SPAM1
protein-codingsperm adhesion molecule 1, the group of Hyaluronidases
Gene summary
Hyaluronidase degrades hyaluronic acid, a major structural proteoglycan found in extracellular matrices and basement membranes. Six members of the hyaluronidase family are clustered into two tightly linked groups on chromosome 3p21.3 and 7q31.3. This gene was previously referred to as HYAL1 and HYA1 and has since been assigned the official symbol SPAM1; another family member on chromosome 3p21.3 has been assigned HYAL1. This gene encodes a GPI-anchored enzyme located on the human sperm surface and inner acrosomal membrane. This multifunctional protein is a hyaluronidase that enables sperm to penetrate through the hyaluronic acid-rich cumulus cell layer surrounding the oocyte, a receptor that plays a role in hyaluronic acid induced cell signaling, and a receptor that is involved in sperm-zona pellucida adhesion. Abnormal expression of this gene in tumors has implicated this protein in degradation of basement membranes leading to tumor invasion and metastasis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~46.2 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 SPAM1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_153189.3. 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 | 55 | 7 | 62 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 56 | 7 | 0 | 63 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_694859.1 | 3 | MANE Select | |
| Ensembl | ENSP00000508393.1 | 3 | MANE Select | |
| RefSeq | NP_001167515.1 | 3 | Standard | |
| RefSeq | NP_001167516.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycosaminoglycan degradation - Homo sapiens (human)
- Interaction With Cumulus Cells
- Fertilization
- chondroitin sulfate degradation (metazoa)
- Reproduction
Biological Process
- carbohydrate metabolic process
- cell adhesion
- binding of sperm to zona pellucida
- fusion of sperm to egg plasma membrane involved in single fertilization
- sperm-egg recognition
Molecular Function
- hyalurononglucosaminidase activity
Cellular Component
- plasma membrane
- anchored component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000340011
- Coding exons
- 4
- Length
- 46183
- Individuals with no LoFs
- 125439
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 23
- Defined
- 125462
- p
- 0.0000917
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.997 | 224 | 270 | 0.829 | 0.0000130 | 3387 |
| Missense (PolyPhen) | 71 | 89.585 | 0.79254 | 1091 | ||
| Synonymous | 1.30 | 77 | 92.9 | 0.829 | 0.00000469 | 964 |
| Loss of Function | 0.729 | 17 | 20.6 | 0.827 | 0.00000110 | 248 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000094 | 0.0000088 | rare |
| South Asian | 0.00069 | 0.00069 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in sperm-egg adhesion. Upon fertilization sperm must first penetrate a layer of cumulus cells that surrounds the egg before reaching the zona pellucida. The cumulus cells are embedded in a matrix containing hyaluronic acid which is formed prior to ovulation. This protein aids in penetrating the layer of cumulus cells by digesting hyaluronic acid. {ECO:0000269|PubMed:8282124}.;
Recessive Scores
- pRec
- 0.122
Intolerance Scores
- LoFtool
- 0.991
- RVIS EVS
- 0.42
- RVIS percentile EVS
- 77.16
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0146
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |