Retinitis pigmentosa 39

Summary

Retinitis pigmentosa 39 (MONDO:0013436) is a disease caused by USH2A (GenCC Strong), with 4 cohort genes and 1 clinical trial.

At a glance

• Causal gene: USH2A (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 1,802
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 39
Mondo ID	MONDO:0013436
OMIM	613809
DOID	DOID:0110360
UMLS	C3151138
MedGen	462488
GARD	0015715
Is cancer (heuristic)	no

Also known as: retinitis pigmentosa 39 · retinitis pigmentosa caused by mutation in USH2A · retinitis pigmentosa type 39 · RP39 · USH2A retinitis pigmentosa

Data availability: 1,802 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › retinitis pigmentosa › retinitis pigmentosa 39

Related subtypes (101): retinitis pigmentosa 6, cone-rod dystrophy 2, retinitis pigmentosa 1, retinitis pigmentosa 9, retinitis pigmentosa 10, dominant pericentral pigmentary retinopathy, late-adult onset retinitis pigmentosa, autosomal recessive pericentral pigmentary retinopathy, retinitis pigmentosa 3, retinitis pigmentosa 24, retinitis pigmentosa 23, retinitis pigmentosa 34, retinitis pigmentosa 2, retinitis pigmentosa Y-linked, retinitis pigmentosa 13, retinitis pigmentosa 12, retinitis pigmentosa 14, retinitis pigmentosa 11, retinitis pigmentosa 17, retinitis pigmentosa 18, retinitis pigmentosa 19, retinitis pigmentosa 22, retinitis pigmentosa 25, retinitis pigmentosa 28, retinitis pigmentosa 30, retinitis pigmentosa 7, retinitis pigmentosa 26, retinitis pigmentosa 32, retinitis pigmentosa 31, retinitis pigmentosa 35, retinitis pigmentosa 33, retinitis pigmentosa 36, retinitis pigmentosa 37, retinitis pigmentosa 41, retinitis pigmentosa 29, retinitis pigmentosa 46, retinitis pigmentosa 42, retinitis pigmentosa 50, retinitis pigmentosa 54, retinitis pigmentosa 51, retinitis pigmentosa 55, retinitis pigmentosa 56, retinitis pigmentosa 57, retinitis pigmentosa 58, cone-rod dystrophy 15, retinitis pigmentosa 4, retinitis pigmentosa 27, retinitis pigmentosa 49, retinitis pigmentosa 47, retinitis pigmentosa 45, retinitis pigmentosa 44, retinitis pigmentosa 20, retinitis pigmentosa 40, retinitis pigmentosa 43, retinitis pigmentosa 48, retinitis pigmentosa 59, retinitis pigmentosa 38, retinitis pigmentosa 60, retinitis pigmentosa 61, retinitis pigmentosa 62, retinitis pigmentosa 63, cone-rod dystrophy 16, retinitis pigmentosa 66, retinitis pigmentosa with or without situs inversus, retinitis pigmentosa 67, retinitis pigmentosa 68, retinitis pigmentosa 69, retinitis pigmentosa 70, retinal dystrophy and obesity, retinitis pigmentosa 71, retinitis pigmentosa 72, retinitis pigmentosa 73, retinitis pigmentosa 74, retinitis pigmentosa 75, retinitis pigmentosa 76, retinitis pigmentosa 77, retinitis pigmentosa 92, retinitis pigmentosa 93, retinitis pigmentosa 83, retinitis pigmentosa 84, retinitis pigmentosa 85, retinitis pigmentosa 86, retinitis pigmentosa 87 with choroidal involvement, retinitis pigmentosa 88, retinitis pigmentosa 90, retinitis pigmentosa 81, retinitis pigmentosa 78, retinitis pigmentosa 79, retinitis pigmentosa 80, retinitis pigmentosa 94, variable age at onset, retinitis pigmentosa 53, retinitis pigmentosa 65, retinitis pigmentosa 64, retinitis pigmentosa 95, retinitis pigmentosa 96, retinitis pigmentosa 97, retinitis pigmentosa 98, retinitis pigmentosa 99, retinitis pigmentosa 100, retinitis pigmentosa 101, retinitis pigmentosa 7, digenic

