Retinitis pigmentosa 51

Summary

Retinitis pigmentosa 51 (MONDO:0013274) is a disease caused by TTC8 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: TTC8 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 134

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 51
Mondo ID	MONDO:0013274
OMIM	613464
DOID	DOID:0110398
UMLS	C3150715
MedGen	462065
GARD	0015665
Is cancer (heuristic)	no

Also known as: retinitis pigmentosa 51 · retinitis pigmentosa caused by mutation in TTC8 · retinitis pigmentosa type 51 · RP51 · TTC8 retinitis pigmentosa

Data availability: 134 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 51

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 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 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

134 retrieved; paginated sample, class counts are floors:

81 uncertain significance, 27 likely pathogenic, 9 pathogenic/likely pathogenic, 7 likely benign, 6 conflicting classifications of pathogenicity, 3 pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1213931	NM_144596.4(TTC8):c.1343_1347+17del	TTC8	Pathogenic	criteria provided, single submitter
1443806	NM_144596.4(TTC8):c.293del (p.Gly98fs)	TTC8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1694464	NM_144596.4(TTC8):c.265+1G>A	TTC8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2126790	NM_144596.4(TTC8):c.936del (p.Glu313fs)	TTC8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
235131	NM_144596.4(TTC8):c.1347G>C (p.Gln449His)	TTC8	Pathogenic	no assertion criteria provided
2415756	NM_144596.4(TTC8):c.677G>A (p.Trp226Ter)	TTC8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2428023	NM_144596.4(TTC8):c.256C>T (p.Gln86Ter)	TTC8	Pathogenic	criteria provided, multiple submitters, no conflicts
2530	NM_144596.4(TTC8):c.489G>A (p.Thr163=)	TTC8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2679373	NM_144596.4(TTC8):c.600dup (p.His201fs)	TTC8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3240668	NM_144596.4(TTC8):c.739C>T (p.Gln247Ter)	TTC8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
930561	NM_144596.4(TTC8):c.915del (p.Met305fs)	TTC8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
997900	NM_144596.4(TTC8):c.559C>T (p.Gln187Ter)	TTC8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1067170	NM_144596.4(TTC8):c.799-2A>G	TTC8	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2532	NM_144596.4(TTC8):c.115-2A>G	TTC8	Likely pathogenic	criteria provided, single submitter
2679368	NM_144596.4(TTC8):c.214G>T (p.Glu72Ter)	TTC8	Likely pathogenic	criteria provided, single submitter
2679369	NM_144596.4(TTC8):c.624+1_624+2del	TTC8	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2679370	NM_144596.4(TTC8):c.1348-1G>A	TTC8	Likely pathogenic	criteria provided, single submitter
2679371	NM_144596.4(TTC8):c.1224+1G>C	TTC8	Likely pathogenic	criteria provided, single submitter
2679372	NM_144596.4(TTC8):c.1132_1133del (p.Met378fs)	TTC8	Likely pathogenic	criteria provided, single submitter
2679374	NM_144596.4(TTC8):c.949G>T (p.Glu317Ter)	TTC8	Likely pathogenic	criteria provided, single submitter
2679375	NM_144596.4(TTC8):c.201_204del (p.Ile67fs)	TTC8	Likely pathogenic	criteria provided, single submitter
2679376	NM_144596.4(TTC8):c.638dup (p.Ala214fs)	TTC8	Likely pathogenic	criteria provided, single submitter
2679377	NM_144596.4(TTC8):c.1309dup (p.Leu437fs)	TTC8	Likely pathogenic	criteria provided, single submitter
2679378	NM_144596.4(TTC8):c.851del (p.Gly284fs)	TTC8	Likely pathogenic	criteria provided, single submitter
2679379	NM_144596.4(TTC8):c.94G>T (p.Glu32Ter)	TTC8	Likely pathogenic	criteria provided, single submitter
2679380	NM_144596.4(TTC8):c.823_839dup (p.Leu280_Phe281insTer)	TTC8	Likely pathogenic	criteria provided, single submitter
2679381	NM_144596.4(TTC8):c.265+1del	TTC8	Likely pathogenic	criteria provided, single submitter
2679383	NM_144596.4(TTC8):c.532_535del (p.Ser178fs)	TTC8	Likely pathogenic	criteria provided, single submitter
2679384	NM_144596.4(TTC8):c.1131_1135delinsC (p.Met378fs)	TTC8	Likely pathogenic	criteria provided, single submitter
3240664	NM_144596.4(TTC8):c.681G>A (p.Trp227Ter)	TTC8	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · 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
TTC8	Definitive	Autosomal recessive	retinitis pigmentosa 51	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TTC8	Orphanet:110	Bardet-Biedl syndrome
TTC8	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
TTC8	HGNC:20087	ENSG00000165533	Q8TAM2	Tetratricopeptide repeat protein 8	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TTC8	Tetratricopeptide repeat protein 8	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: 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)
TTC8	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, BBS8

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
islet of Langerhans	1
left ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TTC8	247	ubiquitous	marker	left ovary, islet of Langerhans, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TTC8	1,822

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TTC8	Q8TAM2	84.48

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
BBSome-mediated cargo-targeting to cilium	1	496.5×	0.002	TTC8

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
establishment of anatomical structure orientation	1	16852.0×	0.001	TTC8
sensory processing	1	5617.3×	0.001	TTC8
renal tubule development	1	4213.0×	0.001	TTC8
camera-type eye photoreceptor cell differentiation	1	3370.4×	0.001	TTC8
multi-ciliated epithelial cell differentiation	1	2808.7×	0.001	TTC8
establishment of planar polarity	1	1053.2×	0.002	TTC8
establishment of epithelial cell apical/basal polarity	1	1053.2×	0.002	TTC8
regulation of stress fiber assembly	1	991.3×	0.002	TTC8
inner ear receptor cell stereocilium organization	1	842.6×	0.002	TTC8
olfactory bulb development	1	766.0×	0.002	TTC8
non-motile cilium assembly	1	290.6×	0.006	TTC8
regulation of protein localization	1	205.5×	0.008	TTC8
fat cell differentiation	1	181.2×	0.008	TTC8
sensory perception of smell	1	156.0×	0.009	TTC8
multicellular organism growth	1	137.0×	0.009	TTC8
protein localization to plasma membrane	1	108.7×	0.011	TTC8
axon guidance	1	90.6×	0.012	TTC8
cilium assembly	1	73.6×	0.014	TTC8
protein transport	1	43.9×	0.023	TTC8

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
TTC8	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	TTC8

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)
TTC8	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.