Neuropathy, Hereditary Sensory and Autonomic, Type VIII (PRDM12)


Dred_IDRD00015
OMIM ID616488
Disease nameNeuropathy, Hereditary Sensory and Autonomic, Type VIII
Alternative namesHSAN8
CategoryGenetic diseases, Neuronal diseases, Rare diseases, Eye diseases, Skin diseases, Gastrointestinal diseases, Metabolic diseases, Ear diseases, Mental diseases
PhenotypeOMIM: 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).
MiscellaneouseOMIM: onset in first months of life
Prevalence<1/1000000 (Worldwide) [source: MalaCards]
InheritanceAutosomal recessive
AnticipationYes
EvidenceStrong
Gene symbolPRDM12
Alias symbolsPFM9; HSAN8
Gene namePR/SET domain 12
Gene map locus9q34.12; chr9:130,664,594-130,682,986(+)
Ensembl Gene IDENSG00000130711
Gene expression and Gene OntologyBioGPS
Protein expressionHuman Protein Atlas
Gene sequenceSequence
VariationClinVar,  dbSNP
Gene conservationGene Conservation from UCSC Genome Browser
Gene DescriptionThis 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 unitGCC
Normal repeat copies12
Pathogenic repeat copies≥18
GenePRDM12
Repeat locationCDS
Chromosome locuschr9:130681607-130681642 (+)
Repeat conservationRepeat Conservation from UCSC Genome Browser
Toxic causeProtein
Possible toxicityPain 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 annotationReactome, KEGG
PMID26005867
AuthorsChen YC, Auer-Grumbach M, Senderek J
TitleTranscriptional regulator PRDM12 is essential for human pain perception
JournalNature Genetics
Year2015


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Data collected by OmicsLab, IGDB, CAS. All rights reserved.