Primary ciliary dyskinesia 26

Summary

Primary ciliary dyskinesia 26 (MONDO:0014211) is a disease caused by CFAP298 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: CFAP298 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 26
Mondo ID	MONDO:0014211
OMIM	615500
DOID	DOID:0110627
UMLS	C3809684
MedGen	816014
GARD	0015974
Is cancer (heuristic)	no

Also known as: CFAP298 primary ciliary dyskinesia · CILD26 · ciliary dyskinesia, primary, 26 · ciliary dyskinesia, primary, type 26 · primary ciliary dyskinesia caused by mutation in CFAP298 · primary ciliary dyskinesia type 26

Data availability: 12 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › primary ciliary dyskinesia › primary ciliary dyskinesia 26

Related subtypes (58): ciliary discoordination due to random ciliary orientation, ciliary dyskinesia with transposition of ciliary microtubules, ciliary dyskinesia with defective radial spokes, ciliary dyskinesia with excessively long cilia, Stromme syndrome, primary ciliary dyskinesia 1, ciliary dyskinesia, primary, 36, X-linked, primary ciliary dyskinesia 2, primary ciliary dyskinesia 3, primary ciliary dyskinesia 4, primary ciliary dyskinesia 5, primary ciliary dyskinesia 6, primary ciliary dyskinesia 7, primary ciliary dyskinesia 8, primary ciliary dyskinesia 9, primary ciliary dyskinesia 10, primary ciliary dyskinesia 11, primary ciliary dyskinesia 12, primary ciliary dyskinesia 13, primary ciliary dyskinesia 14, primary ciliary dyskinesia 15, primary ciliary dyskinesia 16, primary ciliary dyskinesia 17, primary ciliary dyskinesia 18, primary ciliary dyskinesia 19, primary ciliary dyskinesia 20, primary ciliary dyskinesia 21, primary ciliary dyskinesia 22, primary ciliary dyskinesia 23, primary ciliary dyskinesia 24, primary ciliary dyskinesia 25, primary ciliary dyskinesia 27, primary ciliary dyskinesia 28, primary ciliary dyskinesia 29, primary ciliary dyskinesia 30, primary ciliary dyskinesia 32, primary ciliary dyskinesia 33, primary ciliary dyskinesia 34, primary ciliary dyskinesia 35, ciliary dyskinesia, primary, 46, ciliary dyskinesia, primary, 47, and lissencephaly, ciliary dyskinesia, primary, 48, without situs inversus, ciliary dyskinesia, primary, 39, ciliary dyskinesia, primary, 40, ciliary dyskinesia, primary, 41, ciliary dyskinesia, primary, 42, ciliary dyskinesia, primary, 43, ciliary dyskinesia, primary, 44, ciliary dyskinesia, primary, 45, ciliary dyskinesia, primary, 37, ciliary dyskinesia, primary, 38, ciliary dyskinesia, primary, 54, ciliary dyskinesia, primary, 49, without situs inversus, ciliary dyskinesia, primary, 50, ciliary dyskinesia, primary, 51, ciliary dyskinesia, primary, 52, ciliary dyskinesia, primary, 53, CFAP46-related primary ciliary dyskinesia

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:

4 pathogenic, 3 uncertain significance, 2 pathogenic/likely pathogenic, 1 benign, 1 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2071804	NM_021254.4(CFAP298):c.673C>T (p.Gln225Ter)	CFAP298	Pathogenic	criteria provided, multiple submitters, no conflicts
525239	NM_021254.4(CFAP298):c.557_566dup (p.Gln190fs)	CFAP298	Pathogenic	criteria provided, multiple submitters, no conflicts
869379	NM_021254.4(CFAP298):c.721C>T (p.Gln241Ter)	CFAP298	Pathogenic	criteria provided, single submitter
88689	NM_021254.4(CFAP298):c.292C>T (p.Arg98Ter)	CFAP298	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
88690	NM_021254.4(CFAP298):c.792_795del (p.Ala263_Tyr264insTer)	CFAP298	Pathogenic	no assertion criteria provided
209002	NM_021254.4(CFAP298):c.735C>G (p.Tyr245Ter)	CFAP298-TCP10L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1025340	NM_021254.4(CFAP298):c.829del (p.Arg277fs)	CFAP298	Uncertain significance	criteria provided, multiple submitters, no conflicts
525246	NM_021254.4(CFAP298):c.422A>G (p.Asp141Gly)	CFAP298	Uncertain significance	criteria provided, multiple submitters, no conflicts
1299358	NM_021254.4(CFAP298):c.160C>T (p.His54Tyr)	CFAP298-TCP10L	Uncertain significance	criteria provided, single submitter
1550691	NM_021254.4(CFAP298):c.308-16C>G	CFAP298	Benign	criteria provided, multiple submitters, no conflicts
241378	NM_021254.4(CFAP298):c.622G>A (p.Val208Met)	CFAP298	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
697710	NM_021254.4(CFAP298):c.552T>A (p.Ile184=)	CFAP298	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
CFAP298	Strong	Autosomal recessive	primary ciliary dyskinesia 26	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CFAP298	Orphanet:244	Primary ciliary dyskinesia

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CFAP298	HGNC:1301	ENSG00000159079	P57076	Cilia- and flagella-associated protein 298	gencc,clinvar
CFAP298-TCP10L	HGNC:54636	ENSG00000265590		CFAP298-TCP10L readthrough	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CFAP298	Cilia- and flagella-associated protein 298	Plays a role in motile cilium function, possibly by acting on outer dynein arm assembly.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CFAP298	Other/Unknown	no		CFAP298
CFAP298-TCP10L	Other/Unknown	no

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
left testis	2
olfactory segment of nasal mucosa	1
right uterine tube	1
calcaneal tendon	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CFAP298	173	ubiquitous	marker	right uterine tube, olfactory segment of nasal mucosa, left testis
CFAP298-TCP10L	134	ubiquitous	marker	calcaneal tendon, left testis, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFAP298	596
CFAP298-TCP10L	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CFAP298	P57076	86.54

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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
regulation of cilium movement	1	4213.0×	5e-04	CFAP298
cilium assembly	1	73.6×	0.014	CFAP298

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
CFAP298	0	0
CFAP298-TCP10L	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	2	CFAP298, CFAP298-TCP10L

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)
CFAP298	0	—
CFAP298-TCP10L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.