ACR
protein-codingacrosin
Gene summary
Acrosin is the major proteinase present in the acrosome of mature spermatozoa. It is a typical serine proteinase with trypsin-like specificity. It is stored in the acrosome in its precursor form, proacrosin. The active enzyme functions in the lysis of the zona pellucida, thus facilitating penetration of the sperm through the innermost glycoprotein layers of the ovum. The mRNA for proacrosin is synthesized only in the postmeiotic stages of spermatogenesis. In humans proacrosin first appears in the haploid spermatids. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: Genitourinary
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ACR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001097.3. 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 | 70 | 5 | 1 | 76 | ||
| nonsense | 1 | 1 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 0 | 71 | 6 | 2 | 80 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001088.2 | 5 | MANE Select | |
| Ensembl | ENSP00000216139.5 | 5 | MANE Select | |
| Ensembl | ENSP00000435120.1 | 4 | Standard | |
| Ensembl | ENSP00000435120.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fertilization
- Reproduction
- Acrosome Reaction
Biological Process
- acrosome matrix dispersal
- activation of adenylate cyclase activity
- single fertilization
- binding of sperm to zona pellucida
- acrosome reaction
Molecular Function
- protease binding
- DNA binding
- amidase activity
- serine-type endopeptidase activity
- copper ion binding
Cellular Component
- extracellular region
- nucleus
- Golgi-associated vesicle
- protein-containing complex
- acrosomal matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000216139
- Coding exons
- 5
- Length
- 7139
- Individuals with no LoFs
- 125734
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 125747
- p
- 0.0000517
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.447 | 215 | 234 | 0.918 | 0.0000145 | 2661 |
| Missense (PolyPhen) | 61 | 93.306 | 0.65376 | 971 | ||
| Synonymous | -2.34 | 129 | 99.3 | 1.30 | 0.00000695 | 907 |
| Loss of Function | 1.86 | 5 | 11.9 | 0.419 | 6.08e-7 | 130 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acrosin is the major protease of mammalian spermatozoa. It is a serine protease of trypsin-like cleavage specificity, it is synthesized in a zymogen form, proacrosin and stored in the acrosome.;
Recessive Scores
- pRec
- 0.260
Intolerance Scores
- LoFtool
- 0.267
- RVIS EVS
- -0.6
- RVIS percentile EVS
- 17.91
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.365
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |