HYAL2 (hyaluronidase 2)

Gene

• Entrez ID: 8692
• Gene name: Hyaluronidase 2
• Gene symbol: HYAL2
• Synonyms (NCBI Gene): LUCA2, MCCS
• Chromosome: 3
• Chromosome location: 3p21.31
• 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 fragmen

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1057770	hsa-miR-1207-5p	CLIP-seq
MIRT1057771	hsa-miR-1343	CLIP-seq
MIRT1057772	hsa-miR-185	CLIP-seq
MIRT1057773	hsa-miR-3128	CLIP-seq
MIRT1057774	hsa-miR-3154	CLIP-seq
MIRT1057775	hsa-miR-3179	CLIP-seq
MIRT1057776	hsa-miR-3667-3p	CLIP-seq
MIRT1057777	hsa-miR-378g	CLIP-seq
MIRT1057778	hsa-miR-4270	CLIP-seq
MIRT1057779	hsa-miR-4290	CLIP-seq
MIRT1057780	hsa-miR-4306	CLIP-seq
MIRT1057781	hsa-miR-4441	CLIP-seq
MIRT1057782	hsa-miR-4488	CLIP-seq
MIRT1057783	hsa-miR-4644	CLIP-seq
MIRT1057784	hsa-miR-4667-3p	CLIP-seq
MIRT1057785	hsa-miR-4697-5p	CLIP-seq
MIRT1057786	hsa-miR-4718	CLIP-seq
MIRT1057787	hsa-miR-4720-5p	CLIP-seq
MIRT1057788	hsa-miR-4736	CLIP-seq
MIRT1057789	hsa-miR-4763-3p	CLIP-seq
MIRT1057790	hsa-miR-4799-3p	CLIP-seq
MIRT1057791	hsa-miR-516a-3p	CLIP-seq
MIRT1057792	hsa-miR-637	CLIP-seq
MIRT1057771	hsa-miR-1343	CLIP-seq
MIRT2013290	hsa-miR-145	CLIP-seq
MIRT2013291	hsa-miR-1913	CLIP-seq
MIRT2013292	hsa-miR-2355-3p	CLIP-seq
MIRT2013293	hsa-miR-324-3p	CLIP-seq
MIRT1057777	hsa-miR-378g	CLIP-seq
MIRT2013294	hsa-miR-3925-3p	CLIP-seq
MIRT1057779	hsa-miR-4290	CLIP-seq
MIRT1057782	hsa-miR-4488	CLIP-seq
MIRT2013295	hsa-miR-4646-3p	CLIP-seq
MIRT1057784	hsa-miR-4667-3p	CLIP-seq
MIRT1057785	hsa-miR-4697-5p	CLIP-seq
MIRT2013296	hsa-miR-508-5p	CLIP-seq
MIRT1057791	hsa-miR-516a-3p	CLIP-seq
MIRT1057792	hsa-miR-637	CLIP-seq
MIRT2245545	hsa-miR-1182	CLIP-seq
MIRT1057771	hsa-miR-1343	CLIP-seq
MIRT1057777	hsa-miR-378g	CLIP-seq
MIRT1057779	hsa-miR-4290	CLIP-seq
MIRT1057782	hsa-miR-4488	CLIP-seq
MIRT1057784	hsa-miR-4667-3p	CLIP-seq
MIRT1057785	hsa-miR-4697-5p	CLIP-seq
MIRT1057791	hsa-miR-516a-3p	CLIP-seq
MIRT1057792	hsa-miR-637	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	ISS	21740893
GO:0000302	Process	Response to reactive oxygen species	IDA	20554532
GO:0001618	Function	Virus receptor activity	IDA	11296287, 16191204
GO:0001618	Function	Virus receptor activity	IEA
GO:0001822	Process	Kidney development	ISS
GO:0002244	Process	Hematopoietic progenitor cell differentiation	IEA
GO:0003713	Function	Transcription coactivator activity	IEA
GO:0004415	Function	Hyalurononglucosaminidase activity	IDA	11296287
GO:0004415	Function	Hyalurononglucosaminidase activity	IDA	9712871, 11944887, 16600643, 17170110, 18390475, 19443707, 20554532
GO:0004415	Function	Hyalurononglucosaminidase activity	TAS
GO:0005515	Function	Protein binding	IPI	12676986, 16191204, 25416956, 32296183, 32814053, 33961781
GO:0005540	Function	Hyaluronic acid binding	IDA	12676986, 19443707
GO:0005737	Component	Cytoplasm	IDA	17170110
GO:0005764	Component	Lysosome	IDA	9712871, 16600643
GO:0005783	Component	Endoplasmic reticulum	NAS	16191204
GO:0005829	Component	Cytosol	IDA	19366691
GO:0005886	Component	Plasma membrane	IDA	18390475, 21740893
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0005902	Component	Microvillus	IDA	19366691
GO:0005975	Process	Carbohydrate metabolic process	IEA
GO:0006027	Process	Glycosaminoglycan catabolic process	IDA	9712871
GO:0009615	Process	Response to virus	IDA	11296287, 12676986
GO:0009615	Process	Response to virus	IEA
GO:0009897	Component	External side of plasma membrane	IDA	19443707
GO:0009897	Component	External side of plasma membrane	IDA	11296287, 16191204, 20554532
