ADAM21
protein-codingADAM metallopeptidase domain 21, 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 expression of this gene expression is testis-specific. [provided by RefSeq, May 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~43.3 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 ADAM21 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003813.4. 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 | 1 | 1 | ||||
| missense | 100 | 9 | 109 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 102 | 9 | 0 | 111 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003804.2 | 1 | MANE Select | |
| Ensembl | ENSP00000474385.1 | 1 | MANE Select | |
| Ensembl | ENSP00000506213.1 | 1 | Standard | |
| Ensembl | ENSP00000506213.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Interaction With The Zona Pellucida
- Fertilization
- Reproduction
Biological Process
- proteolysis
- single fertilization
- binding of sperm to zona pellucida
Molecular Function
- metalloendopeptidase activity
- metallopeptidase activity
- metal ion binding
Cellular Component
- plasma membrane
- integral component of membrane
- axon
- neuronal cell body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000603540
- Coding exons
- 1
- Length
- 7749
- Individuals with no LoFs
- 125651
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 96
- Defined
- 125748
- p
- 0.000386
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.311 | 360 | 377 | 0.955 | 0.0000187 | 4767 |
| Missense (PolyPhen) | 86 | 91.087 | 0.94416 | 1245 | ||
| Synonymous | -1.54 | 159 | 136 | 1.17 | 0.00000698 | 1349 |
| Loss of Function | 0.140 | 18 | 18.7 | 0.965 | 8.07e-7 | 263 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00090 | 0.00087 | rare |
| Ashkenazi Jewish | 0.00040 | 0.00040 | rare |
| East Asian | 0.00043 | 0.00038 | rare |
| Finnish | 0.000096 | 0.000092 | rare |
| European (Non-Finnish) | 0.00024 | 0.00024 | rare |
| South Asian | 0.00069 | 0.00069 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be involved in sperm maturation and/or fertilization. May also be involved in epithelia functions associated with establishing and maintaining gradients of ions or nutrients.;
Recessive Scores
- pRec
- 0.0921
Intolerance Scores
- LoFtool
- 0.728
- RVIS EVS
- -0.11
- RVIS percentile EVS
- 45.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- 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 |