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): 1:3069167-3438621
Links
Phenotypes
GenCC
Source:
- 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:
| 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
- Left ventricular noncompaction 8 (968 variants)
- not provided (371 variants)
- not specified (163 variants)
- Inborn genetic diseases (31 variants)
- Primary dilated cardiomyopathy (5 variants)
- PRDM16-related condition (4 variants)
- Left ventricular noncompaction cardiomyopathy (4 variants)
- Wolff-Parkinson-White pattern (3 variants)
- Cardiomyopathy, dilated, 1LL (2 variants)
- Familial restrictive cardiomyopathy (2 variants)
- Microcephaly (1 variants)
- Cerebellar dysfunction with variable cognitive and behavioral abnormalities (1 variants)
- See cases (1 variants)
- PRDM16-related congenital heart disease (1 variants)
- Primary familial hypertrophic cardiomyopathy (1 variants)
- Primary dilated cardiomyopathy;Sudden unexplained death (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 | 316 | 15 | 335 | |||
| missense | 468 | 27 | 497 | |||
| nonsense | 9 | |||||
| start loss | 0 | |||||
| frameshift | 14 | 20 | ||||
| inframe indel | 12 | 13 | ||||
| splice donor/acceptor (+/-2bp) | 6 | |||||
| splice region ? | 12 | 27 | 2 | 41 | ||
| non coding ? | 134 | 59 | 198 | |||
| Total | 5 | 5 | 514 | 478 | 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) | ||
| 1-3069280-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 | Likely benign (Sep 26, 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) | ||
| 1-3186147-T-C | Likely benign (Oct 18, 2023) |
GnomAD
Source:
| 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:
- 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