GO:0009897	Component	External side of plasma membrane	IEA
GO:0009986	Component	Cell surface	IDA	17170110
GO:0009986	Component	Cell surface	IEA
GO:0009986	Component	Cell surface	ISS
GO:0010764	Process	Negative regulation of fibroblast migration	IDA	19577615
GO:0016020	Component	Membrane	IEA
GO:0016324	Component	Apical plasma membrane	IDA	20554532
GO:0016787	Function	Hydrolase activity	IEA
GO:0016798	Function	Hydrolase activity, acting on glycosyl bonds	IEA
GO:0019899	Function	Enzyme binding	IEA
GO:0019899	Function	Enzyme binding	IPI	19366691
GO:0030139	Component	Endocytic vesicle	IDA	19366691
GO:0030214	Process	Hyaluronan catabolic process	IBA
GO:0030214	Process	Hyaluronan catabolic process	IDA	17170110, 19443707, 20554532, 21699545
GO:0030214	Process	Hyaluronan catabolic process	IEA
GO:0030214	Process	Hyaluronan catabolic process	TAS
GO:0030294	Function	Receptor signaling protein tyrosine kinase inhibitor activity	IDA	12676986
GO:0030308	Process	Negative regulation of cell growth	IDA	18725949
GO:0030971	Function	Receptor tyrosine kinase binding	IPI	12676986
GO:0031410	Component	Cytoplasmic vesicle	IBA
GO:0031410	Component	Cytoplasmic vesicle	IDA	16600643, 18390475
GO:0032755	Process	Positive regulation of interleukin-6 production	IDA	19443707
GO:0032757	Process	Positive regulation of interleukin-8 production	IDA	19443707
GO:0033906	Function	Hyaluronoglucuronidase activity	IBA
GO:0033906	Function	Hyaluronoglucuronidase activity	IDA	21699545
GO:0035810	Process	Positive regulation of urine volume	ISS
GO:0042117	Process	Monocyte activation	IDA	19443707
GO:0042307	Process	Positive regulation of protein import into nucleus	IEA
GO:0042307	Process	Positive regulation of protein import into nucleus	ISS
GO:0044344	Process	Cellular response to fibroblast growth factor stimulus	IDA	19577615
GO:0045121	Component	Membrane raft	IDA	21740893
GO:0045121	Component	Membrane raft	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	ISS
GO:0046677	Process	Response to antibiotic	IEP	11944887
GO:0046718	Process	Symbiont entry into host cell	ISS
GO:0048471	Component	Perinuclear region of cytoplasm	IDA	16600643
GO:0048705	Process	Skeletal system morphogenesis	IEA
GO:0050431	Function	Transforming growth factor beta binding	IEA
GO:0050431	Function	Transforming growth factor beta binding	ISS
GO:0050729	Process	Positive regulation of inflammatory response	IDA	19443707
GO:0051216	Process	Cartilage development	IEP	11944887
GO:0051607	Process	Defense response to virus	IEA
GO:0051898	Process	Negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA	12676986
GO:0060586	Process	Multicellular organismal-level iron ion homeostasis	IEA
GO:0070295	Process	Renal water absorption	ISS
GO:0071347	Process	Cellular response to interleukin-1	IDA	18390475
GO:0071356	Process	Cellular response to tumor necrosis factor	IEP	18390475
GO:0071493	Process	Cellular response to UV-B	IDA	21699545
GO:0071560	Process	Cellular response to transforming growth factor beta stimulus	IDA	19366691
GO:0071560	Process	Cellular response to transforming growth factor beta stimulus	IEA
GO:0090575	Component	RNA polymerase II transcription regulator complex	IEA
GO:0090575	Component	RNA polymerase II transcription regulator complex	ISS	19366691
GO:0098552	Component	Side of membrane	IEA
GO:2001238	Process	Positive regulation of extrinsic apoptotic signaling pathway	IEA
GO:2001238	Process	Positive regulation of extrinsic apoptotic signaling pathway	ISS	19366691

Other IDs

• MIM: 603551
• HGNC: 5321
• e!Ensembl: ENSG00000068001

Protein

• UniProt ID: Q12891
• Protein name: Hyaluronidase-2 (Hyal-2) (EC 3.2.1.35) (Hyaluronoglucosaminidase-2) (Lung carcinoma protein 2) (LuCa-2)
• Protein function: Catalyzes hyaluronan degradation into small fragments that are endocytosed and degraded in lysosomes by HYAL1 and exoglycosidases (PubMed:9712871). Essential for the breakdown of extracellular matrix hyaluronan (PubMed:28081210). {ECO:0000269|Pu
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01630	Glyco_hydro_56	29 → 362	Hyaluronidase	Domain

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed (at protein level). {ECO:0000269|PubMed:9712871}.
• Sequence:

  MRAGPGPTVTLALVLAVSWAMELKPTAPPIFTGRPFVVAWDVPTQDCGPRLKVPLDLNAF
  DVQASPNEGFVNQNITIFYRDRLGLYPRFDSAGRSVHGGVPQNVSLWAHRKMLQKRVEHY
  IRTQESAGLAVIDWEDWRPVWVRNWQDKDVYRRLSRQLVASRHPDWPPDRIVKQAQYEFE
  FAAQQFMLETLRYVKAVRPRHLWGFYLFPDCYNHDYVQNWESYTGRCPDVEVARNDQLAW
  LWAESTALFPSVYLDETLASSRHGRNFVSFRVQEALRVARTHHANHALPVYVFTRPTYSR
  RLTGLSEMDLISTIGESAALGAAGVILWGDAGYTTSTETCQYLKDYLTRLLVPYVVNVSW
  ATQYCSRAQCHGHGRCVRRNPSASTFLHLSTNSFRLVPGHAPGEPQLRPVGELSWADIDH
  LQTHFRCQCYLGWSGEQCQWDHRQAAGGASEAWAGSHLTSLLALAALAFTWTL

• Sequence length: 473

Pathways

KEGG:

Glycosaminoglycan degradation
Metabolic pathways
Lysosome

Reactome:

Hyaluronan uptake and degradation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
HYAL2 deficiency	Pathogenic; Likely pathogenic	rs139960719, rs2109322411, rs1553715895, rs782682203, rs781999115, rs2109324483, rs2109324707, rs1321268291, rs1553716439, rs782642246	RCV001731165 RCV001731164 RCV001731163 RCV001731162 RCV001731160 RCV001731159 RCV001731158 RCV001731157 RCV001731156 RCV001731155	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Muggenthaler-Chowdhury-Chioza syndrome	Pathogenic; Likely pathogenic	rs2109322411, rs1553715895, rs782682203, rs781999115, rs2109324483, rs1321268291, rs1553716439, rs782642246	RCV005002012 RCV005002011 RCV005002010 RCV005002008 RCV005002007 RCV005002006 RCV005002005 RCV005002004	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CLEFT LIP AND PALATE, CRANIOFACIAL DYSMORPHISM, CONGENITAL HEART DEFECT, HEARING LOSS SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CLEFT LIP AND PALATE-CRANIOFACIAL DYSMORPHISM-CONGENITAL HEART DEFECT-HEARING LOSS SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GASTROESOPHAGEAL REFLUX DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYAL2-related disorder	Conflicting classifications of pathogenicity; Uncertain significance; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OROFACIAL CLEFT	—	Disgenet, GenCC Disgenet, GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PEPTIC ULCER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma	Adenocarcinoma	BEFREE	12596899		★☆☆☆☆ Found in Text Mining only
ANOPHTHALMIA AND PULMONARY HYPOPLASIA	Syndromic microphthalmia	BEFREE	28978057		★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	BEFREE	15535829		★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	Pubtator	15535829	Associate	★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	15535829	Associate	★☆☆☆☆ Found in Text Mining only
B-Cell Lymphomas	B-Cell Lymphoma	BEFREE	15386412		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	12584308, 16125700, 20473947, 25213452		★☆☆☆☆ Found in Text Mining only
Bronchioloalveolar Adenocarcinoma	Lung adenocarcinoma	BEFREE	11296287, 12676986		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	11296287	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	BEFREE	23202930		★☆☆☆☆ Found in Text Mining only
Carcinoma Endometrioid	Endometrioid carcinoma	Pubtator	20875124	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	12596899, 12676986, 17255269		★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular disease	Pubtator	39285429	Associate	★☆☆☆☆ Found in Text Mining only
Cleft lip and palate-craniofacial dysmorphism-congenital heart defect-hearing loss syndrome	Cleft Lip And Palate-Craniofacial Dysmorphism-Congenital Heart Defect-Hearing Loss Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colitis	Colitis	BEFREE	31262781		★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	26453961		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	30972813		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	20849597, 26453961	Associate	★☆☆☆☆ Found in Text Mining only
Congenital Heart Defects	Congenital heart defects	BEFREE	28196902		★☆☆☆☆ Found in Text Mining only
Coronary Disease	Coronary artery disease	Pubtator	39285429	Associate	★☆☆☆☆ Found in Text Mining only
Cutaneous Melanoma	Melanoma	BEFREE	23560496		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	15535829, 28765635		★☆☆☆☆ Found in Text Mining only
Depressive Disorder Major	Major depressive disorder	Pubtator	36281744	Associate	★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down syndrome	Pubtator	15890266	Associate	★☆☆☆☆ Found in Text Mining only
Endometrial Carcinoma	Endometrial carcinoma	BEFREE	15936804		★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	20875124	Inhibit	★☆☆☆☆ Found in Text Mining only
Endometriosis	Endometriosis	BEFREE	29621955		★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	36290884	Associate	★☆☆☆☆ Found in Text Mining only
Familial Primary Pulmonary Hypertension	Pulmonary hypertension	Pubtator	18776053	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	LHGDN	12684632		★☆☆☆☆ Found in Text Mining only
Graves Ophthalmopathy	Graves ophthalmopathy	Pubtator	32084270	Associate	★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	32583022	Associate	★☆☆☆☆ Found in Text Mining only
High Grade Lymphoma (neoplasm)	High Grade Lymphoma	BEFREE	15386412		★☆☆☆☆ Found in Text Mining only
Hyaluronidase Deficiency	Hyaluronidase Deficiency	BEFREE	10339581		★☆☆☆☆ Found in Text Mining only
Idiopathic pulmonary hypertension	Pulmonary Hypertension	BEFREE	18776053		★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory Bowel Disease	BEFREE	31262781		★☆☆☆☆ Found in Text Mining only
Intervertebral Disc Degeneration	Intervertebral disc disease	Pubtator	33251629	Associate	★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	11296287	Inhibit	★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung Neoplasms	BEFREE	17255269		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung Neoplasms	LHGDN	19140316		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	19181417	Associate	★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	BEFREE	15386412		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	12584308, 16125700, 20473947, 25213452		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	12596899, 12676986, 17255269		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	15936804, 20849597, 28978057, 31752354		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	26453961		★☆☆☆☆ Found in Text Mining only
Melanoma Cutaneous Malignant	Melanoma	Pubtator	23560496	Associate	★☆☆☆☆ Found in Text Mining only
Mesothelioma Malignant	Mesothelioma	Pubtator	37334363	Associate	★☆☆☆☆ Found in Text Mining only
Nasal Polyps	Nasal polyp	Pubtator	23377816	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	11296287, 11836391, 12584308, 12676986, 15386412, 15936804, 17255269, 18725949, 27845895, 31080060		★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	15535829	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	19435493, 23202930, 35767191	Associate	★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	15681498	Associate	★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	34354097	Stimulate	★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	15535829		★☆☆☆☆ Found in Text Mining only
Small cell carcinoma of lung	Lung carcinoma	LHGDN	12684632		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	BEFREE	18725949		★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	22430805	Associate	★☆☆☆☆ Found in Text Mining only
Stable angina	Stable Angina	BEFREE	30236312		★☆☆☆☆ Found in Text Mining only
Stroke	Stroke	Pubtator	39285429	Associate	★☆☆☆☆ Found in Text Mining only
Submucous cleft of hard palate	Submucosal cleft palate	BEFREE	28081210		★☆☆☆☆ Found in Text Mining only
Submucous cleft palate	Submucosal cleft palate	BEFREE	28081210		★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple Negative Breast Neoplasms	BEFREE	26112095, 31080060		★☆☆☆☆ Found in Text Mining only