ADRM1
protein-codingADRM1 26S proteasome ubiquitin receptor, the group of Proteasome
Gene summary
This gene encodes a member of the adhesion regulating molecule 1 protein family. The encoded protein is a component of the proteasome where it acts as a ubiquitin receptor and recruits the deubiquitinating enzyme, ubiquitin carboxyl-terminal hydrolase L5. Increased levels of the encoded protein are associated with increased cell adhesion, which is likely an indirect effect of this intracellular protein. Dysregulation of this gene has been implicated in carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.8 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 ADRM1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007002.4. 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 | 2 | 3 | 5 | |||
| missense | 57 | 2 | 59 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 64 | 0 | 5 | 69 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_008933.2 | 9 | MANE Select | |
| Ensembl | ENSP00000253003.2 | 9 | MANE Select | |
| RefSeq | NP_001268366.1 | 8 | Standard | |
| RefSeq | NP_001268367.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Epstein-Barr virus infection - Homo sapiens (human)
- Proteasome - Homo sapiens (human)
- Post-translational protein modification
- Metabolism of proteins
- UCH proteinases
Biological Process
- transcription elongation from RNA polymerase II promoter
- ubiquitin-dependent protein catabolic process
- positive regulation of endopeptidase activity
- protein deubiquitination
- proteasome assembly
Molecular Function
- protease binding
- protein binding
- ubiquitin binding
- endopeptidase activator activity
- proteasome binding
Cellular Component
- proteasome complex
- nucleoplasm
- cytosol
- plasma membrane
- proteasome regulatory particle, lid subcomplex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000253003
- Coding exons
- 9
- Length
- 6770
- Individuals with no LoFs
- 118740
- Homozygous LoFs
- 37
- Heterozygous LoFs
- 1313
- Defined
- 120090
- p
- 0.00564
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.38 | 197 | 259 | 0.759 | 0.0000157 | 2616 |
| Missense (PolyPhen) | 23 | 54.204 | 0.42432 | 596 | ||
| Synonymous | -0.743 | 132 | 122 | 1.09 | 0.00000891 | 842 |
| Loss of Function | 3.83 | 0 | 17.1 | 0.00 | 7.37e-7 | 193 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00015 | 0.00014 | rare |
| Latino/Admixed American | 0.044 | 0.040 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00012 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000020 | 0.000019 | rare |
| South Asian | 0.000036 | 0.000034 | rare |
| Other | 0.0035 | 0.0031 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. Within the complex, functions as a proteasomal ubiquitin receptor. Engages and activates 19S-associated deubiquitinases UCHL5 and PSMD14 during protein degradation. UCHL5 reversibly associate with the 19S regulatory particle whereas PSMD14 is an intrinsic subunit of the proteasome lid subcomplex. {ECO:0000269|PubMed:16815440, ECO:0000269|PubMed:16906146, ECO:0000269|PubMed:16990800, ECO:0000269|PubMed:17139257, ECO:0000269|PubMed:18497817, ECO:0000269|PubMed:24752541, ECO:0000269|PubMed:25702870, ECO:0000269|PubMed:25702872}.;
Recessive Scores
- pRec
- 0.117
Intolerance Scores
- RVIS EVS
- 0.06
- RVIS percentile EVS
- 58.85
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.967
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |