Bardet-Biedl syndrome 10

Summary

Bardet-Biedl syndrome 10 (MONDO:0014438) is a disease caused by BBS10 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: BBS10 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 475

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bardet-Biedl syndrome 10
Mondo ID	MONDO:0014438
MeSH	C565919
OMIM	615987
DOID	DOID:0110132
UMLS	C1859568
MedGen	347909
GARD	0010209
Is cancer (heuristic)	no

Also known as: Bardet-Biedl syndrome 10 · Bardet-Biedl syndrome caused by mutation in BBS10 · Bardet-Biedl syndrome type 10 · BBS10 · BBS10 Bardet-Biedl syndrome

Data availability: 475 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 10

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 8, Bardet-Biedl syndrome 9, 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

475 retrieved; paginated sample, class counts are floors:

193 uncertain significance, 92 likely pathogenic, 65 pathogenic/likely pathogenic, 42 conflicting classifications of pathogenicity, 38 pathogenic, 30 likely benign, 11 benign, 4 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1029918	NM_024685.4(BBS10):c.1365T>G (p.Tyr455Ter)	BBS10	Pathogenic	criteria provided, multiple submitters, no conflicts
1073736	NM_024685.4(BBS10):c.1654G>T (p.Gly552Ter)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179122	NM_024685.4(BBS10):c.9_15delinsGC (p.Ser3fs)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1210363	NM_024685.4(BBS10):c.235del (p.Thr79fs)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1328	NM_024685.4(BBS10):c.271dup (p.Cys91fs)	BBS10	Pathogenic	criteria provided, multiple submitters, no conflicts
1331	NM_024685.4(BBS10):c.931T>G (p.Ser311Ala)	BBS10	Pathogenic	criteria provided, multiple submitters, no conflicts
1333503	NM_024685.4(BBS10):c.804_805del (p.Ser269fs)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1361644	NM_024685.4(BBS10):c.310_311del (p.Glu104fs)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1366812	NM_024685.4(BBS10):c.1814_1815del (p.Asn605fs)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1380281	NM_024685.4(BBS10):c.1556_1557del (p.Thr519fs)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1432412	NM_024685.4(BBS10):c.793C>T (p.Gln265Ter)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453738	NM_024685.4(BBS10):c.1335_1338del (p.Tyr448fs)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456454	NM_024685.4(BBS10):c.340del (p.Gln114fs)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457055	NM_024685.4(BBS10):c.84C>A (p.Cys28Ter)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457503	NM_024685.4(BBS10):c.963T>G (p.Tyr321Ter)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
166723	NM_024685.4(BBS10):c.1091del (p.Asn364fs)	BBS10	Pathogenic	criteria provided, multiple submitters, no conflicts
1801520	NM_024685.4(BBS10):c.805dup (p.Ser269fs)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188941	NM_024685.4(BBS10):c.1184dup (p.His395fs)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188943	NM_024685.4(BBS10):c.1241T>C (p.Leu414Ser)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188992	NM_024685.4(BBS10):c.1599_1602del (p.Thr534fs)	BBS10	Pathogenic	criteria provided, multiple submitters, no conflicts
189071	NM_024685.4(BBS10):c.728_731del (p.Lys243fs)	BBS10	Pathogenic	criteria provided, multiple submitters, no conflicts
189107	NM_024685.4(BBS10):c.1448_1452del (p.Thr483fs)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2136306	NM_024685.4(BBS10):c.180dup (p.Glu61fs)	BBS10	Pathogenic	criteria provided, multiple submitters, no conflicts
2137392	NM_024685.4(BBS10):c.391del (p.Gln131fs)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
216123	NM_024685.4(BBS10):c.687del (p.Val230fs)	BBS10	Pathogenic	criteria provided, multiple submitters, no conflicts
216124	NM_024685.4(BBS10):c.531C>A (p.Tyr177Ter)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217438	NM_024685.4(BBS10):c.1856_1865del (p.Lys619fs)	BBS10	Pathogenic	no assertion criteria provided
217439	NM_024685.4(BBS10):c.1024dup (p.Ile342fs)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217440	NM_024685.4(BBS10):c.1547del (p.Thr516fs)	BBS10	Pathogenic	criteria provided, single submitter
225010	NM_024685.4(BBS10):c.145C>T (p.Arg49Trp)	BBS10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
BBS10	Definitive	Autosomal recessive	Bardet-Biedl syndrome 10	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BBS10	Orphanet:110	Bardet-Biedl syndrome
NADK2	Orphanet:431361	Progressive encephalopathy with leukodystrophy due to DECR deficiency

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
BBS10	HGNC:26291	ENSG00000179941	Q8TAM1	BBSome complex assembly protein BBS10	gencc,clinvar
NADK2	HGNC:26404	ENSG00000152620	Q4G0N4	NAD kinase 2, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BBS10	BBSome complex assembly protein BBS10	Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis.
NADK2	NAD kinase 2, mitochondrial	Mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BBS10	Other/Unknown	no		Cpn60/GroEL/TCP-1, GroEL-like_apical_dom_sf, TCP-1-like_intermed_sf
NADK2	Kinase	yes	2.7.1.23	NADK, NADK2_mit, NAD/diacylglycerol_kinase_sf

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
endothelial cell	1
ventricular zone	1
epithelial cell of pancreas	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BBS10	253	ubiquitous	yes	calcaneal tendon, endothelial cell, ventricular zone
NADK2	258	ubiquitous	marker	liver, right lobe of liver, epithelial cell of pancreas

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BBS10	3,224
NADK2	778

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NADK2	Q4G0N4	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BBS10	Q8TAM1	71.26

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 2 evidence-associated genes (2 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 2 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	248.3×	0.025	BBS10
Nicotinate metabolism	1	196.9×	0.025	NADK2
Cargo trafficking to the periciliary membrane	1	124.1×	0.026	BBS10
Metabolism of water-soluble vitamins and cofactors	1	90.6×	0.026	NADK2
Metabolism of vitamins and cofactors	1	58.3×	0.026	NADK2
Mitochondrial protein degradation	1	57.1×	0.026	NADK2
Cilium Assembly	1	54.4×	0.026	BBS10
Organelle biogenesis and maintenance	1	33.0×	0.038	BBS10
Metabolism of proteins	1	6.2×	0.165	NADK2
Metabolism	1	5.8×	0.165	NADK2

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
retinal cone cell differentiation	1	2808.7×	0.003	BBS10
cone retinal bipolar cell differentiation	1	2106.5×	0.003	BBS10
NADP+ biosynthetic process	1	1203.7×	0.003	NADK2
NAD+ metabolic process	1	936.2×	0.003	NADK2
retinal rod cell differentiation	1	936.2×	0.003	BBS10
response to light stimulus	1	443.5×	0.005	BBS10
regulation of protein-containing complex assembly	1	366.4×	0.005	BBS10
chaperone-mediated protein complex assembly	1	351.1×	0.005	BBS10
neuronal action potential	1	240.7×	0.007	BBS10
photoreceptor cell maintenance	1	179.3×	0.008	BBS10
non-motile cilium assembly	1	145.3×	0.009	BBS10
response to endoplasmic reticulum stress	1	83.4×	0.015	BBS10
negative regulation of neuron apoptotic process	1	55.4×	0.020	BBS10
intracellular protein localization	1	52.3×	0.020	BBS10
visual perception	1	39.8×	0.025	BBS10

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
BBS10	0	0
NADK2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NADK2	2.7.1.23	NAD+ kinase

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	1	NADK2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	BBS10

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)
BBS10	0	—
NADK2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.