AMPH
protein-codingamphiphysin, the group of N-BAR domain containing
Gene summary
This gene encodes a protein associated with the cytoplasmic surface of synaptic vesicles. A subset of patients with stiff-man syndrome who were also affected by breast cancer are positive for autoantibodies against this protein. Alternate splicing of this gene results in two transcript variants encoding different isoforms. Additional splice variants have been described, but their full length sequences have not been determined. A pseudogene of this gene is found on chromosome 11.[provided by RefSeq, Nov 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~247.7 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 AMPH variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001635.4. 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 | 3 | 5 | 8 | |||
| missense | 80 | 7 | 2 | 89 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 85 | 12 | 2 | 99 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001626.1 | 21 | MANE Select | |
| Ensembl | ENSP00000348602.2 | 21 | MANE Select | |
| RefSeq | NP_647477.1 | 20 | Standard | |
| Ensembl | ENSP00000317441.5 | 20 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fc gamma R-mediated phagocytosis - Homo sapiens (human)
- Endocytosis - Homo sapiens (human)
- Monoamine Transport
- Vesicle-mediated transport
- Membrane Trafficking
Biological Process
- endocytosis
- chemical synaptic transmission
- synaptic vesicle endocytosis
- membrane organization
Molecular Function
- protein binding
- phospholipid binding
Cellular Component
- cytosol
- plasma membrane
- synaptic vesicle
- actin cytoskeleton
- cell junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000356264
- Coding exons
- 21
- Length
- 247863
- Individuals with no LoFs
- 125718
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 30
- Defined
- 125748
- p
- 0.000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.49 | 306 | 389 | 0.787 | 0.0000212 | 4492 |
| Missense (PolyPhen) | 129 | 180.41 | 0.71503 | 2184 | ||
| Synonymous | -0.173 | 152 | 149 | 1.02 | 0.00000904 | 1354 |
| Loss of Function | 3.79 | 16 | 42.7 | 0.374 | 0.00000208 | 503 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May participate in mechanisms of regulated exocytosis in synapses and certain endocrine cell types. May control the properties of the membrane associated cytoskeleton.;
Recessive Scores
- pRec
- 0.191
Intolerance Scores
- LoFtool
- 0.696
- RVIS EVS
- 0.23
- RVIS percentile EVS
- 68.52
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.950
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |