Bardet-Biedl syndrome 8

Summary

Bardet-Biedl syndrome 8 (MONDO:0014436) 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: 165

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bardet-Biedl syndrome 8
Mondo ID	MONDO:0014436
MeSH	C565917
OMIM	615985
DOID	DOID:0110130
UMLS	C1859566
MedGen	347181
GARD	0010207
Is cancer (heuristic)	no

Also known as: Bardet-Biedl syndrome 8 · Bardet-Biedl syndrome caused by mutation in TTC8 · Bardet-Biedl syndrome type 8 · BBS8 · TTC8 Bardet-Biedl syndrome

Data availability: 165 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Bardet-Biedl syndrome › Bardet-Biedl syndrome 8

Related subtypes (21): Bardet-Biedl syndrome 1, Bardet-Biedl syndrome 3, Bardet-Biedl syndrome 6, Bardet-Biedl syndrome 2, Bardet-Biedl syndrome 4, Bardet-Biedl syndrome 5, Bardet-Biedl syndrome 7, Bardet-Biedl syndrome 9, Bardet-Biedl syndrome 10, Bardet-Biedl syndrome 11, Bardet-Biedl syndrome 12, Bardet-Biedl syndrome 13, Bardet-Biedl syndrome 14, Bardet-Biedl syndrome 15, Bardet-Biedl syndrome 16, Bardet-Biedl syndrome 17, Bardet-Biedl syndrome 18, Bardet-Biedl syndrome 19, Bardet-Biedl syndrome 22, Bardet-Biedl syndrome 20, bardet-biedl syndrome 21

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

165 retrieved; paginated sample, class counts are floors:

105 uncertain significance, 24 conflicting classifications of pathogenicity, 10 likely pathogenic, 7 likely benign, 7 pathogenic/likely pathogenic, 7 pathogenic, 3 benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1443806	NM_144596.4(TTC8):c.293del (p.Gly98fs)	TTC8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1487906	NM_144596.4(TTC8):c.114+2T>C	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
2186475	NM_144596.4(TTC8):c.901_905del (p.Arg300_Ile301insTer)	TTC8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2528	NM_144596.4(TTC8):c.589_594del (p.Glu197_Tyr198del)	TTC8	Pathogenic	no assertion criteria provided
2529	NM_144596.4(TTC8):c.1049+2_1049+4del	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
2531	NM_144596.4(TTC8):c.624+1G>A	TTC8	Pathogenic	no assertion criteria provided
2577456	NM_144596.4(TTC8):c.114+1G>T	TTC8	Pathogenic	no assertion criteria provided
3075693	NM_144596.4(TTC8):c.1252C>T (p.Gln418Ter)	TTC8	Pathogenic	criteria provided, single submitter
3236396	NM_144596.4(TTC8):c.462_465del (p.Ser155fs)	TTC8	Pathogenic	criteria provided, single submitter
974367	NM_144596.4(TTC8):c.69del (p.Cys23fs)	TTC8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
974557	NM_198309.3:c.(768+1_769-1)_(879+1_880-1)del	TTC8	Pathogenic	criteria provided, single submitter
997900	NM_144596.4(TTC8):c.559C>T (p.Gln187Ter)	TTC8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2679369	NM_144596.4(TTC8):c.624+1_624+2del	TTC8	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3065384	NM_144596.4(TTC8):c.79dup (p.Cys27fs)	TTC8	Likely pathogenic	criteria provided, single submitter
3377639	NM_144596.4(TTC8):c.489+1G>A	TTC8	Likely pathogenic	criteria provided, single submitter
3576856	NM_144596.4(TTC8):c.340C>T (p.Gln114Ter)	TTC8	Likely pathogenic	criteria provided, single submitter
3576859	NM_144596.4(TTC8):c.456dup (p.Ser153fs)	TTC8	Likely pathogenic	criteria provided, single submitter
3576860	NM_144596.4(TTC8):c.502dup (p.Thr168fs)	TTC8	Likely pathogenic	criteria provided, single submitter
3576862	NM_144596.4(TTC8):c.580-2A>G	TTC8	Likely pathogenic	criteria provided, single submitter
3576866	NM_144596.4(TTC8):c.798+1G>A	TTC8	Likely pathogenic	criteria provided, single submitter
804470	NM_144596.4(TTC8):c.265+1_265+2del	TTC8	Likely pathogenic	criteria provided, single submitter
917966	NM_144596.4(TTC8):c.701G>A (p.Cys234Tyr)	TTC8	Likely pathogenic	no assertion criteria provided
100608	NM_144596.4(TTC8):c.625-5C>T	TTC8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1367817	NM_144596.4(TTC8):c.1420A>G (p.Ile474Val)	TTC8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1416630	NM_144596.4(TTC8):c.145-10T>C	TTC8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1593866	NM_144596.4(TTC8):c.625-12T>C	TTC8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
196599	NM_144596.4(TTC8):c.267C>A (p.Arg89=)	TTC8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
196600	NM_144596.4(TTC8):c.284A>G (p.Lys95Arg)	TTC8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

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	Bardet-Biedl syndrome 8	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.