ADAM2
protein-codingADAM metallopeptidase domain 2, the group of ADAM metallopeptidase domain containing
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 encoded protein is a subunit of an integral sperm membrane glycoprotein called fertilin, which plays an important role in sperm-egg interactions. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]
- FTNB
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~94.5 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 ADAM2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001464.5. 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 | 0 | |||||
| missense | 101 | 7 | 108 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 103 | 7 | 0 | 110 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001455.3 | 20 | MANE Select | |
| Ensembl | ENSP00000265708.4 | 20 | MANE Select | |
| RefSeq | NP_001265042.1 | 19 | Standard | |
| RefSeq | NP_001265043.1 | 19 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Interaction With The Zona Pellucida
- Fertilization
- Reproduction
- Alpha9 beta1 integrin signaling events
Biological Process
- proteolysis
- cell adhesion
- binding of sperm to zona pellucida
- fusion of sperm to egg plasma membrane involved in single fertilization
- visual learning
Molecular Function
- metalloendopeptidase activity
- integrin binding
- metallopeptidase activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- cell surface
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000265708
- Coding exons
- 20
- Length
- 94555
- Individuals with no LoFs
- 125279
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 467
- Defined
- 125747
- p
- 0.00186
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.651 | 413 | 377 | 1.09 | 0.0000184 | 4851 |
| Missense (PolyPhen) | 97 | 95.141 | 1.0195 | 1273 | ||
| Synonymous | -1.08 | 147 | 131 | 1.12 | 0.00000705 | 1268 |
| Loss of Function | 0.645 | 36 | 40.4 | 0.890 | 0.00000170 | 577 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.015 | 0.015 | notable |
| Latino/Admixed American | 0.0022 | 0.0022 | notable |
| Ashkenazi Jewish | 0.00041 | 0.00040 | rare |
| East Asian | 0.00075 | 0.00071 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00085 | 0.00084 | rare |
| South Asian | 0.0011 | 0.0010 | notable |
| Other | 0.00099 | 0.00098 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Sperm surface membrane protein that may be involved in sperm-egg plasma membrane adhesion and fusion during fertilization. Could have a direct role in sperm-zona binding or migration of sperm from the uterus into the oviduct. Interactions with egg membrane could be mediated via binding between its disintegrin-like domain to one or more integrins receptors on the egg. This is a non catalytic metalloprotease-like protein.;
Recessive Scores
- pRec
- 0.116
Intolerance Scores
- LoFtool
- 0.573
- RVIS EVS
- 0.87
- RVIS percentile EVS
- 88.87
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.346
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |