Bardet-Biedl syndrome 16

Summary

Bardet-Biedl syndrome 16 (MONDO:0014444) is a disease caused by SDCCAG8 (GenCC Strong), with 5 cohort genes.

At a glance

• Causal gene: SDCCAG8 (GenCC Strong)
• Cohort genes: 5
• ClinVar variants: 644

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bardet-Biedl syndrome 16
Mondo ID	MONDO:0014444
OMIM	615993
DOID	DOID:0110138
UMLS	C3889474
MedGen	855172
GARD	0016040
Is cancer (heuristic)	no

Also known as: Bardet-Biedl syndrome 16 · Bardet-Biedl syndrome caused by mutation in SDCCAG8 · Bardet-Biedl syndrome type 16 · BBS16 · SDCCAG8 Bardet-Biedl syndrome

Data availability: 644 ClinVar variants · 3 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 16

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 10, Bardet-Biedl syndrome 11, Bardet-Biedl syndrome 12, Bardet-Biedl syndrome 13, Bardet-Biedl syndrome 14, Bardet-Biedl syndrome 15, 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

600 retrieved; paginated sample, class counts are floors:

270 uncertain significance, 207 likely benign, 38 pathogenic, 31 likely pathogenic, 28 conflicting classifications of pathogenicity, 11 pathogenic/likely pathogenic, 10 benign, 5 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2425626	NC_000001.10:g.(?243335979)(243419562_?)del	CEP170	Pathogenic	criteria provided, single submitter
660672	NC_000001.11:g.(?242268256)(243843190_?)del	CEP170	Pathogenic	criteria provided, single submitter
1070303	NM_006642.5(SDCCAG8):c.784G>T (p.Glu262Ter)	SDCCAG8	Pathogenic	criteria provided, multiple submitters, no conflicts
1071556	NM_006642.5(SDCCAG8):c.1147C>T (p.Gln383Ter)	SDCCAG8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1400329	NM_006642.5(SDCCAG8):c.250C>T (p.Gln84Ter)	SDCCAG8	Pathogenic	criteria provided, single submitter
1452529	NM_006642.5(SDCCAG8):c.234dup (p.Asp79fs)	SDCCAG8	Pathogenic	criteria provided, single submitter
1456221	NC_000001.10:g.(?243303219)(243456541_?)del	SDCCAG8	Pathogenic	criteria provided, single submitter
156528	NM_006642.5(SDCCAG8):c.1628_1631del (p.Asp543fs)	SDCCAG8	Pathogenic	no assertion criteria provided
156529	NM_006642.5(SDCCAG8):c.1444del (p.Thr482fs)	SDCCAG8	Pathogenic	criteria provided, multiple submitters, no conflicts
1909369	NM_006642.5(SDCCAG8):c.523G>T (p.Glu175Ter)	SDCCAG8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1918532	NM_006642.5(SDCCAG8):c.46C>T (p.Gln16Ter)	SDCCAG8	Pathogenic	criteria provided, single submitter
1955937	NM_006642.5(SDCCAG8):c.252del (p.Ala85fs)	SDCCAG8	Pathogenic	criteria provided, single submitter
2006501	NM_006642.5(SDCCAG8):c.629dup (p.Asn210fs)	SDCCAG8	Pathogenic	criteria provided, single submitter
2009850	NM_006642.5(SDCCAG8):c.849T>A (p.Cys283Ter)	SDCCAG8	Pathogenic	criteria provided, single submitter
2048826	NM_006642.5(SDCCAG8):c.397G>T (p.Glu133Ter)	SDCCAG8	Pathogenic	criteria provided, multiple submitters, no conflicts
2055381	NM_006642.5(SDCCAG8):c.553_554del (p.Met185fs)	SDCCAG8	Pathogenic	criteria provided, single submitter
212139	NM_006642.5(SDCCAG8):c.221-2A>G	SDCCAG8	Pathogenic	criteria provided, multiple submitters, no conflicts
212140	NM_006642.5(SDCCAG8):c.481C>T (p.Gln161Ter)	SDCCAG8	Pathogenic	criteria provided, multiple submitters, no conflicts
212141	NM_006642.5(SDCCAG8):c.567G>A (p.Trp189Ter)	SDCCAG8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2160069	NM_006642.5(SDCCAG8):c.82del (p.Ser28fs)	SDCCAG8	Pathogenic	criteria provided, single submitter
2203016	NM_006642.5(SDCCAG8):c.1068+1G>A	SDCCAG8	Pathogenic	criteria provided, single submitter
2633268	NM_006642.5(SDCCAG8):c.862C>T (p.Gln288Ter)	SDCCAG8	Pathogenic	criteria provided, single submitter
287667	NM_006642.5(SDCCAG8):c.1159del (p.Ala387fs)	SDCCAG8	Pathogenic	criteria provided, multiple submitters, no conflicts
2939244	NM_006642.5(SDCCAG8):c.1177del (p.Met392_Met393insTer)	SDCCAG8	Pathogenic	criteria provided, single submitter
2942587	NM_006642.5(SDCCAG8):c.1418dup (p.Glu474fs)	SDCCAG8	Pathogenic	criteria provided, single submitter
2951815	NM_006642.5(SDCCAG8):c.787C>T (p.Gln263Ter)	SDCCAG8	Pathogenic	criteria provided, single submitter
3247836	NC_000001.10:g.(?243419466)(243663097_?)del	SDCCAG8	Pathogenic	criteria provided, single submitter
3247837	NC_000001.10:g.(?243385006)(243480215_?)del	SDCCAG8	Pathogenic	criteria provided, single submitter
3247839	NC_000001.10:g.(?243433387)(243437978_?)del	SDCCAG8	Pathogenic	criteria provided, single submitter
3350620	NM_006642.5(SDCCAG8):c.511G>T (p.Glu171Ter)	SDCCAG8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 7 · 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
SDCCAG8	Strong	Autosomal recessive	Bardet-Biedl syndrome 16	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SDCCAG8	Orphanet:110	Bardet-Biedl syndrome
SDCCAG8	Orphanet:3156	Senior-Loken syndrome
AKT3	Orphanet:83473	Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome
AKT3	Orphanet:99802	Hemimegalencephaly
PDE11A	Orphanet:1359	Carney complex
PDE11A	Orphanet:647772	Isolated primary pigmented nodular adrenocortical disease
PDE11A	Orphanet:647782	Isolated micronodular adrenocortical disease

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SDCCAG8	HGNC:10671	ENSG00000054282	Q86SQ7	Serologically defined colon cancer antigen 8	gencc,clinvar
CATSPERE	HGNC:28491	ENSG00000179397	Q5SY80	Cation channel sperm-associated auxiliary subunit epsilon	clinvar
CEP170	HGNC:28920	ENSG00000143702	Q5SW79	Centrosomal protein of 170 kDa	clinvar
AKT3	HGNC:393	ENSG00000117020	Q9Y243	RAC-gamma serine/threonine-protein kinase	clinvar
PDE11A	HGNC:8773	ENSG00000128655	Q9HCR9	Dual 3’,5’-cyclic-AMP and -GMP phosphodiesterase 11A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SDCCAG8	Serologically defined colon cancer antigen 8	Plays a role in the establishment of cell polarity and epithelial lumen formation.
CATSPERE	Cation channel sperm-associated auxiliary subunit epsilon	Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation.
CEP170	Centrosomal protein of 170 kDa	Plays a role in microtubule organization.
AKT3	RAC-gamma serine/threonine-protein kinase	AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis.
PDE11A	Dual 3’,5’-cyclic-AMP and -GMP phosphodiesterase 11A	Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides cAMP and cGMP.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.4

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
Antibody/Immunoglobulin	1	5.8×	0.336
Kinase	1	5.5×	0.336
Transcription factor	1	1.6×	0.634
Other/Unknown	2	0.7×	0.877

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SDCCAG8	Other/Unknown	no		SDCCAG8
CATSPERE	Antibody/Immunoglobulin	yes		CATSPERD/E, CATSPERD/E_C, CATSPERE_Ig-like
CEP170	Other/Unknown	no		FHA_dom, SMAD_FHA_dom_sf, CEP170_C
AKT3	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, PH_domain
PDE11A	Transcription factor	no	3.1.4.17	PDEase_catalytic_dom, GAF, HD/PDEase_dom

Expression context

Cohort genes with no expression data: 0.

