Bardet-Biedl syndrome 14

Summary

Bardet-Biedl syndrome 14 (MONDO:0014442) is a disease caused by CEP290 (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: CEP290 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 1,245

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bardet-Biedl syndrome 14
Mondo ID	MONDO:0014442
MeSH	C567141
OMIM	615991
DOID	DOID:0110136
UMLS	C2673874
MedGen	393033
GARD	0016038
Is cancer (heuristic)	no

Also known as: Bardet-Biedl syndrome 14 · Bardet-Biedl syndrome 14, modifier of · Bardet-Biedl syndrome type 14 · BBS14

Data availability: 1,245 ClinVar variants · 2 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 14

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 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

600 retrieved; paginated sample, class counts are floors:

199 uncertain significance, 121 pathogenic/likely pathogenic, 93 likely pathogenic, 60 conflicting classifications of pathogenicity, 59 pathogenic, 47 likely benign, 12 benign/likely benign, 9 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1032903	NM_025114.4(CEP290):c.2632del (p.Ile878fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069520	NM_025114.4(CEP290):c.3488_3494dup (p.Val1166fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069579	NM_025114.4(CEP290):c.5235_5238del (p.Ser1745fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069582	NM_025114.4(CEP290):c.4090G>T (p.Glu1364Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
1069639	NM_025114.4(CEP290):c.1668del (p.Arg557fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070003	NM_025114.4(CEP290):c.6487dup (p.Met2163fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070250	NM_025114.4(CEP290):c.3925C>T (p.Gln1309Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070783	NM_025114.4(CEP290):c.6624del (p.Arg2208fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071036	NM_025114.4(CEP290):c.3708dup (p.Arg1237fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071060	NM_025114.4(CEP290):c.2506_2507del (p.Glu836fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071061	NM_025114.4(CEP290):c.1987A>T (p.Lys663Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
1071248	NM_025114.4(CEP290):c.5136_5139del (p.Glu1713fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071318	NM_025114.4(CEP290):c.7287T>A (p.Tyr2429Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071910	NM_025114.4(CEP290):c.7324G>T (p.Glu2442Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071911	NM_025114.4(CEP290):c.1254_1255del (p.Lys419fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073010	NM_025114.4(CEP290):c.955del (p.Ser319fs)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
1073163	NM_025114.4(CEP290):c.307C>T (p.Gln103Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073200	NM_025114.4(CEP290):c.1060C>T (p.Gln354Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074154	NM_025114.4(CEP290):c.532C>T (p.Gln178Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074481	NM_025114.4(CEP290):c.1258dup (p.Thr420fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074486	NM_025114.4(CEP290):c.4983del (p.Lys1661_Val1662insTer)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074543	NM_025114.4(CEP290):c.5788_5792del (p.Lys1930fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074952	NM_025114.4(CEP290):c.2213del (p.Asn737_Leu738insTer)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075280	NM_025114.4(CEP290):c.583_584del (p.Leu195fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075391	NM_025114.4(CEP290):c.5941G>T (p.Glu1981Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075924	NM_025114.4(CEP290):c.7282_7283dup (p.Tyr2429fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1098750	NM_025114.4(CEP290):c.384_385del (p.Asp128fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1185813	NM_025114.4(CEP290):c.712G>T (p.Glu238Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
126260	NM_025114.4(CEP290):c.4621del (p.Thr1541fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324056	NM_025114.4(CEP290):c.3167C>A (p.Ser1056Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 10 · 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
CEP290	Strong	Autosomal recessive	Bardet-Biedl syndrome 14	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CEP290	Orphanet:110	Bardet-Biedl syndrome
CEP290	Orphanet:2318	Joubert syndrome with oculorenal defect
CEP290	Orphanet:3156	Senior-Loken syndrome
CEP290	Orphanet:564	Meckel syndrome
CEP290	Orphanet:65	Leber congenital amaurosis
TMEM67	Orphanet:140976	RHYNS syndrome
TMEM67	Orphanet:1454	Joubert syndrome with hepatic defect
TMEM67	Orphanet:475	Isolated Joubert syndrome
TMEM67	Orphanet:564	Meckel syndrome
TMEM67	Orphanet:84081	Senior-Boichis syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CEP290	HGNC:29021	ENSG00000198707	O15078	Centrosomal protein of 290 kDa	gencc,clinvar
RLIG1	HGNC:25322	ENSG00000133641	Q8N999	RNA ligase 1	clinvar
TMEM67	HGNC:28396	ENSG00000164953	Q5HYA8	Meckelin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CEP290	Centrosomal protein of 290 kDa	Involved in early and late steps in cilia formation.
RLIG1	RNA ligase 1	Functions as an RNA ligase, in vitro.
TMEM67	Meckelin	Required for ciliary structure and function.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CEP290	Other/Unknown	no		Cep290, Cep209_CC5
RLIG1	Other/Unknown	no		RLIG1
TMEM67	Other/Unknown	no		Growth_fac_rcpt_cys_sf, Meckelin

