HYAL4

protein-coding

hyaluronidase 4, the group of Hyaluronidases

Gene summary

This gene encodes a protein which is similar in structure to hyaluronidases but lacks hyaluronidase activity. The encoded protein acts as a chondroitin-sulfate-specific endo-beta-N-acetylgalactosaminidase; that is, it exhibits hydrolytic activity toward chondroitin sulfate chains and degrades them into oligosaccharides. Proteoglycans are formed by the covalent linkage of chondroitin sulfate chains to protein. Proteoglycans are ubiquitous components of the extracellular matrix of connective tissues and are also found at the surface of many cell types where they participate in a variety of cellular processes such as cell proliferation, differentiation, migration, cell-cell recognition, extracellular matrix deposition, and tissue morphogenesis. The expression of this gene is highest in testes and placenta. [provided by RefSeq, Apr 2019]

MANE transcript

NM_012269.3

Inheritance

—

ClinVar variants

U:68B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.21

Max pathogenic AF

—

Genomic locus

chr7:123,828,983-123,877,481

External References & Databases

Ensembl (ENSG00000106302)

Transcript & Mutation Effects

hg38 • Region Span ~48.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HYAL4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012269.3. 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 clinvar	1 clinvar		2
missense			67 clinvar	1 clinvar		68
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	68	2	0	70

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012269.3	RefSeq	NP_036401.2	3	MANE Select
ENST00000223026.9	Ensembl	ENSP00000223026.4	3	MANE Select
ENST00000476325.5	Ensembl	ENSP00000417186.1	3	Standard
ENST00000476325.6	Ensembl	ENSP00000417186.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glycosaminoglycan degradation - Homo sapiens (human)
chondroitin sulfate degradation (metazoa)

Biological Process

carbohydrate metabolic process
glycosaminoglycan catabolic process
chondroitin sulfate catabolic process

Molecular Function

hyalurononglucosaminidase activity

Cellular Component

cell surface
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000223026
Coding exons: 3
Length: 48496
Individuals with no LoFs: 125409
Homozygous LoFs: 0
Heterozygous LoFs: 337
Defined: 125746
p: 0.00134

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0993	258	254	1.02	0.0000121	3134
Missense (PolyPhen)		89	89.052	0.99941		1170
Synonymous	1.23	79	94.2	0.839	0.00000494	923
Loss of Function	-0.831	23	19.1	1.21	0.00000104	228

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0013	0.0013	notable
Latino/Admixed American	0.00051	0.00049	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0012	0.0012	notable
Finnish	0.0012	0.0012	notable
European (Non-Finnish)	0.0019	0.0019	notable
South Asian	0.00080	0.00075	rare
Other	0.0017	0.0016	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Endo-hyaluronidase that degrades hyaluronan to smaller oligosaccharide fragments. Has also chondroitin sulfate hydrolase activity, The best substrate being the galactosaminidic linkage in the sequence of a trisulfated tetrasaccharide. {ECO:0000269|PubMed:16104017, ECO:0000269|PubMed:19889881}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.929
RVIS EVS: 0.73
RVIS percentile EVS: 86.21

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.115

Gene Damage Prediction

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