Retinitis pigmentosa 74

Summary

Retinitis pigmentosa 74 (MONDO:0014692) is a disease caused by BBS2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: BBS2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 221

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 74
Mondo ID	MONDO:0014692
OMIM	616562
DOID	DOID:0110401
UMLS	C4225281
MedGen	906896
GARD	0016138
Is cancer (heuristic)	no

Also known as: BBS2 retinitis pigmentosa · retinitis pigmentosa 74 · retinitis pigmentosa caused by mutation in BBS2 · retinitis pigmentosa type 74 · RP74

Data availability: 221 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 74

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, retinal dystrophy and obesity, retinitis pigmentosa 71, retinitis pigmentosa 72, retinitis pigmentosa 73, 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

221 retrieved; paginated sample, class counts are floors:

118 uncertain significance, 23 pathogenic/likely pathogenic, 21 likely benign, 20 likely pathogenic, 15 pathogenic, 14 conflicting classifications of pathogenicity, 7 benign/likely benign, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1066989	NM_031885.5(BBS2):c.1397+1G>A	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076595	NM_031885.5(BBS2):c.1649_1650del (p.Leu550fs)	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1378633	NM_031885.5(BBS2):c.255del (p.Glu86fs)	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1986519	NM_031885.5(BBS2):c.79A>C (p.Thr27Pro)	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208564	NM_031885.5(BBS2):c.661del (p.Leu221fs)	BBS2	Pathogenic	criteria provided, multiple submitters, no conflicts
209043	NM_031885.5(BBS2):c.401C>G (p.Pro134Arg)	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2093277	NM_031885.5(BBS2):c.717+1G>T	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217434	NM_031885.5(BBS2):c.263del (p.Gly88fs)	BBS2	Pathogenic	criteria provided, multiple submitters, no conflicts
284737	NM_031885.5(BBS2):c.1864C>T (p.Arg622Ter)	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382258	NM_031885.5(BBS2):c.1059dup (p.Asn354Ter)	BBS2	Pathogenic	criteria provided, single submitter
35754	NM_031885.5(BBS2):c.1015C>T (p.Arg339Ter)	BBS2	Pathogenic	criteria provided, multiple submitters, no conflicts
370943	NM_031885.5(BBS2):c.1237C>T (p.Arg413Ter)	BBS2	Pathogenic	criteria provided, multiple submitters, no conflicts
4569	NM_031885.5(BBS2):c.224T>G (p.Val75Gly)	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4570	NM_031885.5(BBS2):c.72C>G (p.Tyr24Ter)	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4571	NM_031885.5(BBS2):c.175C>T (p.Gln59Ter)	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4572	NM_031885.5(BBS2):c.823C>T (p.Arg275Ter)	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4573	NM_031885.5(BBS2):c.943C>T (p.Arg315Trp)	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4577	NM_031885.5(BBS2):c.311A>C (p.Asp104Ala)	BBS2	Pathogenic	criteria provided, multiple submitters, no conflicts
4578	NM_031885.5(BBS2):c.1895G>C (p.Arg632Pro)	BBS2	Pathogenic	criteria provided, multiple submitters, no conflicts
4580	NM_031885.5(BBS2):c.472del	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4583	NM_031885.5(BBS2):c.646C>T (p.Arg216Ter)	BBS2	Pathogenic	criteria provided, multiple submitters, no conflicts
496478	NM_031885.5(BBS2):c.2107C>T (p.Arg703Ter)	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
550489	NM_031885.5(BBS2):c.1780C>T (p.Arg594Ter)	BBS2	Pathogenic	criteria provided, multiple submitters, no conflicts
551008	NM_031885.5(BBS2):c.1705C>T (p.Gln569Ter)	BBS2	Pathogenic	criteria provided, multiple submitters, no conflicts
552219	NM_031885.5(BBS2):c.814C>T (p.Arg272Ter)	BBS2	Pathogenic	criteria provided, multiple submitters, no conflicts
552531	NM_031885.5(BBS2):c.563del (p.Ile188fs)	BBS2	Pathogenic	criteria provided, multiple submitters, no conflicts
553071	NM_031885.5(BBS2):c.717+1G>A	BBS2	Pathogenic	criteria provided, multiple submitters, no conflicts
553335	NM_031885.5(BBS2):c.1814C>G (p.Ser605Ter)	BBS2	Pathogenic	criteria provided, multiple submitters, no conflicts
553353	NM_031885.5(BBS2):c.1438C>T (p.Arg480Ter)	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
553927	NM_031885.5(BBS2):c.534+1G>T	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · 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
BBS2	Definitive	Autosomal recessive	retinitis pigmentosa 74	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BBS2	Orphanet:110	Bardet-Biedl syndrome
BBS2	Orphanet:791	Retinitis pigmentosa

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
BBS2	HGNC:967	ENSG00000125124	Q9BXC9	BBSome complex member BBS2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BBS2	BBSome complex member BBS2	The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BBS2	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, Bardet-Biedl_syndrome_2_prot, BBS2_GAE_dom

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
adrenal tissue	1
peripheral nervous system	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BBS2	262	ubiquitous	marker	adrenal tissue, right adrenal gland cortex, peripheral nervous system

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BBS2	1,824

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BBS2	Q9BXC9	89.49

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
BBSome-mediated cargo-targeting to cilium	1	496.5×	0.008	BBS2
Cargo trafficking to the periciliary membrane	1	248.3×	0.008	BBS2
Cilium Assembly	1	108.8×	0.012	BBS2
Organelle biogenesis and maintenance	1	66.0×	0.015	BBS2

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
negative regulation of appetite by leptin-mediated signaling pathway	1	4213.0×	0.004	BBS2
artery smooth muscle contraction	1	1872.4×	0.004	BBS2
regulation of cilium beat frequency involved in ciliary motility	1	1872.4×	0.004	BBS2
striatum development	1	1123.5×	0.004	BBS2
negative regulation of multicellular organism growth	1	1123.5×	0.004	BBS2
melanosome transport	1	766.0×	0.004	BBS2
brain morphogenesis	1	732.7×	0.004	BBS2
Golgi to plasma membrane protein transport	1	526.6×	0.004	BBS2
positive regulation of multicellular organism growth	1	495.6×	0.004	BBS2
sperm axoneme assembly	1	468.1×	0.004	BBS2
adult behavior	1	468.1×	0.004	BBS2
vasodilation	1	366.4×	0.005	BBS2
photoreceptor cell maintenance	1	358.6×	0.005	BBS2
non-motile cilium assembly	1	290.6×	0.006	BBS2
cartilage development	1	251.5×	0.006	BBS2
hippocampus development	1	230.8×	0.006	BBS2
cerebral cortex development	1	205.5×	0.007	BBS2
fat cell differentiation	1	181.2×	0.007	BBS2
intracellular protein localization	1	104.7×	0.012	BBS2
gene expression	1	79.9×	0.014	BBS2
visual perception	1	79.5×	0.014	BBS2
cilium assembly	1	73.6×	0.014	BBS2
negative regulation of gene expression	1	69.1×	0.014	BBS2

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
BBS2	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	BBS2

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)
BBS2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.