HYAL2
protein-codinghyaluronidase 2, the group of Hyaluronidases
Gene summary
This gene encodes a weak acid-active hyaluronidase. The encoded protein is similar in structure to other more active hyaluronidases. Hyaluronidases degrade hyaluronan, one of the major glycosaminoglycans of the extracellular matrix. Hyaluronan and fragments of hyaluronan are thought to be involved in cell proliferation, migration and differentiation. Although it was previously thought to be a lysosomal hyaluronidase that is active at a pH below 4, the encoded protein is likely a GPI-anchored cell surface protein. This hyaluronidase serves as a receptor for the oncogenic virus Jaagsiekte sheep retrovirus. The gene is one of several related genes in a region of chromosome 3p21.3 associated with tumor suppression. This gene encodes two alternatively spliced transcript variants which differ only in the 5' UTR.[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 ~5.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0976127
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0976127
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0000358
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Neurologic
Intervention: Audiologic/Otolaryngologic; Cardiovascular
Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; The condition can involve congenital cardiac anomalies, and awareness may allow early management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HYAL2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003773.5. 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 | 6 | 1 | 8 | ||
| missense | 1 | 8 | 80 | 4 | 93 | |
| nonsense | 1 | 1 | 1 | 3 | ||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 3 | 9 | 84 | 10 | 1 | 107 |
Highest pathogenic variant AF is 0.000015491138
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003764.3 | 3 | MANE Select | |
| Ensembl | ENSP00000350387.4 | 3 | MANE Select | |
| RefSeq | NP_149348.2 | 3 | Standard | |
| Ensembl | ENSP00000378571.3 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycosaminoglycan degradation - Homo sapiens (human)
- Hyaluronan uptake and degradation
- Hyaluronan metabolism
- Metabolism of carbohydrates
- Glycosaminoglycan metabolism
Biological Process
- response to reactive oxygen species
- kidney development
- hematopoietic progenitor cell differentiation
- carbohydrate metabolic process
- glycosaminoglycan catabolic process
Molecular Function
- virus receptor activity
- transcription coactivator activity
- hyalurononglucosaminidase activity
- protein binding
- hyaluronic acid binding
Cellular Component
- Golgi membrane
- cytoplasm
- lysosome
- endoplasmic reticulum
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000447092
- Coding exons
- 3
- Length
- 5117
- Individuals with no LoFs
- 125729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125745
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.40 | 248 | 318 | 0.780 | 0.0000216 | 3054 |
| Missense (PolyPhen) | 87 | 125.84 | 0.69136 | 1248 | ||
| Synonymous | -0.790 | 132 | 121 | 1.09 | 0.00000723 | 1009 |
| Loss of Function | 3.06 | 5 | 19.7 | 0.254 | 0.00000112 | 168 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000088 | 0.000088 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hydrolyzes high molecular weight hyaluronic acid to produce an intermediate-sized product which is further hydrolyzed by sperm hyaluronidase to give small oligosaccharides. Displays very low levels of activity. Associates with and negatively regulates MST1R. {ECO:0000269|PubMed:11296287, ECO:0000269|PubMed:12676986, ECO:0000269|PubMed:9712871}.;
Recessive Scores
- pRec
- 0.153
Intolerance Scores
- LoFtool
- 0.536
- RVIS EVS
- -0.42
- RVIS percentile EVS
- 25.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.811
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |