PRDM6

PR/SET domain 6, the group of PR/SET domain family|Zinc fingers C2H2-type|Lysine methyltransferases

Basic information

Region (hg38): 5:123089241-123194266

Links

ENSG00000061455 ∙ NCBI:93166 ∙ OMIM:616982 ∙ HGNC:9350 ∙ Uniprot:Q9NQX0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial patent arterial duct (Supportive), mode of inheritance: AD
• patent ductus arteriosus 3 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Patent ductus arteriosus 3	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular	4284236; 27181681

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRDM6 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRDM6 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				6	2	8
missense			46	2	2	50
nonsense						0
start loss						0
frameshift					1	1
inframe indel				2	2	4
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	46	10	7

Variants in PRDM6

This is a list of pathogenic ClinVar variants found in the PRDM6 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-123090090-C-T		PRDM6-related disorder	Uncertain significance (Jun 08, 2023)
5-123090093-T-C		Inborn genetic diseases	Uncertain significance (Mar 31, 2024)
5-123090099-C-T		Inborn genetic diseases	Uncertain significance (Aug 02, 2021)
5-123090112-G-C		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
5-123090126-A-G		Inborn genetic diseases	Likely benign (Jul 22, 2022)
5-123090135-G-C		Inborn genetic diseases	Uncertain significance (Aug 30, 2022)
5-123090137-G-T		PRDM6-related disorder	Benign (Aug 24, 2020)
5-123090139-G-A		Inborn genetic diseases	Uncertain significance (Sep 07, 2022)
5-123090142-T-C		Inborn genetic diseases	Likely benign (Oct 06, 2021)
5-123090146-G-C		PRDM6-related disorder	Benign (Jul 16, 2019)
5-123090154-C-G		PRDM6-related disorder	Likely benign (May 25, 2024)
5-123090166-A-AGCC		PRDM6-related disorder	Benign (May 02, 2024)
5-123090166-A-AGCCGCC			Likely benign (May 01, 2023)
5-123090171-C-A		Inborn genetic diseases	Uncertain significance (Mar 11, 2022)
5-123090172-C-T		Inborn genetic diseases	Uncertain significance (Jun 26, 2023)
5-123090175-C-T		Inborn genetic diseases	Uncertain significance (Apr 06, 2022)
5-123090180-C-T		Inborn genetic diseases	Uncertain significance (Nov 09, 2023)
5-123090181-C-CG		PRDM6-related disorder	Benign (Dec 31, 2019)
5-123090182-C-G		Inborn genetic diseases	Likely benign (Aug 08, 2023)
5-123090187-C-G		Inborn genetic diseases	Uncertain significance (Aug 16, 2021)
5-123090187-C-T		Inborn genetic diseases	Uncertain significance (Apr 12, 2024)
5-123090189-C-T		Inborn genetic diseases	Uncertain significance (Dec 08, 2023)
5-123090208-C-G		Inborn genetic diseases	Uncertain significance (May 26, 2024)
5-123090213-G-A		Inborn genetic diseases	Uncertain significance (Jul 14, 2021)
5-123090229-G-T		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRDM6	protein_coding	protein_coding	ENST00000407847	7	105145

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.608	0.392	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.13	228	281	0.810	0.0000150	3795
Missense in Polyphen		26	89.571	0.29027		1107
Synonymous	-0.707	129	119	1.08	0.00000692	1230
Loss of Function	3.68	5	24.8	0.202	0.00000148	253

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Putative histone methyltransferase that acts as a transcriptional repressor of smooth muscle gene expression. Promotes the transition from differentiated to proliferative smooth muscle by suppressing differentiation and maintaining the proliferative potential of vascular smooth muscle cells. Also plays a role in endothelial cells by inhibiting endothelial cell proliferation, survival and differentiation. It is unclear whether it has histone methyltransferase activity in vivo. According to some authors, it does not act as a histone methyltransferase by itself and represses transcription by recruiting EHMT2/G9a. According to others, it possesses histone methyltransferase activity when associated with other proteins and specifically methylates 'Lys-20' of histone H4 in vitro. 'Lys-20' methylation represents a specific tag for epigenetic transcriptional repression. {ECO:0000250|UniProtKB:Q3UZD5}.
• Disease: DISEASE: Patent ductus arteriosus 3 (PDA3) [MIM:617039]: A congenital heart defect characterized by the persistent opening of fetal ductus arteriosus that fails to close after birth. Fetal ductus arteriosus connects the pulmonary artery to the descending aorta, allowing unoxygenated blood to bypass the lung and flow to the placenta. Normally, the ductus occludes shortly after birth. {ECO:0000269|PubMed:27181681}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysine degradation - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.0986

Haploinsufficiency Scores

• pHI: 0.322

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.157

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Prdm6
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); respiratory system phenotype; embryo phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;neurogenesis;histone lysine methylation;negative regulation of transcription, DNA-templated;negative regulation of smooth muscle cell differentiation
• 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;histone-lysine N-methyltransferase activity;chromatin DNA binding;protein homodimerization activity;sequence-specific DNA binding;metal ion binding