Meckel syndrome, type 9

Summary

Meckel syndrome, type 9 (MONDO:0013630) is a disease caused by B9D1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: B9D1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 27

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Meckel syndrome, type 9
Mondo ID	MONDO:0013630
OMIM	614209
UMLS	C3280155
MedGen	481785
GARD	0015773
Is cancer (heuristic)	no

Also known as: B9D1 Meckel syndrome · meckel syndrome 9 · Meckel syndrome caused by mutation in B9D1 · Meckel syndrome, type 9 · MKS9

Data availability: 27 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Meckel syndrome › Meckel syndrome, type 9

Related subtypes (13): Meckel syndrome, type 1, NPHP3-related Meckel-like syndrome, Meckel syndrome, type 2, Meckel syndrome, type 3, Meckel syndrome, type 4, Meckel syndrome, type 5, Meckel syndrome, type 6, Meckel syndrome, type 8, Meckel syndrome, type 10, Meckel syndrome, type 11, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, meckel syndrome 14, Meckel syndrome 13

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

27 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 6 conflicting classifications of pathogenicity, 5 benign, 2 benign/likely benign, 1 likely pathogenic, 1 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
31102	NM_015681.6(B9D1):c.341+2T>C	B9D1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31103	NC_000017.11:g.(?18856298)(20402192_?)del	LOC130060474	Pathogenic	no assertion criteria provided
1687049	NM_015681.6(B9D1):c.529G>C (p.Asp177His)	B9D1	Likely pathogenic	criteria provided, single submitter
217555	NM_015681.6(B9D1):c.95A>G (p.Tyr32Cys)	B9D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
260674	NM_015681.6(B9D1):c.376T>A (p.Ser126Thr)	B9D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
388102	NM_015681.6(B9D1):c.597C>G (p.Pro199=)	B9D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
695508	NM_015681.6(B9D1):c.516C>T (p.Asn172=)	B9D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
889437	NM_015681.6(B9D1):c.568A>T (p.Thr190Ser)	B9D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
890120	NM_015681.6(B9D1):c.9C>G (p.Thr3=)	B9D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2073172	NM_015681.6(B9D1):c.505CTC[1] (p.Leu170del)	B9D1	Uncertain significance	criteria provided, multiple submitters, no conflicts
266100	NM_015681.6(B9D1):c.209T>C (p.Ile70Thr)	B9D1	Uncertain significance	criteria provided, single submitter
322197	NM_015681.6(B9D1):c.*47C>T	B9D1	Uncertain significance	criteria provided, single submitter
322198	NM_015681.6(B9D1):c.457G>A (p.Gly153Ser)	B9D1	Uncertain significance	criteria provided, single submitter
322199	NM_015681.6(B9D1):c.90C>T (p.Cys30=)	B9D1	Uncertain significance	criteria provided, multiple submitters, no conflicts
322201	NM_015681.6(B9D1):c.-79C>G	B9D1	Uncertain significance	criteria provided, single submitter
889436	NM_015681.6(B9D1):c.*58G>A	B9D1	Uncertain significance	criteria provided, single submitter
890121	NM_015681.6(B9D1):c.-21C>T	B9D1	Uncertain significance	criteria provided, single submitter
890122	NM_015681.6(B9D1):c.-42C>T	B9D1	Uncertain significance	criteria provided, single submitter
983354	NM_001321219.2(B9D1):c.425C>A (p.Ser142Ter)	B9D1	Uncertain significance	criteria provided, single submitter
4278455	NM_138364.4(PRMT9):c.473A>G (p.Asn158Ser)	PRMT9	Uncertain significance	criteria provided, single submitter
1192493	NM_001321218.2(B9D1):c.*61C>T	B9D1	Benign	criteria provided, multiple submitters, no conflicts
260671	NM_015681.6(B9D1):c.181C>T (p.Arg61Trp)	B9D1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
260675	NM_015681.6(B9D1):c.472+28C>T	B9D1	Benign	criteria provided, multiple submitters, no conflicts
260676	NM_015681.6(B9D1):c.580T>C (p.Leu194=)	B9D1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
322200	NM_015681.6(B9D1):c.-70G>A	B9D1	Benign	criteria provided, multiple submitters, no conflicts
322202	NM_015681.6(B9D1):c.-110G>A	B9D1	Benign	criteria provided, multiple submitters, no conflicts
674719	NM_015681.6(B9D1):c.63+23G>A	LOC130060455	Benign	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
B9D1	Strong	Autosomal recessive	Meckel syndrome, type 9	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
B9D1	Orphanet:475	Isolated Joubert syndrome
B9D1	Orphanet:564	Meckel syndrome

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
B9D1	HGNC:24123	ENSG00000108641	Q9UPM9	B9 domain-containing protein 1	gencc,clinvar
PRMT9	HGNC:25099	ENSG00000164169	Q6P2P2	Protein arginine N-methyltransferase 9	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
B9D1	B9 domain-containing protein 1	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
PRMT9	Protein arginine N-methyltransferase 9	Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA).

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
B9D1	Other/Unknown	no		C2_B9-type_dom
PRMT9	Enzyme (other)	yes	2.1.1.320	TPR-like_helical_dom_sf, TPR_rpt, Arg_MeTrfase

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	1
left testis	1
right uterine tube	1
left ovary	1
primordial germ cell in gonad	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
B9D1	224	ubiquitous	marker	right uterine tube, adenohypophysis, left testis
PRMT9	243	ubiquitous	marker	secondary oocyte, primordial germ cell in gonad, left ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRMT9	1,952
B9D1	765

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRMT9	Q6P2P2	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
B9D1	Q9UPM9	83.05

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 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
Anchoring of the basal body to the plasma membrane	1	113.1×	0.014	B9D1
Cilium Assembly	1	108.8×	0.014	B9D1
Organelle biogenesis and maintenance	1	66.0×	0.015	B9D1

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
neuroepithelial cell differentiation	1	766.0×	0.011	B9D1
vasculature development	1	561.7×	0.011	B9D1
camera-type eye development	1	179.3×	0.020	B9D1
embryonic digit morphogenesis	1	150.5×	0.020	B9D1
regulation of protein localization	1	102.8×	0.020	B9D1
smoothened signaling pathway	1	90.6×	0.020	B9D1
methylation	1	85.1×	0.020	PRMT9
mRNA processing	1	39.4×	0.030	PRMT9
cilium assembly	1	36.8×	0.030	B9D1
chromatin remodeling	1	36.5×	0.030	PRMT9
in utero embryonic development	1	36.0×	0.030	B9D1
regulation of DNA-templated transcription	1	15.8×	0.062	PRMT9

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
B9D1	0	0
PRMT9	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PRMT9	40	Binding:40

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PRMT9	2.1.1.320	type II protein arginine methyltransferase

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	PRMT9
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	B9D1

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)
B9D1	0	—
PRMT9	40	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.