Mucopolysaccharidosis type 9

Summary

Mucopolysaccharidosis type 9 (MONDO:0011093) is a disease caused by HYAL1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Europe)
• Causal gene: HYAL1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 401
• Phenotypes (HPO): 2

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

2 HPO clinical features (Orphanet curated; top 2 by frequency):

HPO ID	Term	Frequency
HP:0003170	Abnormality of the acetabulum	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	mucopolysaccharidosis type 9
Mondo ID	MONDO:0011093
MeSH	C563209
OMIM	601492
Orphanet	67041
DOID	DOID:0050809
ICD-11	952591271
NCIT	C129073
SNOMED CT	124473006
UMLS	C1291490
MedGen	226942
GARD	0016675
Is cancer (heuristic)	no

Also known as: MPS9 · MPSIX · mucopolysaccharidosis type 9 · mucopolysaccharidosis type IX · mucopolysaccharidosis, type IX

Data availability: 401 ClinVar variants · 6 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › mucopolysaccharidosis type 9

Related subtypes (26): bone remodeling disease, disease of bone structure, mucopolysaccharidosis type 1, bone inflammation disease, Baastrup syndrome, periostitis, osteonecrosis, bone development disease, ainhum, cervical rib disease, coxoauricular syndrome, metachondromatosis, Sagliker syndrome, mixed sclerosing bone dystrophy with extra-skeletal manifestations, GM1 gangliosidosis, skeletal dysplasia, autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome, mucopolysaccharidosis type 3, bone neoplasm, skull disorder, Duane anomaly-myopathy-scoliosis syndrome, mueller-weiss syndrome, SLC10A7-congenital disorder of glycosylation, metabolic bone disorder, proteoglycan-related bone disorder, ACAN-related short stature spectrum

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

401 retrieved; paginated sample, class counts are floors:

191 likely benign, 127 uncertain significance, 29 pathogenic, 15 likely pathogenic, 13 conflicting classifications of pathogenicity, 12 pathogenic/likely pathogenic, 11 benign, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069022	NM_033159.4(HYAL1):c.238_239del (p.Gly80fs)	HYAL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070786	NM_033159.4(HYAL1):c.586_598del (p.Arg196fs)	HYAL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072055	NM_033159.4(HYAL1):c.707G>A (p.Trp236Ter)	HYAL1	Pathogenic	criteria provided, single submitter
1073037	NM_033159.4(HYAL1):c.787C>T (p.Gln263Ter)	HYAL1	Pathogenic	criteria provided, single submitter
1074510	NM_033159.4(HYAL1):c.691del (p.Gln231fs)	HYAL1	Pathogenic	criteria provided, single submitter
1342863	NM_033159.4(HYAL1):c.104del (p.Val35fs)	HYAL1	Pathogenic	criteria provided, multiple submitters, no conflicts
1365687	NM_033159.4(HYAL1):c.521_524dup (p.Phe175fs)	HYAL1	Pathogenic	criteria provided, single submitter
1396264	NM_033159.4(HYAL1):c.221dup (p.Tyr75fs)	HYAL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1402860	NM_033159.4(HYAL1):c.663_670dup (p.Gly224fs)	HYAL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1447779	NM_033159.4(HYAL1):c.546G>A (p.Trp182Ter)	HYAL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1452834	NM_033159.4(HYAL1):c.937C>T (p.Gln313Ter)	HYAL1	Pathogenic	criteria provided, single submitter
1454959	NM_033159.4(HYAL1):c.81del (p.Asn29fs)	HYAL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455812	NM_033159.4(HYAL1):c.445C>T (p.Gln149Ter)	HYAL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458685	NC_000003.11:g.(?50338409)(50341042_?)del	HYAL1	Pathogenic	criteria provided, single submitter
1988949	NM_033159.4(HYAL1):c.221del (p.Phe74fs)	HYAL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2018303	NM_033159.4(HYAL1):c.410G>A (p.Trp137Ter)	HYAL1	Pathogenic	criteria provided, single submitter
2023599	NM_033159.4(HYAL1):c.597G>A (p.Trp199Ter)	HYAL1	Pathogenic	criteria provided, single submitter
2052431	NM_033159.4(HYAL1):c.4del (p.Ala2fs)	HYAL1	Pathogenic	criteria provided, single submitter
2062762	NM_033159.4(HYAL1):c.345_348dup (p.Ile117fs)	HYAL1	Pathogenic	criteria provided, single submitter
2115682	NM_033159.4(HYAL1):c.440del (p.Tyr147fs)	HYAL1	Pathogenic	criteria provided, single submitter
2173294	NM_033159.4(HYAL1):c.110_134dup (p.Arg46fs)	HYAL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2199188	NM_033159.4(HYAL1):c.390G>A (p.Trp130Ter)	HYAL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2427429	NC_000003.11:g.(?50340112)(50342638_?)del	HYAL1	Pathogenic	criteria provided, single submitter
2695909	NM_033159.4(HYAL1):c.250del (p.Tyr84fs)	HYAL1	Pathogenic	criteria provided, single submitter
2743470	NM_033159.4(HYAL1):c.201del (p.Gly68fs)	HYAL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2745132	NM_033159.4(HYAL1):c.268del (p.Glu90fs)	HYAL1	Pathogenic	criteria provided, single submitter
2780854	NM_033159.4(HYAL1):c.658C>T (p.Gln220Ter)	HYAL1	Pathogenic	criteria provided, single submitter
2817930	NM_033159.4(HYAL1):c.545G>A (p.Trp182Ter)	HYAL1	Pathogenic	criteria provided, single submitter
2849597	NM_033159.4(HYAL1):c.599del (p.Gly200fs)	HYAL1	Pathogenic	criteria provided, single submitter
2849832	NM_033159.4(HYAL1):c.190C>T (p.Gln64Ter)	HYAL1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
HYAL1	Definitive	Autosomal recessive	mucopolysaccharidosis type 9	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HYAL1	Orphanet:67041	Hyaluronidase deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HYAL1	HGNC:5320	ENSG00000114378	Q12794	Hyaluronidase-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HYAL1	Hyaluronidase-1	May have a role in promoting tumor progression.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HYAL1	Enzyme (other)	yes	3.2.1.35	Aldolase_TIM, GH_hydrolase_sf, Hyaluronidase

