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
Phenotypes
GenCC
Source:
- left ventricular noncompaction 8 (Moderate), mode of inheritance: AD
- dilated cardiomyopathy (Strong), mode of inheritance: AD
- left ventricular noncompaction 8 (Moderate), mode of inheritance: AD
- left ventricular noncompaction 8 (Limited), mode of inheritance: AD
- familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
- left ventricular noncompaction (Supportive), 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 (1270 variants)
- not_provided (444 variants)
- not_specified (196 variants)
- Inborn_genetic_diseases (168 variants)
- PRDM16-related_disorder (58 variants)
- Primary_dilated_cardiomyopathy (5 variants)
- Wolff-Parkinson-White_pattern (4 variants)
- Left_ventricular_noncompaction_cardiomyopathy (4 variants)
- Cardiomyopathy,_dilated,_1LL (3 variants)
- Familial_restrictive_cardiomyopathy (2 variants)
- Microcephaly (1 variants)
- See_cases (1 variants)
- Cardiac_arrhythmia (1 variants)
- PRDM16-related_congenital_heart_disease (1 variants)
- Primary_familial_hypertrophic_cardiomyopathy (1 variants)
- Cerebellar_dysfunction_with_variable_cognitive_and_behavioral_abnormalities (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. These statistics are base on transcript: NM_000022114.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 11 | 408 | 13 | 432 | ||
| missense | 1 | 670 | 63 | 3 | 737 | |
| nonsense | 4 | 4 | 9 | 17 | ||
| start loss | 0 | |||||
| frameshift | 4 | 4 | 22 | 30 | ||
| splice donor/acceptor (+/-2bp) | 1 | 2 | 8 | 11 | ||
| Total | 10 | 10 | 720 | 471 | 16 |
Highest pathogenic variant AF is 0.0000013687511
Loading clinvar variants...
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 |
|---|---|---|---|---|---|---|
| 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
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 |
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