Usher syndrome type 1G

Summary

Usher syndrome type 1G (MONDO:0011748) is a disease caused by USH1G (GenCC Definitive), with 2 cohort genes and 1 clinical trial.

At a glance

• Causal gene: USH1G (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 105
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Usher syndrome type 1G
Mondo ID	MONDO:0011748
MeSH	C564643
OMIM	606943
DOID	DOID:0110834
UMLS	C1847089
MedGen	339683
GARD	0015404
Is cancer (heuristic)	no

Also known as: USH1G · USH1G Usher syndrome · Usher syndrome caused by mutation in USH1G · Usher syndrome type 1G · USHER syndrome, type Ig

Data availability: 105 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Usher syndrome › Usher syndrome type 1 › Usher syndrome type 1G

Related subtypes (8): Usher syndrome type 1C, Usher syndrome type 1D, Usher syndrome type 1F, Usher syndrome type 1E, Usher syndrome type 1H, Usher syndrome type 1K, Usher syndrome, type 1D/F, Usher syndrome type 1B

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

105 retrieved; paginated sample, class counts are floors:

41 uncertain significance, 20 pathogenic, 14 conflicting classifications of pathogenicity, 10 likely benign, 7 likely pathogenic, 6 pathogenic/likely pathogenic, 5 benign, 1 benign/likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
287391	NM_173477.5(USH1G):c.1311del (p.Lys438fs)	LOC130061627	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4933	NM_001384140.1(PCDH15):c.733C>T (p.Arg245Ter)	PCDH15	Pathogenic	criteria provided, multiple submitters, no conflicts
1023449	NM_173477.5(USH1G):c.164+5G>A	USH1G	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1254706	NM_173477.5(USH1G):c.191G>A (p.Trp64Ter)	USH1G	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323744	NM_173477.5(USH1G):c.387dup (p.Lys130fs)	USH1G	Pathogenic	criteria provided, multiple submitters, no conflicts
1323745	NM_173477.5(USH1G):c.711del (p.Arg238fs)	USH1G	Pathogenic	criteria provided, single submitter
2445661	NM_173477.5(USH1G):c.1324del (p.Ala442fs)	USH1G	Pathogenic	criteria provided, single submitter
2445662	NM_173477.5(USH1G):c.85dup (p.Asp29fs)	USH1G	Pathogenic	criteria provided, single submitter
2736644	NM_173477.5(USH1G):c.84dup (p.Asp29fs)	USH1G	Pathogenic	criteria provided, multiple submitters, no conflicts
2741442	NM_173477.5(USH1G):c.275G>A (p.Trp92Ter)	USH1G	Pathogenic	criteria provided, multiple submitters, no conflicts
2914	NM_173477.5(USH1G):c.143T>C (p.Leu48Pro)	USH1G	Pathogenic	no assertion criteria provided
2915	NM_173477.5(USH1G):c.186_187del (p.Ile63fs)	USH1G	Pathogenic	no assertion criteria provided
2916	NM_173477.5(USH1G):c.832_851del (p.Ser278fs)	USH1G	Pathogenic	criteria provided, single submitter
2917	NM_173477.5(USH1G):c.394dup (p.Val132fs)	USH1G	Pathogenic	no assertion criteria provided
2918	NM_173477.5(USH1G):c.113G>A (p.Trp38Ter)	USH1G	Pathogenic	criteria provided, single submitter
31577	NM_173477.5(USH1G):c.163_164+13del	USH1G	Pathogenic	no assertion criteria provided
3582821	NM_173477.5(USH1G):c.723_726dup (p.Ser243fs)	USH1G	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3601022	NM_173477.5(USH1G):c.104_107dup (p.Leu37fs)	USH1G	Pathogenic	criteria provided, single submitter
3601025	NM_173477.5(USH1G):c.146_147insAG (p.Leu50fs)	USH1G	Pathogenic	criteria provided, single submitter
3601026	NM_173477.5(USH1G):c.495C>G (p.Tyr165Ter)	USH1G	Pathogenic	criteria provided, single submitter
3601027	NM_173477.5(USH1G):c.758_765dup (p.Val256Ter)	USH1G	Pathogenic	criteria provided, single submitter
3601028	NM_173477.5(USH1G):c.801G>A (p.Trp267Ter)	USH1G	Pathogenic	criteria provided, single submitter
48127	NM_173477.5(USH1G):c.1373A>T (p.Asp458Val)	USH1G	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
560918	NM_173477.5(USH1G):c.511G>T (p.Glu171Ter)	USH1G	Pathogenic	criteria provided, single submitter
627491	NM_173477.5(USH1G):c.1060G>T (p.Asp354Tyr)	USH1G	Pathogenic	no assertion criteria provided
856259	NM_173477.5(USH1G):c.1004dup (p.Leu336fs)	USH1G	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3582819	NM_173477.5(USH1G):c.1150_1156del (p.Asp384fs)	USH1G	Likely pathogenic	criteria provided, single submitter
3582820	NM_173477.5(USH1G):c.742del (p.Gln248fs)	USH1G	Likely pathogenic	criteria provided, single submitter
3582822	NM_173477.5(USH1G):c.623dup (p.Thr209fs)	USH1G	Likely pathogenic	criteria provided, single submitter
3582824	NM_173477.5(USH1G):c.445G>T (p.Glu149Ter)	USH1G	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 3 · 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
USH1G	Definitive	Unknown	Usher syndrome type 1	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
USH1G	Orphanet:231169	Usher syndrome type 1
PCDH15	Orphanet:231169	Usher syndrome type 1
PCDH15	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
USH1G	HGNC:16356	ENSG00000182040	Q495M9	pre-mRNA splicing regulator USH1G	gencc,clinvar
PCDH15	HGNC:14674	ENSG00000150275	Q96QU1	Protocadherin-15	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
USH1G	pre-mRNA splicing regulator USH1G	Plays a role in pre-mRNA splicing by regulating the release and transfer of U4/U6.U5 tri-small nuclear ribonucleoprotein (tri-snRNP) complexes from their assembly site in Cajal bodies to nuclear speckles, thereby contributing to the assemb…
PCDH15	Protocadherin-15	Calcium-dependent cell-adhesion protein.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
USH1G	Scaffold/PPI	no		SAM, Ankyrin_rpt, SAM/pointed_sf
PCDH15	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
esophagus squamous epithelium	1
lower esophagus mucosa	1
adrenal tissue	1
left adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
USH1G	69	broad	yes	lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis, esophagus squamous epithelium
PCDH15	130	tissue_specific	marker	left adrenal gland cortex, male germ line stem cell (sensu Vertebrata) in testis, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PCDH15	1,732
USH1G	1,354

