Bardet-Biedl syndrome 6

Summary

Bardet-Biedl syndrome 6 (MONDO:0011523) is a disease caused by MKKS (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MKKS (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 222

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bardet-Biedl syndrome 6
Mondo ID	MONDO:0011523
MeSH	C565738
OMIM	605231
DOID	DOID:0110128
UMLS	C1858054
MedGen	347610
GARD	0010205
Is cancer (heuristic)	no

Also known as: Bardet-Biedl syndrome 6 · Bardet-Biedl syndrome type 6 · BBS6

Data availability: 222 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 6

Related subtypes (21): Bardet-Biedl syndrome 1, Bardet-Biedl syndrome 3, 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 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

222 retrieved; paginated sample, class counts are floors:

104 uncertain significance, 28 conflicting classifications of pathogenicity, 28 likely pathogenic, 27 pathogenic/likely pathogenic, 11 likely benign, 11 pathogenic, 7 benign/likely benign, 6 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1066030	NM_170784.3(MKKS):c.1034G>A (p.Gly345Glu)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074439	NM_170784.3(MKKS):c.63_64del (p.Arg21fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179069	NM_170784.3(MKKS):c.986-1G>A	MKKS	Pathogenic	criteria provided, multiple submitters, no conflicts
1297700	NM_170784.3(MKKS):c.1436C>G (p.Ser479Ter)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1406457	NM_170784.3(MKKS):c.867dup (p.Leu290fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1431638	NM_170784.3(MKKS):c.940_941del (p.Asp314fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457941	NM_170784.3(MKKS):c.515_516del (p.Glu172fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1683700	NM_170784.3(MKKS):c.429_434delinsTT (p.Phe144fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1712273	NM_170784.3(MKKS):c.950_960del (p.Gly317fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2056365	NM_170784.3(MKKS):c.432dup (p.Ser145Ter)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2158742	NM_170784.3(MKKS):c.942_945del (p.Asp314fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2676533	NM_170784.3(MKKS):c.221T>G (p.Leu74Ter)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2676536	NM_170784.3(MKKS):c.1410_1413del (p.Thr470_Asp471insTer)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2676539	NM_170784.3(MKKS):c.966del (p.Glu322fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2676540	NM_170784.3(MKKS):c.1434G>A (p.Trp478Ter)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2928460	NM_170784.3(MKKS):c.257C>A (p.Ser86Ter)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3241927	NM_170784.3(MKKS):c.1192C>T (p.Gln398Ter)	MKKS	Pathogenic	criteria provided, single submitter
3385244	NM_170784.3(MKKS):c.1310_1311del (p.Glu437fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3587030	NM_170784.3(MKKS):c.1368del (p.Val457fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
478890	NM_170784.3(MKKS):c.250C>T (p.His84Tyr)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
521251	NM_170784.3(MKKS):c.845dup (p.Leu283fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
522402	NM_170784.3(MKKS):c.613A>T (p.Lys205Ter)	MKKS	Pathogenic	no assertion criteria provided
5309	NM_170784.3(MKKS):c.110A>G (p.Tyr37Cys)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5311	NM_170784.3(MKKS):c.155G>A (p.Gly52Asp)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5312	NM_170784.3(MKKS):c.792T>A (p.Tyr264Ter)	MKKS	Pathogenic	no assertion criteria provided
5313	NM_170784.3(MKKS):c.281del (p.Phe94fs)	MKKS	Pathogenic	criteria provided, multiple submitters, no conflicts
5316	NM_170784.3(MKKS):c.169A>G (p.Thr57Ala)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
549478	NM_170784.3(MKKS):c.119C>G (p.Ser40Ter)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
585168	NM_170784.3(MKKS):c.792T>G (p.Tyr264Ter)	MKKS	Pathogenic	criteria provided, single submitter
636041	NM_170784.3(MKKS):c.837del (p.Gly280fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
MKKS	Strong	Autosomal recessive	Bardet-Biedl syndrome 6	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MKKS	Orphanet:110	Bardet-Biedl syndrome
MKKS	Orphanet:2473	McKusick-Kaufman syndrome

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
MKKS	HGNC:7108	ENSG00000125863	Q9NPJ1	Molecular chaperone MKKS	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MKKS	Molecular chaperone MKKS	Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis.

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)
MKKS	Other/Unknown	no		Cpn60/GroEL/TCP-1, GroEL-like_apical_dom_sf, TCP-1-like_intermed_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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
endothelial cell	1
middle temporal gyrus	1
prefrontal cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MKKS	277	ubiquitous	marker	middle temporal gyrus, endothelial cell, prefrontal cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MKKS	2,728

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MKKS	Q9NPJ1	89.05

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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×	0.008	MKKS
Cargo trafficking to the periciliary membrane	1	248.3×	0.008	MKKS
Cilium Assembly	1	108.8×	0.012	MKKS
Organelle biogenesis and maintenance	1	66.0×	0.015	MKKS

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
pigment granule aggregation in cell center	1	8426.0×	0.002	MKKS
convergent extension involved in gastrulation	1	8426.0×	0.002	MKKS
negative regulation of appetite by leptin-mediated signaling pathway	1	4213.0×	0.002	MKKS
response to inositol	1	4213.0×	0.002	MKKS
artery smooth muscle contraction	1	1872.4×	0.003	MKKS
regulation of cilium beat frequency involved in ciliary motility	1	1872.4×	0.003	MKKS
gonad development	1	1123.5×	0.003	MKKS
striatum development	1	1123.5×	0.003	MKKS
regulation of stress fiber assembly	1	991.3×	0.003	MKKS
negative regulation of actin filament polymerization	1	936.2×	0.003	MKKS
detection of mechanical stimulus involved in sensory perception of sound	1	936.2×	0.003	MKKS
face development	1	802.5×	0.003	MKKS
melanosome transport	1	766.0×	0.003	MKKS
brain morphogenesis	1	732.7×	0.003	MKKS
chaperone-mediated protein complex assembly	1	702.2×	0.003	MKKS
developmental process	1	674.1×	0.003	MKKS
negative regulation of blood pressure	1	648.1×	0.003	MKKS
positive regulation of multicellular organism growth	1	495.6×	0.004	MKKS
vasodilation	1	366.4×	0.005	MKKS
photoreceptor cell maintenance	1	358.6×	0.005	MKKS
non-motile cilium assembly	1	290.6×	0.006	MKKS
social behavior	1	271.8×	0.006	MKKS
heart looping	1	267.5×	0.006	MKKS
determination of left/right symmetry	1	255.3×	0.006	MKKS
cartilage development	1	251.5×	0.006	MKKS
hippocampus development	1	230.8×	0.006	MKKS
cerebral cortex development	1	205.5×	0.006	MKKS
fat cell differentiation	1	181.2×	0.007	MKKS
sensory perception of smell	1	156.0×	0.008	MKKS
spermatid development	1	145.3×	0.008	MKKS

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
MKKS	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	MKKS

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)
MKKS	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.