The human genome contains six hyaluronidase like genes. Three of them (HYAL1, HYAL2 and HYAL3) are clustered on chromosome 3p21.3 and the other three (HYAL4, SPAM1 and HYALP1) are clustered on chromosome 7q31.3. Of the three genes on chromosome 7q31.3, HYALP1 is an expressed pseudogene. The extensive homology between the six hyaluronidase genes suggests an ancient gene duplication event before the emergence of modern mammals.

According to Entrez Gene, SPAM1 gene maps to locus NC_000007 and spans a region of 46136 bp. According to Spidey (mRNA to genomic sequence alignment tool), SPAM1 has 7 exons, the sizes being 78, 112, 1160, 90, 441, 99 and 404.

The SPAM1 mRNA has two isoforms; transcript variant 1 (NM_003117) a 2395 bp mRNA and transcript variant 2 (NM_153189) a 2009 bp mRNA. The variant 2 uses an alternate in-frame splice site in the 3 coding region, compared to variant 1, resulting in a shorter C-terminus.
The promoter region of SPAM1 has been shown to contain a CRE (cAMP-responsive element) sequence which is a binding site for CREM (cAMP-responsive element modulator) and thus Spam1 is under a cAMP-dependent transcriptional regulation. No TATA or CCAAT boxes were found in the promoter region of SPAM1. The testis-specific promoters of the human and mouse SPAM1 genes are derived from a sequence that was originally part of an ERV pol gene.

The human SPAM1 pseudogene HYALP1 is located on chromosome 7q31.3.

Two sperm adhesion isoforms exist; one is 511 aa long isoform 1 and the other 509 aa long isoform 2. When the two isoforms are aligned the sequences are 100% identical and no functional difference has been reported.

SPAM1 is a 68 kDa protein that belongs to glycosyl hydrolase 56 family. This family of enzymes has hyaluronidase activity which hydrolyses the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. Sperm hyaluronidase is active at neutral and acidic pHs which results from different active sites in the hyaluronidase domain at the N-terminus of the protein. The hyaluronidase domain also contains a hyaluronic acid (HA) binding site that plays a role in the signaling pathway leading to acrosomal exocytosis. The protein also contains a zona binding domain at the C-terminal end.

According to GNF Expression Atlas 2 Data from U133A and GNF1H Chips, SPAM1 expression is widely limited to testis and epididymis but it was also found to be expressed in murine kidney and female reproductive tract. Both rare and abundant SPAM1 transcripts have been found in neoplastic breast tissue and in a number of other cancers including pharyngeal astatic melanomas and gliomas. In normal somatic cells rare transcripts have been found in breast tissue and in fetal, placental, and prostate cDNA libraries.

SPAM1 is located on the sperm surface and in the lysosome-derived acrosome, where it is bound to the inner acrosomal membrane. The acrosomal membrane SPAM1 differs biochemically from the one on the sperm surface.

SPAM1 is a multifunctional protein; a hyaluronidase that acts in penetrating the cumulus, a receptor for hyaluronic acid induced cell signaling which leads to acrosomal exocytosis and a receptor for the zona pellucida surrounding the oocyte. The zona pellucida recognition function is ascribed to the inner acrosomal membrane SPAM1. The neutral enzyme activity of plasma membrane SPAM1, which is GPI anchored, is responsible for local degradation of the cumulus ECM during sperm penetration. Plasma membrane SPAM1 mediates HA-induced sperm signaling via the HA binding domain. SPAM1 is also secreted by the epithelial cells of the epididymis and has a role in sperm maturation. In addition SPAM1 is implicated in fluid reabsorption and urine concentration in kidney.

- Pan troglodytes sperm adhesion molecule 1 (SPAM1)
- Canis lupus familiaris sperm adhesion molecule 1 (SPAM1)
- Bos taurus sperm adhesion molecule 1 (SPAM1)
- Mus musculus hyaluronoglucosaminidase 5 (Hyal5)
- Mus musculus sperm adhesion molecule 1 (SPAM1)
- Rattus norvegicus sperm adhesion molecule 1 (HYALP_RAT)
- Gallus gallus sperm adhesion molecule 1 (SPAM1)
- Danio rerio sperm adhesion molecule 1 (Spam1)

According to dbSNP, one validated missense SNP for SPAM1 is found in the 47^th aa position causing a V to A (rs34633019) substitution. Other SNPs causing synonymous changes are: rs34404662 A/G substitution at the 3^rd amino acid residue (Val), rs2285996 A/G substitution at the 184^th amino acid residue (Lys) and rs34978112 C/T substitution at the 330^th amino acid residue (Ala). No clinical associations with these SNPs have been reported.

In mice bearing Robertsonian translocation Rb(6.15) and (6.16), reduced Spam1 hyaluronidase activity was found to cause sperm dysfunction. It was proposed that entrapment of spontaneous Spam1 mutations, owing to recombination suppression near the Rb junctions was the major effect.
According to in vitro mutagenesis experiments the following mutations were detected to have functional consequences:
- D146N: 80% loss of activity
- E148Q: loss of activity
- R211G: 90% loss of activity
- E284Q: loss of activity
- R287T: loss of activity