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	1
right lobe of liver	1
spleen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HYAL1	142	broad	marker	right lobe of liver, liver, spleen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HYAL1	1,953

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HYAL1	Q12794	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MPS IX - Natowicz syndrome (Hyaluronan metabolism)	1	11420.0×	2e-04	HYAL1
MPS IX - Natowicz syndrome (CS/DS degradation)	1	11420.0×	2e-04	HYAL1
Hyaluronan degradation	1	713.8×	0.002	HYAL1
CS/DS degradation	1	543.8×	0.002	HYAL1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of hyaluranon cable assembly	1	5617.3×	0.002	HYAL1
chondroitin sulfate proteoglycan catabolic process	1	2808.7×	0.002	HYAL1
hyaluronan metabolic process	1	2106.5×	0.002	HYAL1
cellular response to pH	1	2106.5×	0.002	HYAL1
embryonic skeletal joint morphogenesis	1	1532.0×	0.002	HYAL1
cellular response to UV-B	1	1404.3×	0.002	HYAL1
response to reactive oxygen species	1	1053.2×	0.003	HYAL1
hyaluronan catabolic process	1	991.3×	0.003	HYAL1
response to antibiotic	1	702.2×	0.003	HYAL1
cellular response to platelet-derived growth factor stimulus	1	648.1×	0.003	HYAL1
cellular response to fibroblast growth factor stimulus	1	543.6×	0.004	HYAL1
cellular response to interleukin-1	1	280.9×	0.006	HYAL1
positive regulation of cell adhesion	1	271.8×	0.006	HYAL1
cartilage development	1	251.5×	0.006	HYAL1
positive regulation of cell growth	1	183.2×	0.008	HYAL1
cellular response to tumor necrosis factor	1	163.6×	0.008	HYAL1
response to virus	1	144.0×	0.008	HYAL1
negative regulation of cell growth	1	144.0×	0.008	HYAL1
carbohydrate metabolic process	1	135.9×	0.008	HYAL1
positive regulation of angiogenesis	1	115.4×	0.009	HYAL1
inflammatory response	1	37.7×	0.027	HYAL1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HYAL1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
HYAL1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HYAL1	3.2.1.35, 4.2.2.1	hyaluronoglucosaminidase, hyaluronate lyase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	HYAL1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
HYAL1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.