PRDM12

PR/SET domain 12, the group of PR/SET domain family|Zinc fingers C2H2-type

Basic information

Region (hg38): 9:130664594-130682986

Links

ENSG00000130711

∙ NCBI:59335 ∙ OMIM:616458 ∙ HGNC:13997 ∙ Uniprot:Q9H4Q4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

congenital insensitivity to pain-hypohidrosis syndrome (Supportive), mode of inheritance: AR
hereditary sensory and autonomic neuropathy (Definitive), mode of inheritance: AR
congenital insensitivity to pain-hypohidrosis syndrome (Definitive), mode of inheritance: AR
congenital insensitivity to pain-hypohidrosis syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuropathy, hereditary sensory and autonomic, type VIII	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	26005867
Insensitivity to pain can result in injuries and infections

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRDM12 gene.

Congenital_insensitivity_to_pain-hypohidrosis_syndrome (238 variants)
Inborn_genetic_diseases (79 variants)
not_provided (44 variants)
not_specified (3 variants)
PRDM12-related_disorder (3 variants)
Hereditary_sensory_and_autonomic_neuropathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRDM12 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021619.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	74 clinvar		75
missense	5 clinvar	5 clinvar	128 clinvar	5 clinvar		143
nonsense	1 clinvar					1
start loss			2			2
frameshift	3 clinvar	1 clinvar	1 clinvar	1 clinvar		6
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar				2
Total	10	7	132	80	0

Highest pathogenic variant AF is 0.000255447

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRDM12	protein_coding	protein_coding	ENST00000253008	5	18388

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.930	0.0698	123773	18	1703	125494	0.00688

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.67	123	187	0.656	0.00000934	2364
Missense in Polyphen		28	61	0.45902		656
Synonymous	-0.287	85	81.7	1.04	0.00000416	740
Loss of Function	3.07	1	12.9	0.0776	5.51e-7	145

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.103	0.0886
Ashkenazi Jewish	0.000495	0.000398
East Asian	0.00263	0.00212
Finnish	0.00	0.00
European (Non-Finnish)	0.00107	0.000847
Middle Eastern	0.00263	0.00212
South Asian	0.00473	0.00367
Other	0.00354	0.00294

dbNSFP

Source: dbNSFP

Function: FUNCTION: Involved in the positive regulation of histone H3-K9 dimethylation. {ECO:0000269|PubMed:26005867}.;
Disease: DISEASE: Neuropathy, hereditary sensory and autonomic, 8 (HSAN8) [MIM:616488]: A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN8 patients manifest congenital insensitivity to pain resulting in ulceration to the fingers, tongue, lips, and other distal appendages. Some patients may also have decreased sweating and tear production. {ECO:0000269|PubMed:26005867}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Haploinsufficiency Scores

pHI: 0.406
hipred: Y
hipred_score: 0.511
ghis: 0.459

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: H
gene_indispensability_pred: E
gene_indispensability_score: 0.522

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Prdm12
Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype;

Zebrafish Information Network

Gene name: prdm12b
Affected structure: hindbrain interneuron
Phenotype tag: abnormal
Phenotype quality: process quality

Gene ontology

Biological process: regulation of transcription by RNA polymerase II;sensory perception of pain;neurogenesis;neuron projection development;methylation;detection of temperature stimulus involved in sensory perception of pain;positive regulation of histone H3-K9 methylation;positive regulation of histone H3-K9 dimethylation
Cellular component: nucleus
Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;methyltransferase activity;chromatin DNA binding;sequence-specific DNA binding;metal ion binding;histone methyltransferase binding