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right uterine tube	2
male germ line stem cell (sensu Vertebrata) in testis	1
ventricular zone	1
Brodmann (1909) area 23	1
endothelial cell	1
oocyte	1
buccal mucosa cell	1
calcaneal tendon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CEP290	278	ubiquitous	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, ventricular zone
RLIG1	288	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, oocyte
TMEM67	203	ubiquitous	marker	buccal mucosa cell, right uterine tube, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CEP290	2,778
TMEM67	1,194
RLIG1	506

Intra-cohort edges

A	B	Sources
CEP290	TMEM67	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TMEM67	Q5HYA8	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RLIG1	Q8N999	92.03
CEP290	O15078	60.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 3 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
Anchoring of the basal body to the plasma membrane	2	113.1×	8e-04	CEP290, TMEM67
Cilium Assembly	2	108.8×	8e-04	CEP290, TMEM67
Organelle biogenesis and maintenance	2	66.0×	0.001	CEP290, TMEM67
Centrosome maturation	1	126.9×	0.027	CEP290
Loss of Nlp from mitotic centrosomes	1	79.3×	0.027	CEP290
Loss of proteins required for interphase microtubule organization from the centrosome	1	79.3×	0.027	CEP290
AURKA Activation by TPX2	1	76.1×	0.027	CEP290
Recruitment of mitotic centrosome proteins and complexes	1	68.0×	0.027	CEP290
Regulation of PLK1 Activity at G2/M Transition	1	63.4×	0.027	CEP290
Mitotic G2-G2/M phases	1	63.4×	0.027	CEP290
G2/M Transition	1	63.4×	0.027	CEP290
Recruitment of NuMA to mitotic centrosomes	1	58.3×	0.027	CEP290
Mitotic Prometaphase	1	34.6×	0.041	CEP290
M Phase	1	33.0×	0.041	CEP290
Cell Cycle, Mitotic	1	24.1×	0.052	CEP290
Cell Cycle	1	18.0×	0.065	CEP290
Innate Immune System	1	12.8×	0.086	CEP290
Neutrophil degranulation	1	11.5×	0.090	CEP290
Immune System	1	6.5×	0.148	CEP290

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete ciliary basal body-plasma membrane docking	1	2808.7×	0.003	CEP290
RNA repair	1	1872.4×	0.003	RLIG1
ciliary transition zone assembly	1	1872.4×	0.003	CEP290
cilium assembly	2	49.1×	0.003	CEP290, TMEM67
negative regulation of centrosome duplication	1	1123.5×	0.004	TMEM67
pronephros development	1	802.5×	0.004	CEP290
regulation of establishment of protein localization	1	802.5×	0.004	CEP290
otic vesicle formation	1	702.2×	0.004	CEP290
hindbrain development	1	374.5×	0.006	CEP290
response to reactive oxygen species	1	351.1×	0.006	RLIG1
eye photoreceptor cell development	1	280.9×	0.006	CEP290
positive regulation of intracellular protein transport	1	224.7×	0.007	CEP290
non-canonical Wnt signaling pathway	1	193.7×	0.008	TMEM67
camera-type eye development	1	119.5×	0.012	CEP290
non-motile cilium assembly	1	96.8×	0.014	CEP290
hematopoietic progenitor cell differentiation	1	79.1×	0.016	RLIG1
ERAD pathway	1	60.4×	0.019	TMEM67
kidney development	1	46.8×	0.024	CEP290
protein transport	1	14.6×	0.070	CEP290
positive regulation of DNA-templated transcription	1	9.3×	0.104	CEP290

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 0 of 3 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
CEP290	0	0
RLIG1	0	0
TMEM67	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	CEP290, RLIG1, TMEM67

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)
CEP290	0	—
RLIG1	0	—
TMEM67	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.