ACR
Chr 22ARacrosin
Also known as: SPGF87
Acrosin is a serine protease that facilitates sperm penetration through the zona pellucida during fertilization by lysing the glycoprotein layers surrounding the ovum. Mutations cause spermatogenic failure with autosomal recessive inheritance. This gene is not highly constrained against loss-of-function variants, consistent with its specialized role in male fertility rather than essential developmental processes.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
262 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 0 | 165 | 0 | 166 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 69 | 9 | 0 | 78 |
Likely Benign | 0 | 5 | 0 | 1 | 6 |
Benign | 0 | 3 | 3 | 0 | 6 |
Conflicting | — | 1 | |||
| Total | 1 | 77 | 178 | 1 | 258 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ACR · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Determine Effectiveness of Anifrolumab In SYstemic Sclerosis (DAISY)
ACTIVE NOT RECRUITINGPain in Inflammatory Joint Diseases
RECRUITINGA Safety and Efficacy Study Evaluating CTX112 in Adult Subjects With Refractory Autoimmune Disease
RECRUITINGA Prospective Randomized Trial of ECP in Subclinical AMR
RECRUITINGPathogenesis of Chronic Kidney Disease Associated With Metabolic Dysfunction- Associated Fatty Liver Disease (MAFLD) and Treatment Response of Oral Semaglutide.
NOT YET RECRUITINGDeveloping Hyperpolarized Gas MRI Signatures to Detect and Manage Acute Cellular Rejection
RECRUITINGDuloxetine Metabolism and Fibromyalgia
RECRUITINGRole of Finerenone in African American Veterans With Diabetic Kidney Disease
NOT YET RECRUITING" TREX1 Gene Mutations and Their Role in Systemic Lupus Erythematosus
RECRUITINGOPtimal Adult Heart Transplant Immunosuppression With MicroRNA Levels
RECRUITINGStudy of Two Doses of Crizanlizumab Versus Placebo in Adolescent and Adult Sickle Cell Disease Patients
ACTIVE NOT RECRUITINGEncompaSSc: Evaluation of MTX-474 in Participants With Diffuse Cutaneous Systemic Sclerosis (dcSSc)
RECRUITINGExternal Resources
Links to major genomics databases and tools