PRDM16

PR/SET domain 16, the group of Zinc fingers C2H2-type|MicroRNA protein coding host genes|Lysine methyltransferases|PR/SET domain family

Basic information

Region (hg38): 1:3069168-3438621

Links

ENSG00000142611 ∙ NCBI:63976 ∙ OMIM:605557 ∙ HGNC:14000 ∙ Uniprot:Q9HAZ2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• left ventricular noncompaction 8 (Moderate), mode of inheritance: AD
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• left ventricular noncompaction (Supportive), mode of inheritance: AD
• left ventricular noncompaction 8 (Moderate), mode of inheritance: AD
• left ventricular noncompaction 8 (Limited), mode of inheritance: AD
• dilated cardiomyopathy (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated, ILL; Left ventricular noncompaction 8	AD	Cardiovascular	Individuals have been described as manifesting with findings such as arrhythmias, cardiac valvular abnormalities, and dilated cardiomyopathy, and surveillance (eg, with echocardiogram and electrocardiogram) may allow early medical and/or surgical interventions (eg, intracardiac defibrillator) may be beneficial in terms of reducing disease-associated morbidity and mortality	Cardiovascular	18506004; 21551322; 23768516

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRDM16 gene.

• Left ventricular noncompaction 8 (3 variants)
• Left ventricular noncompaction cardiomyopathy (3 variants)
• not provided (2 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 PRDM16 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			4	337	15	356
missense			505	25	2	532
nonsense	3	2	6			11
start loss						0
frameshift	3	4	14			21
inframe indel			15	1		16
splice donor/acceptor (+/-2bp)			6			6
splice region			13	27	2	42
non coding			5	147	59	211
Total	6	6	555	510	76

Variants in PRDM16

This is a list of pathogenic ClinVar variants found in the PRDM16 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-3069243-T-C		not specified	Likely benign (Apr 24, 2017)
1-3069246-C-A		not specified	Benign/Likely benign (Aug 19, 2023)
1-3069264-G-A		Left ventricular noncompaction 8	Uncertain significance (Nov 27, 2020)
1-3069264-G-C			Uncertain significance (May 27, 2022)
1-3069280-G-A		Left ventricular noncompaction 8	Likely benign (Nov 04, 2021)
1-3069287-C-T		Left ventricular noncompaction 8	Likely benign (Sep 25, 2020)
1-3069289-A-G		Left ventricular noncompaction 8	Likely benign (Sep 10, 2023)
1-3069313-CGGCCGCGCCGCGCCGCCGGGGCCCGGGCCGCCG-C		Left ventricular noncompaction 8	Likely benign (Jun 11, 2022)
1-3069321-C-G			Benign (Jun 15, 2018)
1-3069544-T-TC			Likely benign (Dec 03, 2020)
1-3185810-C-T			Likely benign (Aug 14, 2018)
1-3185956-C-A			Likely benign (Jun 16, 2018)
1-3186088-C-T			Likely benign (Aug 14, 2018)
1-3186105-C-A		Left ventricular noncompaction 8	Likely benign (Apr 29, 2022)
1-3186105-C-T		Left ventricular noncompaction 8	Likely benign (Oct 04, 2023)
1-3186106-G-A		Left ventricular noncompaction 8	Likely benign (May 22, 2023)
1-3186110-C-T		not specified • Left ventricular noncompaction 8	Benign (Jan 28, 2024)
1-3186111-G-A		not specified • Left ventricular noncompaction 8	Conflicting classifications of pathogenicity (Nov 27, 2023)
1-3186126-T-C		Left ventricular noncompaction 8	Conflicting classifications of pathogenicity (Oct 05, 2023)
1-3186129-C-T		Left ventricular noncompaction 8	Likely benign (Aug 23, 2023)
1-3186130-G-A			Uncertain significance (Aug 16, 2017)
1-3186135-C-T		Left ventricular noncompaction 8	Likely benign (May 11, 2018)
1-3186135-CGTT-C		Left ventricular noncompaction 8	Uncertain significance (Jun 21, 2018)
1-3186136-G-A		Left ventricular noncompaction 8 • not specified • PRDM16-related disorder	Likely benign (Jan 26, 2024)
1-3186136-G-T		Left ventricular noncompaction 8	Uncertain significance (Sep 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRDM16	protein_coding	protein_coding	ENST00000270722	17	369454

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000148	124788	0	4	124792	0.0000160

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.35	745	856	0.870	0.0000586	8369
Missense in Polyphen		169	257.45	0.65645		2528
Synonymous	-1.64	447	405	1.10	0.0000335	2547
Loss of Function	5.95	4	48.9	0.0817	0.00000242	571

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.0000177	0.0000177
Middle Eastern	0.0000556	0.0000556
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds DNA and functions as a transcriptional regulator. Functions in the differentiation of brown adipose tissue (BAT) which is specialized in dissipating chemical energy in the form of heat in response to cold or excess feeding while white adipose tissue (WAT) is specialized in the storage of excess energy and the control of systemic metabolism. Together with CEBPB, regulates the differentiation of myoblastic precursors into brown adipose cells. Functions also as a repressor of TGF-beta signaling. Isoform 4 may regulate granulocytes differentiation. {ECO:0000269|PubMed:12816872, ECO:0000269|PubMed:14656887, ECO:0000269|PubMed:19049980}.
• Disease: DISEASE: Cardiomyopathy, dilated 1LL (CMD1LL) [MIM:615373]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:23768516}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=A chromosomal aberration involving PRDM16 is found in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Reciprocal translocation t(1;3)(p36;q21). Isoform 4 is specifically expressed in adult T-cell leukemia. {ECO:0000269|PubMed:11050005, ECO:0000269|PubMed:12557231}.
• Pathway: Thermogenesis - Homo sapiens (human);Differentiation of white and brown adipocyte;FTO Obesity Variant Mechanism;PKMTs methylate histone lysines;Chromatin modifying enzymes;Chromatin organization (Consensus)

Recessive Scores

• pRec: 0.191

Intolerance Scores

• loftool: 0.101
• rvis_EVS: -1.42
• rvis_percentile_EVS: 4.06

Haploinsufficiency Scores

• pHI: 0.356
• hipred: Y
• hipred_score: 0.774
• ghis: 0.499

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.594

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Prdm16
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland 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); growth/size/body region phenotype; craniofacial phenotype; cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; respiratory system phenotype; liver/biliary system 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); normal phenotype; hematopoietic system phenotype; 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); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: prdm16
• Affected structure: cardiac muscle cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;neurogenesis;negative regulation of transforming growth factor beta receptor signaling pathway;histone lysine methylation;somatic stem cell population maintenance;regulation of cellular respiration;tongue development;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;white fat cell differentiation;brown fat cell differentiation;roof of mouth development;positive regulation of brown fat cell differentiation;positive regulation of cold-induced thermogenesis
• Cellular component: nucleus;nucleoplasm;cytosol;aggresome;transcriptional repressor complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;transcription coactivator activity;protein binding;histone-lysine N-methyltransferase activity;activating transcription factor binding;sequence-specific DNA binding;SMAD binding;metal ion binding