5 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
corpus callosum	2
cortical plate	2
thyroid gland	1
left testis	1
primordial germ cell in gonad	1
right testis	1
ganglionic eminence	1
embryo	1
deltoid	1
quadriceps femoris	1
vastus lateralis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SDCCAG8	134	ubiquitous	marker	corpus callosum, calcaneal tendon, thyroid gland
CATSPERE	166	broad	marker	primordial germ cell in gonad, left testis, right testis
CEP170	134	ubiquitous	marker	cortical plate, ganglionic eminence, corpus callosum
AKT3	231	ubiquitous	marker	cortical plate, calcaneal tendon, embryo
PDE11A	166	broad	marker	deltoid, quadriceps femoris, vastus lateralis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AKT3	3,392
CEP170	2,543
SDCCAG8	1,837
PDE11A	778
CATSPERE	551

Structural data

PDB: 2 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AKT3	Q9Y243	2
CEP170	Q5SW79	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CATSPERE	Q5SY80	89.01
PDE11A	Q9HCR9	79.12
SDCCAG8	Q86SQ7	78.67

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 99. Enrichment computed across 5 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
AKT-mediated inactivation of FOXO1A	1	951.7×	0.027	AKT3
Inhibition of TSC complex formation by AKT (PKB)	1	761.3×	0.027	AKT3
G-protein beta:gamma signalling	1	634.4×	0.027	AKT3
RUNX2 regulates genes involved in cell migration	1	475.8×	0.027	AKT3
AKT phosphorylates targets in the nucleus	1	380.7×	0.027	AKT3
Regulation of localization of FOXO transcription factors	1	317.2×	0.027	AKT3
SARS-CoV-2 targets host intracellular signalling and regulatory pathways	1	292.8×	0.027	AKT3
Downregulation of ERBB2:ERBB3 signaling	1	271.9×	0.027	AKT3
AKT phosphorylates targets in the cytosol	1	271.9×	0.027	AKT3
Regulation of TP53 Activity through Association with Co-factors	1	271.9×	0.027	AKT3
Activation of BAD and translocation to mitochondria	1	253.8×	0.027	AKT3
Regulation of beta-cell development	1	237.9×	0.027	AKT3
cGMP effects	1	237.9×	0.027	PDE11A
Regulation of gene expression in beta cells	1	173.0×	0.027	AKT3
Co-inhibition by CTLA4	1	173.0×	0.027	AKT3
Regulation of TP53 Expression and Degradation	1	173.0×	0.027	AKT3
Activation of BH3-only proteins	1	165.5×	0.027	AKT3
Regulation of TP53 Activity through Acetylation	1	152.3×	0.027	AKT3
G beta:gamma signalling through PI3Kgamma	1	146.4×	0.027	AKT3
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	1	146.4×	0.027	AKT3
Regulation of T cell activation by CD28 family	1	141.0×	0.027	AKT3
Constitutive Signaling by AKT1 E17K in Cancer	1	141.0×	0.027	AKT3
VEGFR2 mediated vascular permeability	1	135.9×	0.027	AKT3
CD28 dependent PI3K/Akt signaling	1	131.3×	0.027	AKT3
Co-stimulation by CD28	1	126.9×	0.027	AKT3
Downregulation of ERBB2 signaling	1	126.9×	0.027	AKT3
PI3K/AKT Signaling in Cancer	1	122.8×	0.027	AKT3
Rab regulation of trafficking	1	122.8×	0.027	AKT3
Signaling by ERBB2	1	115.3×	0.027	AKT3
FLT3 Signaling	1	115.3×	0.027	AKT3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of artery morphogenesis	1	842.6×	0.013	AKT3
negative regulation of receptor guanylyl cyclase signaling pathway	1	702.2×	0.013	PDE11A
tube formation	1	526.6×	0.013	SDCCAG8
microtubule organizing center organization	1	351.1×	0.013	SDCCAG8
negative regulation of PERK-mediated unfolded protein response	1	351.1×	0.013	AKT3
positive regulation of cell size	1	324.1×	0.013	AKT3
regulation of mitochondrion organization	1	210.7×	0.013	AKT3
positive regulation of vascular endothelial cell proliferation	1	210.7×	0.013	AKT3
brain morphogenesis	1	183.2×	0.013	AKT3
positive regulation of cell migration involved in sprouting angiogenesis	1	183.2×	0.013	AKT3
sperm capacitation	1	168.5×	0.013	CATSPERE
negative regulation of cellular senescence	1	162.0×	0.013	AKT3
negative regulation of cAMP/PKA signal transduction	1	150.5×	0.013	PDE11A
regulation of cilium assembly	1	150.5×	0.013	SDCCAG8
positive regulation of TOR signaling	1	123.9×	0.015	AKT3
homeostasis of number of cells within a tissue	1	110.9×	0.016	AKT3
positive regulation of blood vessel endothelial cell migration	1	98.0×	0.016	AKT3
establishment of cell polarity	1	95.8×	0.016	SDCCAG8
cell projection organization	1	93.6×	0.016	SDCCAG8
centrosome cycle	1	84.3×	0.017	SDCCAG8
positive regulation of endothelial cell proliferation	1	57.7×	0.023	AKT3
insulin receptor signaling pathway	1	55.4×	0.023	AKT3
signal transduction	2	8.0×	0.026	AKT3, PDE11A
neuron migration	1	33.4×	0.035	SDCCAG8
flagellated sperm motility	1	29.3×	0.037	CATSPERE
positive regulation of angiogenesis	1	28.9×	0.037	AKT3
intracellular signal transduction	1	9.5×	0.105	AKT3
negative regulation of apoptotic process	1	8.7×	0.110	AKT3

