Urofacial syndrome type 1

Summary

Urofacial syndrome type 1 (MONDO:0009368) is a disease caused by HPSE2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: HPSE2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 106

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	urofacial syndrome type 1
Mondo ID	MONDO:0009368
OMIM	236730
GARD	0024666
Is cancer (heuristic)	no

Also known as: UFS1 · urofacial syndrome 1 · urofacial syndrome type 1

Data availability: 106 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › Ochoa syndrome › urofacial syndrome type 1

Related subtypes (1): urofacial syndrome 2

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

106 retrieved; paginated sample, class counts are floors:

74 uncertain significance, 9 pathogenic, 7 benign/likely benign, 7 likely pathogenic, 3 benign, 3 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323070	NM_021828.5(HPSE2):c.902T>A (p.Leu301Ter)	HPSE2	Pathogenic	criteria provided, single submitter
1691124	NM_021828.5(HPSE2):c.429T>A (p.Tyr143Ter)	HPSE2	Pathogenic	criteria provided, single submitter
1691127	NM_021828.5(HPSE2):c.1099-1G>A	HPSE2	Pathogenic	criteria provided, multiple submitters, no conflicts
60719	NM_021828.5(HPSE2):c.1628A>T (p.Asn543Ile)	HPSE2	Pathogenic	no assertion criteria provided
83	NM_021828.5(HPSE2):c.1516C>T (p.Arg506Ter)	HPSE2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
84	NM_021828.5(HPSE2):c.1465_1466del (p.Asn489fs)	HPSE2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
85	NM_021828.5(HPSE2):c.241_242del (p.Leu81fs)	HPSE2	Pathogenic	no assertion criteria provided
86	NM_021828.5:c.1099-4166_1320+840delins23	HPSE2	Pathogenic	no assertion criteria provided
87	NG_023416.2:g.(88604_176551)_(176714_576894)del	HPSE2	Pathogenic	no assertion criteria provided
88	NM_021828.5(HPSE2):c.1414C>T (p.Arg472Ter)	HPSE2	Pathogenic	criteria provided, single submitter
89	NM_021828.5(HPSE2):c.457C>T (p.Arg153Ter)	HPSE2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
90	NM_021828.5(HPSE2):c.57dup (p.Ala20fs)	HPSE2	Pathogenic	criteria provided, multiple submitters, no conflicts
3589444	NM_021828.5(HPSE2):c.1407del (p.Pro470fs)	HPSE2	Likely pathogenic	criteria provided, single submitter
3589471	NM_021828.5(HPSE2):c.1308del (p.Phe436fs)	HPSE2	Likely pathogenic	criteria provided, single submitter
3589544	NM_021828.5(HPSE2):c.1145_1149del (p.Val382fs)	HPSE2	Likely pathogenic	criteria provided, single submitter
3589552	NM_021828.5(HPSE2):c.1113del (p.Thr370_Tyr371insTer)	HPSE2	Likely pathogenic	criteria provided, single submitter
3589700	NM_021828.5(HPSE2):c.291-1G>T	HPSE2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3589704	NM_021828.5(HPSE2):c.250del (p.Asp84fs)	HPSE2	Likely pathogenic	criteria provided, single submitter
4849308	NM_021828.5(HPSE2):c.1337_1338del (p.Leu446fs)	HPSE2	Likely pathogenic	criteria provided, single submitter
3589466	NM_021828.5(HPSE2):c.1320+5G>A	HPSE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3589484	NM_021828.5(HPSE2):c.1296G>C (p.Val432=)	HPSE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030769	NM_021828.5(HPSE2):c.55C>T (p.Pro19Ser)	HPSE2	Uncertain significance	criteria provided, single submitter
1040032	NM_021828.5(HPSE2):c.1696G>A (p.Gly566Ser)	HPSE2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1372181	NM_021828.5(HPSE2):c.799C>T (p.Arg267Trp)	HPSE2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1507141	NM_021828.5(HPSE2):c.815G>A (p.Arg272Gln)	HPSE2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2186757	NM_021828.5(HPSE2):c.145G>A (p.Val49Ile)	HPSE2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2220681	NM_021828.5(HPSE2):c.1750G>A (p.Val584Ile)	HPSE2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2253798	NM_021828.5(HPSE2):c.119A>G (p.Gln40Arg)	HPSE2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2293789	NM_021828.5(HPSE2):c.211G>A (p.Val71Ile)	HPSE2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2592719	NM_021828.5(HPSE2):c.1168A>G (p.Thr390Ala)	HPSE2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
HPSE2	Definitive	Autosomal recessive	urofacial syndrome type 1	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HPSE2	Orphanet:2704	Urofacial syndrome

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
HPSE2	HGNC:18374	ENSG00000172987	Q8WWQ2	Inactive heparanase-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HPSE2	Inactive heparanase-2	Binds heparin and heparan sulfate with high affinity, but lacks heparanase activity.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HPSE2	Other/Unknown	no		Glyco_hydro_79, GH_hydrolase_sf

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
calcaneal tendon	1
lower esophagus	1
lower esophagus muscularis layer	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HPSE2	153	tissue_specific	marker	calcaneal tendon, lower esophagus muscularis layer, lower esophagus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HPSE2	541

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HPSE2	Q8WWQ2	82.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
HS-GAG degradation	1	496.5×	0.002	HPSE2

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
extracellular matrix organization	1	122.1×	0.015	HPSE2
cell population proliferation	1	102.8×	0.015	HPSE2
positive regulation of cell population proliferation	1	33.6×	0.030	HPSE2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HPSE2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	HPSE2

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)
HPSE2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.