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

600 retrieved; paginated sample, class counts are floors:

218 uncertain significance, 115 pathogenic/likely pathogenic, 69 pathogenic, 55 likely pathogenic, 50 likely benign, 47 conflicting classifications of pathogenicity, 26 benign/likely benign, 20 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1066803	NM_206933.4(USH2A):c.2809+1G>C	LOC122152296	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070807	NM_206933.4(USH2A):c.2649del (p.Glu883fs)	LOC122152296	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071995	NM_206933.4(USH2A):c.2525dup (p.Leu843fs)	LOC122152296	Pathogenic	criteria provided, multiple submitters, no conflicts
1213940	NM_206933.4(USH2A):c.2431_2432del (p.Lys811fs)	LOC122152296	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1352951	NM_206933.4(USH2A):c.2779C>T (p.Gln927Ter)	LOC122152296	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
143179	NM_206933.4(USH2A):c.2802T>G (p.Cys934Trp)	LOC122152296	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
166516	NM_206933.4(USH2A):c.2541C>A (p.Cys847Ter)	LOC122152296	Pathogenic	criteria provided, multiple submitters, no conflicts
2035651	NM_206933.4(USH2A):c.2670del (p.Ile891fs)	LOC122152296	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2043331	NM_206933.4(USH2A):c.2691C>A (p.Cys897Ter)	LOC122152296	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2107206	NM_206933.4(USH2A):c.2692C>T (p.Gln898Ter)	LOC122152296	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2679451	NM_206933.4(USH2A):c.2310dup (p.Glu771fs)	LOC122152296	Pathogenic	criteria provided, multiple submitters, no conflicts
2679465	NM_206933.4(USH2A):c.2440C>T (p.Gln814Ter)	LOC122152296	Pathogenic	criteria provided, single submitter
100610	NM_206933.4(USH2A):c.14792-2A>G	USH2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1016214	NM_206933.4(USH2A):c.13465G>A (p.Gly4489Ser)	USH2A	Pathogenic	criteria provided, multiple submitters, no conflicts
1024751	NM_206933.4(USH2A):c.12992A>G (p.Tyr4331Cys)	USH2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1033290	NM_206933.4(USH2A):c.4056G>A (p.Trp1352Ter)	USH2A	Pathogenic	criteria provided, single submitter
1051986	NM_206933.4(USH2A):c.4251G>T (p.Gln1417His)	USH2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1056888	NM_206933.4(USH2A):c.4124C>T (p.Ser1375Leu)	USH2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065666	NM_206933.4(USH2A):c.3828T>G (p.Tyr1276Ter)	USH2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065706	NM_206933.4(USH2A):c.4251+1G>T	USH2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065734	NM_206933.4(USH2A):c.14285A>G (p.Asn4762Ser)	USH2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065752	NM_206933.4(USH2A):c.4276_4277del (p.Glu1426fs)	USH2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065755	NM_206933.4(USH2A):c.3506G>A (p.Trp1169Ter)	USH2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065778	NM_206933.4(USH2A):c.11389+1G>T	USH2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068513	NM_206933.4(USH2A):c.8232del (p.Thr2743_Trp2744insTer)	USH2A	Pathogenic	criteria provided, multiple submitters, no conflicts
1069779	NM_206933.4(USH2A):c.4251+1del	USH2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070368	NM_206933.4(USH2A):c.6451del (p.Val2150_Leu2151insTer)	USH2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070462	NM_206933.4(USH2A):c.13131del (p.Pro4378fs)	USH2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070936	NM_206933.4(USH2A):c.9371+1G>A	USH2A	Pathogenic	criteria provided, multiple submitters, no conflicts
1071744	NM_206933.4(USH2A):c.6956del (p.Leu2319fs)	USH2A	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · 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
USH2A	Strong	Autosomal recessive	retinitis pigmentosa 39	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
USH2A	Orphanet:231178	Usher syndrome type 2
USH2A	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

4 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
USH2A	HGNC:12601	ENSG00000042781	O75445	Usherin	gencc,clinvar
KCTD3	HGNC:21305	ENSG00000136636	Q9Y597	BTB/POZ domain-containing protein KCTD3	clinvar
USH2A-AS2	HGNC:40605	ENSG00000233620		USH2A antisense RNA 2	clinvar
USH2A-AS1	HGNC:40606	ENSG00000236292		USH2A antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
USH2A	Usherin	Involved in hearing and vision as member of the USH2 complex.
KCTD3	BTB/POZ domain-containing protein KCTD3	Accessory subunit of potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) up-regulating its cell-surface expression and current density without affecting its voltage dependence and kinetics.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.25

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
Antibody/Immunoglobulin	1	7.3×	0.318
Scaffold/PPI	1	4.3×	0.318
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
USH2A	Antibody/Immunoglobulin	yes		Laminin_G, LE_dom, FN3_dom
KCTD3	Scaffold/PPI	no		BTB/POZ_dom, WD40_rpt, T1-type_BTB
USH2A-AS2	Other/Unknown	no
USH2A-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
right lobe of liver	1
jejunal mucosa	1
right adrenal gland	1
right adrenal gland cortex	1
anterior cingulate cortex	1
cerebellar vermis	1
quadriceps femoris	1
bone marrow	1
liver	1
spinal cord	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
USH2A	30	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, right lobe of liver, buccal mucosa cell
KCTD3	284	ubiquitous	marker	jejunal mucosa, right adrenal gland cortex, right adrenal gland
USH2A-AS2	54		yes	quadriceps femoris, anterior cingulate cortex, cerebellar vermis
USH2A-AS1	21		yes	liver, bone marrow, spinal cord

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
USH2A	2,332
KCTD3	1,222
USH2A-AS2	0
USH2A-AS1	0

Intra-cohort edges

A	B	Sources
KCTD3	USH2A	string_interaction

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KCTD3	Q9Y597	70.88
USH2A	O75445

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 4 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
CDC42 GTPase cycle	1	72.3×	0.037	KCTD3
RHO GTPase cycle	1	60.1×	0.037	KCTD3
Signaling by Rho GTPases	1	34.2×	0.037	KCTD3
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.037	KCTD3
Signal Transduction	1	10.2×	0.098	KCTD3

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
maintenance of animal organ identity	1	1685.2×	0.003	USH2A
inner ear receptor cell differentiation	1	1685.2×	0.003	USH2A
hair cell differentiation	1	1053.2×	0.003	USH2A
sensory perception of light stimulus	1	936.2×	0.003	USH2A
inner ear auditory receptor cell differentiation	1	601.9×	0.004	USH2A
establishment of protein localization	1	216.1×	0.008	USH2A
photoreceptor cell maintenance	1	179.3×	0.009	USH2A
establishment of localization in cell	1	80.2×	0.017	USH2A
protein homooligomerization	1	61.1×	0.020	KCTD3
sensory perception of sound	1	50.5×	0.022	USH2A
visual perception	1	39.8×	0.025	USH2A

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 4 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
USH2A	0	0
KCTD3	0	0
USH2A-AS2	0	0
USH2A-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	1	USH2A
E	Difficult family or no structure, no drug	3	KCTD3, USH2A-AS2, USH2A-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
USH2A	0	—
KCTD3	0	—
USH2A-AS2	0	—
USH2A-AS1	0	—

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
NCT03146078	Not specified	ACTIVE_NOT_RECRUITING	Rate of Progression in USH2A-related Retinal Degeneration