Retinal dystrophy and obesity

Summary

Retinal dystrophy and obesity (MONDO:0014522) is a disease caused by TUB (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: TUB (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 26

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinal dystrophy and obesity
Mondo ID	MONDO:0014522
OMIM	616188
UMLS	C4015424
MedGen	863861
GARD	0024998
Is cancer (heuristic)	no

Also known as: RDOB · retinal dystrophy and obesity

Data availability: 26 ClinVar variants · 5 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 › retinal dystrophy and obesity

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 39, 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, 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

26 retrieved; paginated sample, class counts are floors:

15 uncertain significance, 6 benign, 2 conflicting classifications of pathogenicity, 1 pathogenic, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
162490	NM_177972.3(TUB):c.1194_1195del (p.Arg398fs)	RIC3	Pathogenic	criteria provided, single submitter
804249	NM_177972.3(TUB):c.1215+1G>A	TUB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3780770	NM_177972.3(TUB):c.34dup (p.Tyr12fs)	TUB	Likely pathogenic	criteria provided, single submitter
1168423	NM_177972.3(TUB):c.1388-10T>G	RIC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1533591	NM_177972.3(TUB):c.885+7T>C	RIC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1010424	NM_177972.3(TUB):c.1159G>A (p.Val387Met)	RIC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1020820	NM_177972.3(TUB):c.451G>A (p.Val151Met)	RIC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1053687	NM_177972.3(TUB):c.728C>T (p.Pro243Leu)	RIC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1803813	NM_177972.3(TUB):c.722A>G (p.Glu241Gly)	RIC3	Uncertain significance	criteria provided, single submitter
2502171	NM_177972.3(TUB):c.1425G>C (p.Glu475Asp)	RIC3	Uncertain significance	criteria provided, single submitter
834503	NM_177972.3(TUB):c.293C>T (p.Ala98Val)	RIC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
839656	NM_177972.3(TUB):c.358G>A (p.Gly120Ser)	RIC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
933300	NM_177972.3(TUB):c.1498G>A (p.Asp500Asn)	RIC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
954012	NM_177972.3(TUB):c.1270G>A (p.Glu424Lys)	RIC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
956724	NM_177972.3(TUB):c.1210C>T (p.Arg404Cys)	RIC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
957947	NM_177972.3(TUB):c.1388C>T (p.Pro463Leu)	RIC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
962044	NM_177972.3(TUB):c.364G>A (p.Ala122Thr)	RIC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1043142	NM_177972.3(TUB):c.115AAG[2] (p.Lys41del)	TUB	Uncertain significance	criteria provided, multiple submitters, no conflicts
836922	NM_177972.3(TUB):c.164G>A (p.Arg55Gln)	TUB	Uncertain significance	criteria provided, multiple submitters, no conflicts
956702	NM_177972.3(TUB):c.1232T>A (p.Leu411Gln)	TUB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1170215	NM_177972.3(TUB):c.565+16A>G	RIC3	Benign	criteria provided, multiple submitters, no conflicts
1684222	NM_177972.3(TUB):c.397+26C>G	RIC3	Benign	criteria provided, multiple submitters, no conflicts
1684224	NM_177972.3(TUB):c.566-47C>G	RIC3	Benign	criteria provided, multiple submitters, no conflicts
1684230	NM_177972.3(TUB):c.566-32C>A	RIC3	Benign	criteria provided, multiple submitters, no conflicts
1684233	NM_177972.3(TUB):c.1388-22_1388-19del	RIC3	Benign	criteria provided, single submitter
1169389	NM_177972.3(TUB):c.360T>C (p.Gly120=)	TUB	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
TUB	Strong	Autosomal recessive	retinal dystrophy and obesity	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TUB	Orphanet:791	Retinitis pigmentosa

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
TUB	HGNC:12406	ENSG00000166402	P50607	Tubby protein homolog	gencc,clinvar
RIC3	HGNC:30338	ENSG00000166405	Q7Z5B4	Protein RIC-3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TUB	Tubby protein homolog	Functions in signal transduction from heterotrimeric G protein-coupled receptors.
RIC3	Protein RIC-3	Molecular chaperone which facilitates proper subunit assembly and surface trafficking of alpha-7 (CHRNA7) and alpha-8 (CHRNA8) nicotinic acetylcholine receptors.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TUB	Other/Unknown	no		Tubby_C, Tubby_N, Tubby_C_CS
RIC3	Other/Unknown	no		Ric3, RIC3_N

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
middle temporal gyrus	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1
adenohypophysis	1
left lobe of thyroid gland	1
right lobe of thyroid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TUB	240	ubiquitous	marker	substantia nigra pars reticulata, substantia nigra pars compacta, middle temporal gyrus
RIC3	178	broad	marker	adenohypophysis, left lobe of thyroid gland, right lobe of thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TUB	1,443
RIC3	1,103

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TUB	P50607	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RIC3	Q7Z5B4	58.55

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

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
receptor localization to non-motile cilium	1	1685.2×	0.005	TUB
protein localization to photoreceptor outer segment	1	1203.7×	0.005	TUB
phagocytosis, recognition	1	1053.2×	0.005	TUB
synaptic transmission, cholinergic	1	401.2×	0.008	RIC3
positive regulation of protein localization to cell surface	1	383.0×	0.008	RIC3
intraciliary transport	1	280.9×	0.008	TUB
protein localization to cell surface	1	247.8×	0.008	RIC3
protein localization to cilium	1	200.6×	0.008	TUB
regulation of G protein-coupled receptor signaling pathway	1	187.2×	0.008	TUB
photoreceptor cell maintenance	1	179.3×	0.008	TUB
positive regulation of phagocytosis	1	159.0×	0.009	TUB
retina development in camera-type eye	1	127.7×	0.010	TUB
positive regulation of cytosolic calcium ion concentration	1	58.5×	0.019	RIC3
protein-containing complex assembly	1	56.9×	0.019	RIC3
sensory perception of sound	1	50.5×	0.020	TUB

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
TUB	0	0
RIC3	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	0
E	Difficult family or no structure, no drug	2	TUB, RIC3

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)
TUB	0	—
RIC3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.