Joubert syndrome 40

Summary

Joubert syndrome 40 (MONDO:0030462) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Joubert syndrome 40
Mondo ID	MONDO:0030462
OMIM	619582
UMLS	C5562007
MedGen	1794217
GARD	0025569
Is cancer (heuristic)	no

Also known as: JBTS40

Data availability: 12 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Joubert syndrome › Joubert syndrome 40

Related subtypes (38): Joubert syndrome 1, Joubert syndrome 10, Joubert syndrome 2, Joubert syndrome 3, Joubert syndrome with renal defect, Joubert syndrome 5, Joubert syndrome 6, Joubert syndrome 7, Joubert syndrome 9, Joubert syndrome 8, Joubert syndrome 13, Joubert syndrome 14, Joubert syndrome 15, Joubert syndrome 16, Joubert syndrome 17, Joubert syndrome 18, Joubert syndrome 20, Joubert syndrome 21, Joubert syndrome 22, Joubert syndrome 23, Joubert syndrome 24, Joubert syndrome 25, Joubert syndrome 26, Joubert syndrome 27, Joubert syndrome 28, Joubert syndrome 38, Joubert syndrome 39, Joubert syndrome 37, Joubert syndrome 35, Joubert syndrome 36, Joubert syndrome 30, Joubert syndrome 32, Joubert syndrome 31, Joubert syndrome 33, Joubert syndrome 19, Joubert syndrome 29, Joubert syndrome 11, Joubert syndrome 34

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

12 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 3 pathogenic/likely pathogenic, 3 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1300249	NM_025103.4(IFT74):c.535C>G (p.Gln179Glu)	IFT74	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1300250	NM_025103.4(IFT74):c.92del (p.Leu31fs)	IFT74	Pathogenic	no assertion criteria provided
1300251	NM_025103.4(IFT74):c.306-24A>G	IFT74	Pathogenic	no assertion criteria provided
1300253	NM_025103.4(IFT74):c.853G>T (p.Glu285Ter)	IFT74	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1686853	NM_025103.4(IFT74):c.975-2_975-1del	IFT74	Pathogenic	criteria provided, single submitter
1925311	NM_025103.4(IFT74):c.358G>T (p.Glu120Ter)	IFT74	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1300252	NM_025103.4(IFT74):c.85C>T (p.Arg29Ter)	IFT74	Likely pathogenic	criteria provided, single submitter
1401716	NM_025103.4(IFT74):c.902C>T (p.Pro301Leu)	IFT74	Uncertain significance	criteria provided, multiple submitters, no conflicts
1415312	NM_025103.4(IFT74):c.152G>A (p.Arg51His)	IFT74	Uncertain significance	criteria provided, multiple submitters, no conflicts
1928056	NM_025103.4(IFT74):c.587C>T (p.Ala196Val)	IFT74	Uncertain significance	criteria provided, multiple submitters, no conflicts
2170750	NM_025103.4(IFT74):c.1343G>A (p.Arg448His)	IFT74	Uncertain significance	criteria provided, multiple submitters, no conflicts
2184093	NM_025103.4(IFT74):c.1342C>T (p.Arg448Cys)	IFT74	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IFT74	Orphanet:110	Bardet-Biedl syndrome
IFT74	Orphanet:137893	Male infertility due to large-headed multiflagellar polyploid spermatozoa
IFT74	Orphanet:475	Isolated Joubert 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
IFT74	HGNC:21424	ENSG00000096872	Q96LB3	Intraflagellar transport protein 74 homolog	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IFT74	Intraflagellar transport protein 74 homolog	Component of the intraflagellar transport (IFT) complex B: together with IFT81, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium.

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)
IFT74	Other/Unknown	no		IFT74

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
bronchial epithelial cell	1
caput epididymis	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFT74	272	ubiquitous	marker	bronchial epithelial cell, caput epididymis, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFT74	1,937

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IFT74	Q96LB3	81.21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Intraflagellar transport	1	200.3×	0.005	IFT74

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
intraciliary transport involved in cilium assembly	1	2407.4×	0.003	IFT74
keratinocyte development	1	1532.0×	0.003	IFT74
positive regulation of cell adhesion mediated by integrin	1	1053.2×	0.003	IFT74
intraciliary anterograde transport	1	887.0×	0.003	IFT74
negative regulation of keratinocyte proliferation	1	702.2×	0.003	IFT74
keratinocyte proliferation	1	581.1×	0.003	IFT74
non-motile cilium assembly	1	290.6×	0.006	IFT74
determination of left/right symmetry	1	255.3×	0.006	IFT74
Notch signaling pathway	1	141.6×	0.009	IFT74
heart development	1	78.8×	0.015	IFT74
cilium assembly	1	73.6×	0.015	IFT74
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	IFT74

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
IFT74	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	IFT74

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)
IFT74	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.