PRDM6

protein-coding

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

Gene summary

The protein encoded by this gene is a transcriptional repressor and a member of the PRDM family. Family members contain a PR domain and multiple zinc-finger domains. The encoded protein is involved in regulation of vascular smooth muscle cells (VSMC) contractile proteins. Mutations in this gene result in patent ductus arteriosus 3 (PDA3). [provided by RefSeq, Apr 2017]

MANE transcript

NM_001136239.4

Inheritance

ClinVar variants

P:2U:121B:37

Top phenotype

Patent ductus arteriosus 3

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr5:123,089,241-123,194,266

External References & Databases

Ensembl (ENSG00000061455)

Transcript & Mutation Effects

hg38 • Region Span ~105.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

patent ductus arteriosus 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0024266

Submitter: Labcorp Genetics (formerly Invitae)

patent ductus arteriosus 3STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0024266

Submitter: PanelApp Australia

familial patent arterial ductSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018758

Submitter: Orphanet

patent ductus arteriosus 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0024266

Submitter: G2P

Clinical Genomic Database (CGD)

Patent ductus arteriosus 3AD

Manifestation: Cardiovascular

Intervention: Cardiovascular

Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management

Refs: 4284236; 27181681

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRDM6 variants in ClinVar

8 Conditions Cataloged

Inborn genetic diseasesTotal: 117

not specifiedTotal: 32

not providedTotal: 14

PRDM6-related disorderTotal: 12

Patent ductus arteriosus 3Total: 11

Familial patent arterial ductTotal: 1

Congenital heart diseaseTotal: 1

Congenital anomaly of kidney and urinary tractTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001136239.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				22 clinvar	1 clinvar	23
missense	2 clinvar		121 clinvar	12 clinvar	1 clinvar	136
nonsense						0
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)						0
Total	2	0	121	34	3	160

Highest pathogenic variant AF is 7.1475233e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001136239.4	RefSeq	NP_001129711.1	7	MANE Select
ENST00000407847.5	Ensembl	ENSP00000384725.3	7	MANE Select
ENST00000434521.1	Ensembl	ENSP00000390919.1	2	Standard
ENST00000890813.1	Ensembl	ENSP00000560872.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysine degradation - Homo sapiens (human)

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

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

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000407847
Coding exons: 7
Length: 105145
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.13	228	281	0.810	0.0000150	3795
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.0986

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.157

Gene Damage Prediction

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