceptors and their progenitors and participates in the development of sensory neurons in Xenopus embryos. Moreover, CIP-associated mutants abrogate the histone-modifying potential associated with wild-type Prdm12. Prdm12 emerges as a key factor in the orchestration of sensory neurogenesis and may hold promise as a target for new pain therapeutics. [By PMID: 26005867] |
Pathway annotation | Reactome, KEGG |
PMID | 26005867 |
Authors | Chen YC, Auer-Grumbach M, Senderek J |
Title | Transcriptional regulator PRDM12 is essential for human pain perception |
Journal | Nature Genetics |
Year | 2015 |