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 5 evidence-associated genes (60%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
AKT3	CAPIVASERTIB
PDE11A	VARDENAFIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AKT3	18	4
PDE11A	7	4
SDCCAG8	0	0
CATSPERE	0	0
CEP170	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CAPIVASERTIB	4	AKT3
MIDOSTAURIN	4	AKT3
VARDENAFIL	4	PDE11A
SILDENAFIL	4	PDE11A
TADALAFIL	4	PDE11A
DIPYRIDAMOLE	4	PDE11A
IPATASERTIB	3	AKT3
AFURESERTIB	3	AKT3
ENZASTAURIN	3	AKT3
FASUDIL	3	AKT3
LESTAURTINIB	3	AKT3
RUBOXISTAURIN	3	AKT3
MIRANSERTIB	2	AKT3
MK-2206	2	AKT3
UPROSERTIB	2	AKT3
ZAPRINAST	2	PDE11A
AT-13148	1	AKT3
GSK-690693	1	AKT3
GSK-1070916	1	AKT3
JNJ-26483327	1	AKT3
PF-03758309	1	AKT3
BAY-1125976	1	AKT3
VEVORISERTIB	1	AKT3
JNJ-42396302	1	PDE11A
LENRISPODUN PHOSPHATE	1	PDE11A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
AKT3	660	Binding:644, Functional:16
PDE11A	142	Binding:135, ADMET:5, Functional:1, Toxicity:1
CEP170	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AKT3	2.7.11.1	non-specific serine/threonine protein kinase
PDE11A	3.1.4.17	3’,5’-cyclic-nucleotide phosphodiesterase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
AKT3	660
PDE11A	142

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

25 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.

Compound	Max phase	Cohort target (bioactivity)
CAPIVASERTIB	4	AKT3
MIDOSTAURIN	4	AKT3
VARDENAFIL	4	PDE11A
SILDENAFIL	4	PDE11A
TADALAFIL	4	PDE11A
DIPYRIDAMOLE	4	PDE11A
IPATASERTIB	3	AKT3
AFURESERTIB	3	AKT3
ENZASTAURIN	3	AKT3
FASUDIL	3	AKT3
LESTAURTINIB	3	AKT3
RUBOXISTAURIN	3	AKT3
MIRANSERTIB	2	AKT3
MK-2206	2	AKT3
UPROSERTIB	2	AKT3
ZAPRINAST	2	PDE11A
AT-13148	1	AKT3
GSK-690693	1	AKT3
GSK-1070916	1	AKT3
JNJ-26483327	1	AKT3
PF-03758309	1	AKT3
BAY-1125976	1	AKT3
VEVORISERTIB	1	AKT3
JNJ-42396302	1	PDE11A
LENRISPODUN PHOSPHATE	1	PDE11A

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	AKT3, PDE11A
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	CATSPERE
E	Difficult family or no structure, no drug	2	SDCCAG8, CEP170

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SDCCAG8	0	—
CATSPERE	0	—
CEP170	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.