Joubert syndrome 26

Summary

Joubert syndrome 26 (MONDO:0014771) is a disease caused by KATNIP (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: KATNIP (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 31

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Joubert syndrome 26
Mondo ID	MONDO:0014771
OMIM	616784
DOID	DOID:0110995
UMLS	C4084843
MedGen	900415
GARD	0016160
Is cancer (heuristic)	no

Also known as: JBTS26 · Joubert syndrome 26 · Joubert syndrome caused by mutation in KIAA0556 · Joubert syndrome type 26 · KIAA0556 Joubert syndrome

Data availability: 31 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Joubert syndrome › Joubert syndrome 26

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 27, Joubert syndrome 28, Joubert syndrome 38, Joubert syndrome 39, Joubert syndrome 40, 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

31 retrieved; paginated sample, class counts are floors:

13 likely pathogenic, 8 uncertain significance, 5 pathogenic, 2 conflicting classifications of pathogenicity, 2 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1690878	NM_015202.5(KATNIP):c.27dup (p.Glu10fs)	KATNIP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3233461	NC_000016.9:g.(27561499_27585221)_(27585278_27629745)del	KATNIP	Pathogenic	criteria provided, single submitter
3251831	NM_015202.5(KATNIP):c.19C>T (p.Arg7Ter)	KATNIP	Pathogenic	criteria provided, multiple submitters, no conflicts
3895621	NM_015202.5(KATNIP):c.3584del (p.Pro1195fs)	KATNIP	Pathogenic	criteria provided, single submitter
4847907	NM_015202.5(KATNIP):c.319C>T (p.Arg107Ter)	KATNIP	Pathogenic	criteria provided, single submitter
489396	NM_015202.5(KATNIP):c.4420del (p.Met1474fs)	KATNIP	Pathogenic	no assertion criteria provided
1327056	NM_015202.5(KATNIP):c.2959del (p.Asp987fs)	KATNIP	Likely pathogenic	no assertion criteria provided
1334634	NM_015202.5(KATNIP):c.4133+1G>A	KATNIP	Likely pathogenic	criteria provided, single submitter
218948	NM_015202.5(KATNIP):c.2674C>T (p.Gln892Ter)	KATNIP	Likely pathogenic	criteria provided, single submitter
2431062	NM_015202.5(KATNIP):c.274_275del (p.Phe92fs)	KATNIP	Likely pathogenic	criteria provided, single submitter
2501211	NM_015202.5(KATNIP):c.922C>T (p.Gln308Ter)	KATNIP	Likely pathogenic	criteria provided, single submitter
2690629	NM_015202.5(KATNIP):c.3632-1G>C	KATNIP	Likely pathogenic	criteria provided, single submitter
3242074	NM_015202.5(KATNIP):c.654_655insA (p.Asp219fs)	KATNIP	Likely pathogenic	criteria provided, single submitter
3362825	NM_015202.5(KATNIP):c.4394_4395del (p.Val1465fs)	KATNIP	Likely pathogenic	criteria provided, single submitter
3897822	NM_015202.5(KATNIP):c.3973G>A (p.Gly1325Arg)	KATNIP	Likely pathogenic	criteria provided, single submitter
4081470	NM_015202.5(KATNIP):c.808+2T>C	KATNIP	Likely pathogenic	criteria provided, single submitter
4292626	NM_015202.5(KATNIP):c.3976-2A>G	KATNIP	Likely pathogenic	criteria provided, single submitter
4683121	NM_015202.5(KATNIP):c.3384del (p.Asp1129fs)	KATNIP	Likely pathogenic	criteria provided, single submitter
917945	NM_015202.5(KATNIP):c.1672C>T (p.Arg558Ter)	KATNIP	Likely pathogenic	no assertion criteria provided
1342577	NM_015202.5(KATNIP):c.2849C>T (p.Ser950Leu)	KATNIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
828110	NM_015202.5(KATNIP):c.49C>T (p.Arg17Ter)	KATNIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1098660	NM_015202.5(KATNIP):c.2722C>T (p.Arg908Cys)	KATNIP	Uncertain significance	criteria provided, multiple submitters, no conflicts
1342576	NM_015202.5(KATNIP):c.700A>G (p.Ser234Gly)	KATNIP	Uncertain significance	criteria provided, single submitter
1924451	NM_015202.5(KATNIP):c.4019C>T (p.Pro1340Leu)	KATNIP	Uncertain significance	criteria provided, single submitter
1945341	NM_015202.5(KATNIP):c.4399G>A (p.Asp1467Asn)	KATNIP	Uncertain significance	criteria provided, multiple submitters, no conflicts
2191562	NM_015202.5(KATNIP):c.4850G>A (p.Arg1617His)	KATNIP	Uncertain significance	criteria provided, multiple submitters, no conflicts
2442073	NM_015202.5(KATNIP):c.3239A>G (p.Lys1080Arg)	KATNIP	Uncertain significance	criteria provided, single submitter
3065702	NM_015202.5(KATNIP):c.3151C>A (p.Pro1051Thr)	KATNIP	Uncertain significance	criteria provided, single submitter
828109	NM_015202.5(KATNIP):c.4711A>G (p.Ser1571Gly)	KATNIP	Uncertain significance	criteria provided, multiple submitters, no conflicts
771762	NM_015202.5(KATNIP):c.3913G>A (p.Glu1305Lys)	KATNIP	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
KATNIP	Strong	Autosomal recessive	Joubert syndrome 26	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KATNIP	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
KATNIP	HGNC:29068	ENSG00000047578	O60303	Katanin-interacting protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KATNIP	Katanin-interacting protein	May influence the stability of microtubules (MT), possibly through interaction with the MT-severing katanin complex.

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)
KATNIP	Other/Unknown	no		KATNIP, KATNIP_dom

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
epithelium of bronchus	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KATNIP	251	ubiquitous	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KATNIP	1,162

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KATNIP	O60303	58.93

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
negative regulation of motile cilium assembly	1	5617.3×	4e-04	KATNIP
cerebrospinal fluid circulation	1	887.0×	0.001	KATNIP

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
KATNIP	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	KATNIP

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)
KATNIP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.