HYAL2

hyaluronidase 2, the group of Hyaluronidases

Basic information

Region (hg38): 3:50317790-50322782

Links

ENSG00000068001 ∙ NCBI:8692 ∙ OMIM:603551 ∙ HGNC:5321 ∙ Uniprot:Q12891 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HYAL2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HYAL2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6		6
missense			34	1	2	37
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding				1		1
Total	0	0	34	8	2

Variants in HYAL2

This is a list of pathogenic ClinVar variants found in the HYAL2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-50318139-C-A		Inborn genetic diseases	Uncertain significance (Nov 06, 2023)
3-50318154-G-A		Inborn genetic diseases	Uncertain significance (Dec 04, 2024)
3-50318160-A-T		Inborn genetic diseases	Uncertain significance (Oct 14, 2021)
3-50318200-C-T		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
3-50318278-A-C		HYAL2 deficiency	Pathogenic (Dec 09, 2021)
3-50318278-AGT-A		HYAL2 deficiency • MUGGENTHALER-CHOWDHURY-CHIOZA SYNDROME	Pathogenic (Jan 15, 2025)
3-50318299-T-G			Benign (Jun 09, 2021)
3-50318333-C-G		Inborn genetic diseases	Uncertain significance (Jan 04, 2022)
3-50318351-A-G		HYAL2-related disorder	Likely benign (Feb 26, 2021)
3-50318367-C-T		Inborn genetic diseases	Uncertain significance (Oct 11, 2024)
3-50318387-A-G		HYAL2-related disorder	Likely benign (Apr 01, 2019)
3-50318388-T-C		Inborn genetic diseases	Uncertain significance (Dec 14, 2023)
3-50318416-G-A			Uncertain significance (Mar 08, 2022)
3-50318419-G-A		HYAL2 deficiency • MUGGENTHALER-CHOWDHURY-CHIOZA SYNDROME	Likely pathogenic (Jun 20, 2024)
3-50318427-C-T		Cleft lip and palate-craniofacial dysmorphism-congenital heart defect-hearing loss syndrome	Uncertain significance (Sep 25, 2024)
3-50318439-T-C		Inborn genetic diseases	Uncertain significance (Aug 05, 2024)
3-50318452-G-A		Inborn genetic diseases	Likely benign (Sep 16, 2021)
3-50318481-T-C			Uncertain significance (Mar 08, 2022)
3-50318485-C-T			Uncertain significance (Jun 01, 2023)
3-50318497-C-T		Inborn genetic diseases	Uncertain significance (Mar 28, 2024)
3-50318956-C-T		HYAL2-related disorder	Uncertain significance (Jul 06, 2023)
3-50318974-C-T		HYAL2-related disorder	Likely benign (Jun 16, 2024)
3-50319002-G-A		Inborn genetic diseases	Uncertain significance (Jul 16, 2021)
3-50319004-G-A		HYAL2-related disorder	Likely benign (Sep 30, 2021)
3-50319027-T-C		Inborn genetic diseases	Uncertain significance (Dec 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HYAL2	protein_coding	protein_coding	ENST00000447092	3	5117

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.187	0.813	125729	0	16	125745	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.40	248	318	0.780	0.0000216	3054
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000885	0.0000879
Middle Eastern	0.00	0.00
South Asian	0.000134	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Glycosaminoglycan degradation - Homo sapiens (human);Hyaluronan uptake and degradation;Hyaluronan metabolism;Metabolism of carbohydrates;Glycosaminoglycan metabolism;Metabolism (Consensus)

Recessive Scores

• pRec: 0.153

Intolerance Scores

• loftool: 0.536
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.56

Haploinsufficiency Scores

• pHI: 0.240
• hipred: Y
• hipred_score: 0.703
• ghis: 0.548

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.811

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hyal2
• Phenotype: craniofacial phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype

Gene ontology

• Biological process: response to reactive oxygen species;kidney development;hematopoietic progenitor cell differentiation;carbohydrate metabolic process;glycosaminoglycan catabolic process;response to virus;multicellular organism aging;negative regulation of fibroblast migration;fusion of virus membrane with host plasma membrane;transformation of host cell by virus;hyaluronan catabolic process;negative regulation of cell growth;positive regulation of urine volume;monocyte activation;positive regulation of protein import into nucleus;negative regulation of MAP kinase activity;cellular response to fibroblast growth factor stimulus;positive regulation of transcription by RNA polymerase II;response to antibiotic;viral entry into host cell;skeletal system morphogenesis;positive regulation of inflammatory response;cartilage development;defense response to virus;negative regulation of protein kinase B signaling;multicellular organismal iron ion homeostasis;negative regulation of protein tyrosine kinase activity;renal water absorption;cellular response to interleukin-1;cellular response to tumor necrosis factor;cellular response to UV-B;cellular response to transforming growth factor beta stimulus;positive regulation of interleukin-8 secretion;positive regulation of interleukin-6 secretion;positive regulation of extrinsic apoptotic signaling pathway
• Cellular component: Golgi membrane;cytoplasm;lysosome;endoplasmic reticulum;cytosol;plasma membrane;microvillus;cell surface;apical plasma membrane;endocytic vesicle;anchored component of external side of plasma membrane;cytoplasmic vesicle;membrane raft;anchored component of plasma membrane;perinuclear region of cytoplasm;RNA polymerase II transcription factor complex
• Molecular function: virus receptor activity;transcription coactivator activity;hyalurononglucosaminidase activity;protein binding;hyaluronic acid binding;enzyme binding;receptor signaling protein tyrosine kinase inhibitor activity;receptor tyrosine kinase binding;hyaluronoglucuronidase activity;transforming growth factor beta binding