Nephronophthisis 11

Summary

Nephronophthisis 11 (MONDO:0013302) is a disease caused by TMEM67 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: TMEM67 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 272

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephronophthisis 11
Mondo ID	MONDO:0013302
OMIM	613550
DOID	DOID:0111118
UMLS	C3150796
MedGen	462146
GARD	0018080
Is cancer (heuristic)	no

Also known as: nephronophthisis 11 · nephronophthisis type 11 · NPHP11

Data availability: 272 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › nephronophthisis › nephronophthisis 11

Related subtypes (17): nephronophthisis 1, nephronophthisis 2, nephronophthisis 3, nephronophthisis 4, nephronophthisis 7, nephronophthisis-like nephropathy 1, nephronophthisis 12, nephronophthisis 9, nephronophthisis 13, nephronophthisis 14, nephronophthisis 15, nephronophthisis 16, nephronophthisis 18, nephronophthisis 19, nephronophthisis 20, late-onset nephronophthisis, nephronophthisis-like nephropathy 2

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

272 retrieved; paginated sample, class counts are floors:

142 uncertain significance, 40 conflicting classifications of pathogenicity, 29 pathogenic/likely pathogenic, 17 likely benign, 17 likely pathogenic, 14 pathogenic, 10 benign/likely benign, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1072098	NM_153704.6(TMEM67):c.1975C>T (p.Arg659Ter)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074275	NM_153704.6(TMEM67):c.1338_1350del (p.Ala447fs)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126306	NM_153704.6(TMEM67):c.748G>A (p.Gly250Arg)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1371	NM_153704.6(TMEM67):c.1538A>G (p.Tyr513Cys)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1376	NM_153704.6(TMEM67):c.622A>T (p.Arg208Ter)	TMEM67	Pathogenic	criteria provided, multiple submitters, no conflicts
1378	NM_153704.6(TMEM67):c.2498T>C (p.Ile833Thr)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1380	NM_153704.6(TMEM67):c.312+5G>A	TMEM67	Pathogenic	criteria provided, multiple submitters, no conflicts
1381	NM_153704.6(TMEM67):c.1769T>C (p.Phe590Ser)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1382	NM_153704.6(TMEM67):c.2461G>A (p.Gly821Ser)	TMEM67	Pathogenic	criteria provided, single submitter
1383	NM_153704.6(TMEM67):c.1843T>C (p.Cys615Arg)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1384	NM_153704.6(TMEM67):c.869G>T (p.Trp290Leu)	TMEM67	Pathogenic	no assertion criteria provided
1385	NM_153704.6(TMEM67):c.2461G>C (p.Gly821Arg)	TMEM67	Pathogenic	no assertion criteria provided
1387	NM_153704.6(TMEM67):c.755T>C (p.Met252Thr)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1411457	NM_153704.6(TMEM67):c.1387C>T (p.Arg463Ter)	TMEM67	Pathogenic	criteria provided, multiple submitters, no conflicts
1454299	NM_153704.6(TMEM67):c.1927C>T (p.Arg643Ter)	TMEM67	Pathogenic	criteria provided, multiple submitters, no conflicts
1691287	NM_153704.6(TMEM67):c.479_480del (p.Phe160fs)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
191259	NM_153704.6(TMEM67):c.1413-2A>G	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
216826	NM_153704.6(TMEM67):c.725A>G (p.Asn242Ser)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217710	NM_153704.6(TMEM67):c.769A>G (p.Met257Val)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217712	NM_153704.6(TMEM67):c.300C>A (p.Cys100Ter)	TMEM67	Pathogenic	criteria provided, multiple submitters, no conflicts
217717	NM_153704.6(TMEM67):c.2290C>T (p.Arg764Ter)	TMEM67	Pathogenic	criteria provided, multiple submitters, no conflicts
217724	NM_153704.6(TMEM67):c.1351C>T (p.Arg451Ter)	TMEM67	Pathogenic	criteria provided, multiple submitters, no conflicts
217726	NM_153704.6(TMEM67):c.1115C>A (p.Thr372Lys)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2178475	NM_153704.6(TMEM67):c.2521C>T (p.Gln841Ter)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
219997	NM_153704.6(TMEM67):c.517T>C (p.Cys173Arg)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
225493	NM_153704.6(TMEM67):c.1353del (p.Glu452fs)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2431214	NM_153704.6(TMEM67):c.2758del (p.Tyr920fs)	TMEM67	Pathogenic	criteria provided, multiple submitters, no conflicts
2431230	NM_153704.6(TMEM67):c.329A>G (p.Asp110Gly)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2691706	NM_153704.6(TMEM67):c.2429_2433del (p.Lys810fs)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
282355	NM_153704.6(TMEM67):c.863C>A (p.Ser288Ter)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 5 · 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
TMEM67	Definitive	Autosomal recessive	nephronophthisis 11	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TMEM67	HGNC:28396	ENSG00000164953	Q5HYA8	Meckelin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TMEM67	Meckelin	Required for ciliary structure and function.

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)
TMEM67	Other/Unknown	no		Growth_fac_rcpt_cys_sf, Meckelin

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
buccal mucosa cell	1
calcaneal tendon	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TMEM67	203	ubiquitous	marker	buccal mucosa cell, right uterine tube, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TMEM67	1,194

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TMEM67	Q5HYA8	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Anchoring of the basal body to the plasma membrane	1	113.1×	0.014	TMEM67
Cilium Assembly	1	108.8×	0.014	TMEM67
Organelle biogenesis and maintenance	1	66.0×	0.015	TMEM67

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
negative regulation of centrosome duplication	1	3370.4×	0.001	TMEM67
non-canonical Wnt signaling pathway	1	581.1×	0.003	TMEM67
ERAD pathway	1	181.2×	0.007	TMEM67
cilium assembly	1	73.6×	0.014	TMEM67

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
TMEM67	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	TMEM67

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)
TMEM67	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.