Joubert syndrome 16

Summary

Joubert syndrome 16 (MONDO:0013764) is a disease caused by TMEM138 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TMEM138 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 160

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Joubert syndrome 16
Mondo ID	MONDO:0013764
OMIM	614465
DOID	DOID:0110985
UMLS	C3280906
MedGen	482536
GARD	0015807
Is cancer (heuristic)	no

Also known as: JBTS16 · Joubert syndrome 16 · Joubert syndrome caused by mutation in TMEM138 · Joubert syndrome type 16 · TMEM138 Joubert syndrome

Data availability: 160 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Joubert syndrome with oculorenal defect › Joubert syndrome 16

Related subtypes (4): Joubert syndrome 2, Joubert syndrome 5, Joubert syndrome 9, Joubert syndrome 14

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

160 retrieved; paginated sample, class counts are floors:

83 uncertain significance, 45 likely benign, 10 conflicting classifications of pathogenicity, 8 pathogenic, 6 pathogenic/likely pathogenic, 4 likely pathogenic, 3 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1424816	NM_016464.5(TMEM138):c.83del (p.Phe27_Ser28insTer)	TMEM138	Pathogenic	criteria provided, single submitter
1458178	NM_016464.5(TMEM138):c.94C>T (p.Gln32Ter)	TMEM138	Pathogenic	criteria provided, single submitter
1460234	NC_000011.9:g.(?61133497)(61133708_?)del	TMEM138	Pathogenic	criteria provided, single submitter
1505578	NM_016464.5(TMEM138):c.306_307dup (p.Arg103fs)	TMEM138	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1982443	NM_016464.5(TMEM138):c.311G>A (p.Trp104Ter)	TMEM138	Pathogenic	criteria provided, single submitter
2018227	NM_016464.5(TMEM138):c.306dup (p.Arg103fs)	TMEM138	Pathogenic	criteria provided, single submitter
2046391	NM_016464.5(TMEM138):c.307del (p.Arg103fs)	TMEM138	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31187	NM_016464.5(TMEM138):c.128+5G>A	TMEM138	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31188	NM_016464.5(TMEM138):c.287A>G (p.His96Arg)	TMEM138	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31189	NM_016464.5(TMEM138):c.380C>T (p.Ala127Val)	TMEM138	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31190	NM_016464.5(TMEM138):c.376G>A (p.Ala126Thr)	TMEM138	Pathogenic	no assertion criteria provided
3599796	NM_016464.5(TMEM138):c.37_38del (p.Leu13fs)	TMEM138	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3686760	NM_016464.5(TMEM138):c.293G>A (p.Trp98Ter)	TMEM138	Pathogenic	criteria provided, single submitter
917959	NM_016464.5(TMEM138):c.377-3C>G	TMEM138	Pathogenic	no assertion criteria provided
3599797	NM_016464.5(TMEM138):c.37del (p.Leu13fs)	TMEM138	Likely pathogenic	criteria provided, single submitter
3599801	NM_016464.5(TMEM138):c.128+2T>G	TMEM138	Likely pathogenic	criteria provided, single submitter
3691403	NM_016464.5(TMEM138):c.300+1G>T	TMEM138	Likely pathogenic	criteria provided, single submitter
4278416	NM_016464.5(TMEM138):c.97_98del (p.Lys33fs)	TMEM138	Likely pathogenic	criteria provided, single submitter
1102738	NM_016464.5(TMEM138):c.81C>T (p.Phe27=)	TMEM138	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1644414	NM_016464.5(TMEM138):c.231G>A (p.Lys77=)	TMEM138	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
260747	NM_016464.5(TMEM138):c.216C>T (p.Asn72=)	TMEM138	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305063	NM_016464.5(TMEM138):c.327C>T (p.Ser109=)	TMEM138	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305066	NM_016464.5(TMEM138):c.420A>G (p.Arg140=)	TMEM138	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305067	NM_016464.5(TMEM138):c.482G>A (p.Arg161Gln)	TMEM138	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
31191	NM_016464.5(TMEM138):c.389A>G (p.Tyr130Cys)	TMEM138	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
437008	NM_016464.5(TMEM138):c.74A>G (p.Asn25Ser)	TMEM138	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
570566	NM_016464.5(TMEM138):c.461G>A (p.Arg154His)	TMEM138	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
837999	NM_016464.5(TMEM138):c.415G>A (p.Val139Ile)	TMEM138	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1204836	NM_016464.5(TMEM138):c.128+3G>T	TMEM138	Uncertain significance	criteria provided, multiple submitters, no conflicts
1343681	NM_016464.5(TMEM138):c.415G>T (p.Val139Leu)	TMEM138	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
TMEM138	Strong	Autosomal recessive	Joubert syndrome 16	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TMEM138	Orphanet:2318	Joubert syndrome with oculorenal defect

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
TMEM138	HGNC:26944	ENSG00000149483	Q9NPI0	Transmembrane protein 138	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TMEM138	Transmembrane protein 138	Required for ciliogenesis.

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)
TMEM138	Other/Unknown	no		TM_138

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
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TMEM138	245	ubiquitous	marker	right adrenal gland, right adrenal gland cortex, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TMEM138	469

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TMEM138	Q9NPI0	86.42

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
cilium assembly	1	73.6×	0.014	TMEM138

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
TMEM138	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	TMEM138

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)
TMEM138	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.