ADAM8
protein-codingADAM metallopeptidase domain 8, the group of ADAM metallopeptidase domain containing|CD molecules
Gene summary
This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The protein encoded by this gene may be involved in cell adhesion during neurodegeneration, and it is thought to be a target for allergic respiratory diseases, including asthma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.4 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 ADAM8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001109.5. 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 | 25 | 1 | 26 | |||
| missense | 152 | 23 | 3 | 178 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 155 | 48 | 4 | 207 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001100.3 | 23 | MANE Select | |
| Ensembl | ENSP00000453302.1 | 23 | MANE Select | |
| RefSeq | NP_001157961.1 | 21 | Standard | |
| RefSeq | NP_001157962.1 | 20 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| adam8a | Danio rerio | Structure: nucleate erythrocyte Quality: increased accumulation abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neutrophil degranulation
- Extracellular matrix organization
- Innate Immune System
- Immune System
- Degradation of the extracellular matrix
Biological Process
- cell morphogenesis
- angiogenesis
- leukocyte migration involved in inflammatory response
- positive regulation of acute inflammatory response
- proteolysis
Molecular Function
- metalloendopeptidase activity
- serine-type endopeptidase activity
- calcium ion binding
- protein binding
- metallopeptidase activity
Cellular Component
- podosome
- cytoplasm
- plasma membrane
- integral component of plasma membrane
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000445355
- Coding exons
- 23
- Length
- 14466
- Individuals with no LoFs
- 124578
- Homozygous LoFs
- 4
- Heterozygous LoFs
- 897
- Defined
- 125479
- p
- 0.00360
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.380 | 467 | 491 | 0.952 | 0.0000326 | 5210 |
| Missense (PolyPhen) | 186 | 192.94 | 0.96401 | 2104 | ||
| Synonymous | -1.26 | 241 | 217 | 1.11 | 0.0000162 | 1670 |
| Loss of Function | 1.94 | 28 | 41.5 | 0.675 | 0.00000204 | 472 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0014 | 0.0014 | notable |
| Latino/Admixed American | 0.0024 | 0.0023 | notable |
| Ashkenazi Jewish | 0.015 | 0.015 | notable |
| East Asian | 0.0071 | 0.0070 | notable |
| Finnish | 0.00071 | 0.00069 | rare |
| European (Non-Finnish) | 0.0039 | 0.0038 | notable |
| South Asian | 0.0013 | 0.0013 | notable |
| Other | 0.0059 | 0.0057 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Possible involvement in extravasation of leukocytes.;
Recessive Scores
- pRec
- 0.143
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |