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 (7 variants)
• Inborn genetic diseases (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				62	2	64
missense	2	1	110	3		116
nonsense	1					1
start loss			2			2
frameshift	3	1	1	1		6
inframe indel		1	15	4	6	26
splice donor/acceptor (+/-2bp)	1					1
splice region			1	12		13
non coding				32	13	45
Total	7	3	128	102	21

Variants in PRDM12

This is a list of pathogenic ClinVar variants found in the PRDM12 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-130664655-T-A		Inborn genetic diseases	Uncertain significance (Jul 22, 2022)
9-130664655-T-C		Inborn genetic diseases	Uncertain significance (Apr 27, 2023)
9-130664659-G-A			Uncertain significance (Dec 07, 2023)
9-130664661-G-T		Congenital insensitivity to pain-hypohidrosis syndrome	Uncertain significance (Dec 10, 2020)
9-130664669-C-T		Congenital insensitivity to pain-hypohidrosis syndrome	Uncertain significance (Sep 19, 2022)
9-130664673-C-T		Congenital insensitivity to pain-hypohidrosis syndrome	Uncertain significance (Sep 20, 2021)
9-130664684-C-A		Congenital insensitivity to pain-hypohidrosis syndrome	Uncertain significance (Dec 24, 2021)
9-130664699-G-C		Congenital insensitivity to pain-hypohidrosis syndrome	Uncertain significance (Sep 01, 2021)
9-130664701-G-A		Congenital insensitivity to pain-hypohidrosis syndrome	Likely benign (Apr 20, 2023)
9-130664710-G-T		Congenital insensitivity to pain-hypohidrosis syndrome	Likely benign (Jan 27, 2022)
9-130664711-C-T		Inborn genetic diseases	Uncertain significance (Oct 02, 2023)
9-130664712-C-A		Congenital insensitivity to pain-hypohidrosis syndrome	Uncertain significance (Oct 01, 2021)
9-130664712-C-G		Inborn genetic diseases	Uncertain significance (Apr 23, 2024)
9-130664715-G-A		Congenital insensitivity to pain-hypohidrosis syndrome	Uncertain significance (Apr 30, 2021)
9-130664722-G-C		Congenital insensitivity to pain-hypohidrosis syndrome	Likely benign (Oct 04, 2023)
9-130664723-C-T		Congenital insensitivity to pain-hypohidrosis syndrome	Likely benign (May 10, 2023)
9-130664728-C-A		Congenital insensitivity to pain-hypohidrosis syndrome	Likely benign (Oct 29, 2022)
9-130664731-G-T		Congenital insensitivity to pain-hypohidrosis syndrome	Uncertain significance (Nov 05, 2021)
9-130664734-T-C		Congenital insensitivity to pain-hypohidrosis syndrome	Likely benign (Nov 24, 2023)
9-130664744-G-T		Congenital insensitivity to pain-hypohidrosis syndrome	Pathogenic (Aug 10, 2016)
9-130664746-C-T		Congenital insensitivity to pain-hypohidrosis syndrome	Likely benign (Jul 29, 2023)
9-130664771-C-T		Inborn genetic diseases	Uncertain significance (Mar 22, 2022)
9-130664780-A-G		Congenital insensitivity to pain-hypohidrosis syndrome • Inborn genetic diseases	Uncertain significance (Feb 01, 2024)
9-130664781-A-G		Congenital insensitivity to pain-hypohidrosis syndrome	Uncertain significance (Jun 15, 2022)
9-130664782-CGTGCTCGG-C		Congenital insensitivity to pain-hypohidrosis syndrome	Pathogenic (Jul 08, 2019)

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