AP1M2
protein-codingadaptor related protein complex 1 subunit mu 2, the group of Adaptor related protein complex 1
Gene summary
This gene encodes a subunit of the heterotetrameric adaptor-related protein comlex 1 (AP-1), which belongs to the adaptor complexes medium subunits family. This protein is capable of interacting with tyrosine-based sorting signals. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.6 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 AP1M2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005498.5. 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 | 1 | ||||
| missense | 71 | 1 | 72 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 76 | 2 | 0 | 78 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005489.2 | 12 | MANE Select | |
| Ensembl | ENSP00000250244.5 | 12 | MANE Select | |
| RefSeq | NP_001287816.1 | 12 | Standard | |
| Ensembl | ENSP00000465865.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ap1m2 | Danio rerio | Structure: post-vent region Quality: kinked abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Lysosome - Homo sapiens (human)
- Golgi Associated Vesicle Biogenesis
- Lysosome Vesicle Biogenesis
- Clathrin derived vesicle budding
- Disease
Biological Process
- protein targeting
- vesicle targeting
- antigen processing and presentation of exogenous peptide antigen via MHC class II
- regulation of defense response to virus by virus
Molecular Function
- protein binding
Cellular Component
- Golgi membrane
- lysosomal membrane
- cytosol
- clathrin adaptor complex
- cytoplasmic vesicle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000250244
- Coding exons
- 12
- Length
- 14645
- Individuals with no LoFs
- 125603
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 139
- Defined
- 125742
- p
- 0.000553
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.676 | 223 | 253 | 0.880 | 0.0000154 | 2747 |
| Missense (PolyPhen) | 80 | 102.81 | 0.77812 | 1181 | ||
| Synonymous | -0.589 | 110 | 102 | 1.07 | 0.00000695 | 780 |
| Loss of Function | 1.29 | 15 | 21.5 | 0.699 | 9.81e-7 | 267 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.00041 | 0.00040 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00029 | 0.00022 | rare |
| Finnish | 0.00037 | 0.00037 | rare |
| European (Non-Finnish) | 0.00077 | 0.00076 | rare |
| South Asian | 0.00069 | 0.00069 | rare |
| Other | 0.00050 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the trans-Golgi network (TGN) and endosomes. The AP complexes mediate the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.;
Intolerance Scores
- LoFtool
- 0.755
- RVIS EVS
- -0.87
- RVIS percentile EVS
- 10.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.680
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |