HYAL1

hyaluronidase 1, the group of Hyaluronidases

Basic information

Region (hg38): 3:50299890-50312381

Links

ENSG00000114378 ∙ NCBI:3373 ∙ OMIM:607071 ∙ HGNC:5320 ∙ Uniprot:Q12794 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mucopolysaccharidosis type 9 (Definitive), mode of inheritance: AR
• mucopolysaccharidosis type 9 (Strong), mode of inheritance: AR
• mucopolysaccharidosis type 9 (Limited), mode of inheritance: AR
• mucopolysaccharidosis type 9 (Supportive), mode of inheritance: AR
• mucopolysaccharidosis type 9 (Strong), mode of inheritance: AR
• mucopolysaccharidosis type 9 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mucopolysaccharidosis type IX	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Craniofacial; Dermatologic; Musculoskeletal	8793927; 10339581

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HYAL1 gene.

• Deficiency of hyaluronoglucosaminidase (33 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HYAL1 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			1	154		155
missense			86	4	4	94
nonsense	15		1			16
start loss			1			1
frameshift	18	1	2			21
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region				6		6
non coding			8	23	3	34
Total	33	2	100	181	7

Highest pathogenic variant AF is 0.0000131

Variants in HYAL1

This is a list of pathogenic ClinVar variants found in the HYAL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-50299991-G-A		Deficiency of hyaluronoglucosaminidase	Benign (Jan 12, 2018)
3-50300024-C-T		Deficiency of hyaluronoglucosaminidase	Uncertain significance (Jan 12, 2018)
3-50300049-G-A		Deficiency of hyaluronoglucosaminidase	Uncertain significance (Jan 13, 2018)
3-50300150-G-C		Deficiency of hyaluronoglucosaminidase	Uncertain significance (Jan 13, 2018)
3-50300262-A-G		Deficiency of hyaluronoglucosaminidase	Benign/Likely benign (Feb 01, 2020)
3-50300310-A-G		Deficiency of hyaluronoglucosaminidase	Uncertain significance (Jan 13, 2018)
3-50300377-C-G		Deficiency of hyaluronoglucosaminidase	Uncertain significance (Jan 13, 2018)
3-50300492-G-A		Deficiency of hyaluronoglucosaminidase	Likely benign (Apr 18, 2023)
3-50300493-C-T		not specified	Uncertain significance (May 24, 2023)
3-50300499-C-T		Deficiency of hyaluronoglucosaminidase • not specified	Conflicting classifications of pathogenicity (Mar 24, 2023)
3-50300500-G-A		Deficiency of hyaluronoglucosaminidase	Uncertain significance (Aug 09, 2022)
3-50300501-C-G		Deficiency of hyaluronoglucosaminidase • not specified	Uncertain significance (Oct 25, 2022)
3-50300503-C-T		not specified	Uncertain significance (Aug 04, 2023)
3-50300510-C-T		Deficiency of hyaluronoglucosaminidase	Likely benign (Nov 06, 2023)
3-50300511-G-A		Deficiency of hyaluronoglucosaminidase	Uncertain significance (Feb 01, 2021)
3-50300514-G-C		Deficiency of hyaluronoglucosaminidase	Benign (Jan 31, 2024)
3-50300522-G-T		Deficiency of hyaluronoglucosaminidase	Likely benign (Oct 07, 2022)
3-50300524-C-T		Deficiency of hyaluronoglucosaminidase	Uncertain significance (Oct 24, 2022)
3-50300526-G-C		not specified	Likely benign (Jan 31, 2024)
3-50300527-G-T		Deficiency of hyaluronoglucosaminidase	Uncertain significance (Aug 30, 2021)
3-50300535-C-T		Deficiency of hyaluronoglucosaminidase	Uncertain significance (Jul 19, 2022)
3-50300546-C-T		Deficiency of hyaluronoglucosaminidase	Likely benign (Sep 08, 2023)
3-50300560-G-A		Deficiency of hyaluronoglucosaminidase	Uncertain significance (Aug 03, 2022)
3-50300561-T-A		Deficiency of hyaluronoglucosaminidase	Likely benign (Dec 14, 2023)
3-50300561-T-C		Deficiency of hyaluronoglucosaminidase	Likely benign (Nov 24, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HYAL1	protein_coding	protein_coding	ENST00000266031	3	12493

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000191	0.907	125711	0	37	125748	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.315	252	266	0.946	0.0000173	2812
Missense in Polyphen		93	98.118	0.94784		1105
Synonymous	0.00526	108	108	0.999	0.00000642	926
Loss of Function	1.52	8	14.2	0.564	6.25e-7	144

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000330	0.000329
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000151	0.000149
Middle Eastern	0.000218	0.000217
South Asian	0.000263	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May have a role in promoting tumor progression. May block the TGFB1-enhanced cell growth. {ECO:0000269|PubMed:12084718}.
• Pathway: Lysosome - Homo sapiens (human);Glycosaminoglycan degradation - Homo sapiens (human);Metabolism of carbohydrates;CS/DS degradation;Chondroitin sulfate/dermatan sulfate metabolism;Glycosaminoglycan metabolism;chondroitin sulfate degradation (metazoa);Metabolism;dermatan sulfate degradation (metazoa) (Consensus)

Intolerance Scores

• loftool: 0.716
• rvis_EVS: 0.11
• rvis_percentile_EVS: 62

Haploinsufficiency Scores

• pHI: 0.108
• hipred: N
• hipred_score: 0.146
• ghis: 0.468

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0278

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hyal1
• Phenotype: skeleton phenotype; immune system phenotype; respiratory system phenotype; liver/biliary system phenotype

Gene ontology

• Biological process: response to reactive oxygen species;carbohydrate metabolic process;inflammatory response;response to virus;positive regulation of epithelial cell migration;chondroitin sulfate catabolic process;hyaluronan metabolic process;hyaluronan biosynthetic process;hyaluronan catabolic process;positive regulation of cell growth;negative regulation of cell growth;cellular response to platelet-derived growth factor stimulus;cellular response to fibroblast growth factor stimulus;positive regulation of angiogenesis;positive regulation of cell adhesion;positive regulation of growth;response to antibiotic;viral entry into host cell;positive regulation of epithelial cell proliferation;cartilage development;embryonic skeletal joint morphogenesis;cellular response to interleukin-1;cellular response to tumor necrosis factor;cellular response to pH;cellular response to UV-B;positive regulation of G1/S transition of mitotic cell cycle;positive regulation of hyaluranon cable assembly
• Cellular component: extracellular space;cytoplasm;lysosome;cytoplasmic vesicle;hyaluranon cable;lysosomal lumen;extracellular exosome
• Molecular function: virus receptor activity;hyalurononglucosaminidase activity;transcription factor binding;hyaluronan synthase activity