Intra-cohort edges

A	B	Sources
PCDH15	USH1G	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PCDH15	Q96QU1	8
USH1G	Q495M9	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Sensory processing of sound by outer hair cells of the cochlea	2	203.9×	4e-05	USH1G, PCDH15
Sensory processing of sound by inner hair cells of the cochlea	2	163.1×	4e-05	USH1G, PCDH15

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
equilibrioception	2	2407.4×	1e-06	USH1G, PCDH15
sensory perception of light stimulus	2	1872.4×	1e-06	USH1G, PCDH15
photoreceptor cell maintenance	2	358.6×	3e-05	USH1G, PCDH15
sensory perception of sound	2	100.9×	2e-04	USH1G, PCDH15
regulation of clathrin-dependent endocytosis	1	842.6×	0.002	USH1G
inner ear receptor cell stereocilium organization	1	421.3×	0.004	USH1G
inner ear development	1	187.2×	0.008	PCDH15
inner ear morphogenesis	1	150.5×	0.008	USH1G
homophilic cell-cell adhesion	1	70.2×	0.016	PCDH15
cell adhesion	1	18.7×	0.053	PCDH15

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
USH1G	0	0
PCDH15	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PCDH15	9	Binding:9

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	USH1G, PCDH15

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
USH1G	0	—
PCDH15	9	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns