PRAM1
protein-codingPML-RARA regulated adaptor molecule 1
Gene summary
The protein encoded by this gene is similar to FYN binding protein (FYB/SLAP-130), an adaptor protein involved in T cell receptor mediated signaling. This gene is expressed and regulated during normal myelopoiesis. The expression of this gene is induced by retinoic acid and is inhibited by the expression of PML-RARalpha, a fusion protein of promyelocytic leukemia (PML) and the retinoic acid receptor-alpha (RARalpha). [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PRAM1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032152.5. 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 | 1 | 6 | 2 | 9 | ||
| missense | 122 | 9 | 1 | 132 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 123 | 15 | 3 | 141 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_115528.4 | 10 | MANE Select | |
| Ensembl | ENSP00000408342.2 | 10 | MANE Select | |
| Ensembl | ENSP00000471634.1 | 3 | Standard | |
| Ensembl | ENSP00000550368.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- regulation of transcriptional activity by pml
Biological Process
- integrin-mediated signaling pathway
- regulation of neutrophil degranulation
- T cell receptor signaling pathway
- protein localization to plasma membrane
Molecular Function
- protein binding
- lipid binding
- protein kinase binding
Cellular Component
- plasma membrane
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000423345
- Coding exons
- 10
- Length
- 13057
- Individuals with no LoFs
- 124735
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 46
- Defined
- 124781
- p
- 0.000184
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.107 | 420 | 426 | 0.985 | 0.0000282 | 4252 |
| Missense (PolyPhen) | 115 | 128.12 | 0.89762 | 1488 | ||
| Synonymous | -0.0174 | 200 | 200 | 1.00 | 0.0000153 | 1383 |
| Loss of Function | 2.64 | 10 | 24.0 | 0.417 | 0.00000117 | 296 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00022 | 0.00013 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00018 | 0.00017 | rare |
| Finnish | 0.00015 | 0.000093 | rare |
| European (Non-Finnish) | 0.00022 | 0.00021 | rare |
| South Asian | 0.00039 | 0.00026 | rare |
| Other | 0.00035 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be involved in myeloid differentiation. May be involved in integrin signaling in neutrophils. Binds to PtdIns(4)P.;
Recessive Scores
- pRec
- 0.0941
Intolerance Scores
- RVIS EVS
- 0.78
- RVIS percentile EVS
- 87.24
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.759
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |