Primary ciliary dyskinesia 18

Summary

Primary ciliary dyskinesia 18 (MONDO:0013940) is a disease caused by DNAAF5 (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: DNAAF5 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 64

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 18
Mondo ID	MONDO:0013940
OMIM	614874
DOID	DOID:0110604
UMLS	C3543825
MedGen	762331
GARD	0015868
Is cancer (heuristic)	no

Also known as: CILD18 · ciliary dyskinesia, primary, 18 · ciliary dyskinesia, primary, type 18 · DNAAF5 primary ciliary dyskinesia · primary ciliary dyskinesia caused by mutation in DNAAF5 · primary ciliary dyskinesia type 18

Data availability: 64 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › primary ciliary dyskinesia › primary ciliary dyskinesia 18

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 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 26, 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

64 retrieved; paginated sample, class counts are floors:

20 uncertain significance, 16 benign, 7 benign/likely benign, 6 conflicting classifications of pathogenicity, 6 pathogenic/likely pathogenic, 5 likely benign, 2 likely pathogenic, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1914650	NM_017802.4(DNAAF5):c.757C>T (p.Arg253Ter)	DNAAF5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2635405	NM_017802.4(DNAAF5):c.2450del (p.Ser817fs)	DNAAF5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39684	NM_017802.4(DNAAF5):c.2384T>C (p.Leu795Pro)	DNAAF5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
410302	NM_017802.4(DNAAF5):c.1499G>T (p.Cys500Phe)	DNAAF5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4278018	NM_017802.4(DNAAF5):c.1988_2030dup (p.Ser679fs)	DNAAF5	Pathogenic	criteria provided, single submitter
454858	NM_017802.4(DNAAF5):c.2108_2114delinsCCACCCTGGGT (p.Met703fs)	DNAAF5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
651485	NM_017802.4(DNAAF5):c.926G>A (p.Trp309Ter)	DNAAF5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
689528	NM_017802.4(DNAAF5):c.55dup (p.Ala19fs)	DNAAF5	Pathogenic	no assertion criteria provided
3242170	NM_017802.4(DNAAF5):c.991_992insGG (p.Ala331fs)	DNAAF5	Likely pathogenic	criteria provided, single submitter
573238	NM_017802.4(DNAAF5):c.1470+1G>A	DNAAF5	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1447086	NM_017802.4(DNAAF5):c.1027C>T (p.Arg343Cys)	DNAAF5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
410295	NM_017802.4(DNAAF5):c.2024C>T (p.Thr675Met)	DNAAF5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
410306	NM_017802.4(DNAAF5):c.1487G>A (p.Arg496His)	DNAAF5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
454869	NM_017802.4(DNAAF5):c.788G>A (p.Arg263Gln)	DNAAF5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
525340	NM_017802.4(DNAAF5):c.781G>A (p.Val261Ile)	DNAAF5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241208	NM_017802.4(DNAAF5):c.550C>A (p.Arg184Ser)	PRKAR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1040343	NM_017802.4(DNAAF5):c.2251C>T (p.Arg751Cys)	DNAAF5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1390155	NM_017802.4(DNAAF5):c.1246G>A (p.Val416Met)	DNAAF5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1415748	NM_017802.4(DNAAF5):c.1714G>A (p.Ala572Thr)	DNAAF5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1500969	NM_017802.4(DNAAF5):c.2510C>T (p.Ser837Leu)	DNAAF5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1698879	NM_017802.4(DNAAF5):c.889G>A (p.Glu297Lys)	DNAAF5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1787401	NM_017802.4(DNAAF5):c.218G>C (p.Trp73Ser)	DNAAF5	Uncertain significance	criteria provided, multiple submitters, no conflicts
2440896	NM_017802.4(DNAAF5):c.2201del (p.Gly734fs)	DNAAF5	Uncertain significance	criteria provided, single submitter
2440897	NM_017802.4(DNAAF5):c.1234G>A (p.Glu412Lys)	DNAAF5	Uncertain significance	criteria provided, multiple submitters, no conflicts
3594914	NM_017802.4(DNAAF5):c.1410G>C (p.Pro470=)	DNAAF5	Uncertain significance	criteria provided, single submitter
454847	NM_017802.4(DNAAF5):c.1208G>A (p.Arg403Gln)	DNAAF5	Uncertain significance	criteria provided, multiple submitters, no conflicts
454857	NM_017802.4(DNAAF5):c.1997C>T (p.Ala666Val)	DNAAF5	Uncertain significance	criteria provided, multiple submitters, no conflicts
4685832	NM_017802.4(DNAAF5):c.2272G>A (p.Asp758Asn)	DNAAF5	Uncertain significance	criteria provided, single submitter
525212	NM_017802.4(DNAAF5):c.1715C>T (p.Ala572Val)	DNAAF5	Uncertain significance	criteria provided, multiple submitters, no conflicts
525305	NM_017802.4(DNAAF5):c.1856C>T (p.Pro619Leu)	DNAAF5	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 3 · 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
DNAAF5	Strong	Autosomal recessive	primary ciliary dyskinesia 18	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNAAF5	Orphanet:244	Primary ciliary dyskinesia
PRKAR1B	Orphanet:412066	PRKAR1B-related neurodegenerative dementia with intermediate filaments
PRKAR1B	Orphanet:692173	Marbach-Schaaf neurodevelopmental syndrome

Cohort genes → proteins

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DNAAF5	HGNC:26013	ENSG00000164818	Q86Y56	Dynein axonemal assembly factor 5	gencc,clinvar
CPLX1-AS1	HGNC:58706	ENSG00000289983		CPLX1 antisense RNA 1	clinvar
PRKAR1B	HGNC:9390	ENSG00000188191	P31321	cAMP-dependent protein kinase type I-beta regulatory subunit	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNAAF5	Dynein axonemal assembly factor 5	Cytoplasmic protein involved in the delivery of the dynein machinery to the motile cilium.
PRKAR1B	cAMP-dependent protein kinase type I-beta regulatory subunit	Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNAAF5	Other/Unknown	no		HEAT, ARM-like, ARM-type_fold
CPLX1-AS1	Other/Unknown	no
PRKAR1B	Other/Unknown	no		cNMP-bd_dom, cAMP_dep_PK_reg_su_I/II_a/b, cAMP_dep_PK_reg_su

Expression context

Cohort genes with no expression data: 1.

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	1

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
epithelium of bronchus	1
secondary oocyte	1
Brodmann (1909) area 10	1
cingulate cortex	1
right frontal lobe	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNAAF5	280	ubiquitous	marker	bronchial epithelial cell, secondary oocyte, epithelium of bronchus
CPLX1-AS1
PRKAR1B	243	ubiquitous	marker	Brodmann (1909) area 10, right frontal lobe, cingulate cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRKAR1B	2,865
DNAAF5	996
CPLX1-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRKAR1B	P31321	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DNAAF5	Q86Y56	92.80

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 48. Enrichment computed across 3 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
CREB1 phosphorylation through the activation of Adenylate Cyclase	1	878.5×	0.008	PRKAR1B
PKA activation in glucagon signalling	1	671.8×	0.008	PRKAR1B
PKA activation	1	634.4×	0.008	PRKAR1B
PKA-mediated phosphorylation of CREB	1	571.0×	0.008	PRKAR1B
DARPP-32 events	1	475.8×	0.008	PRKAR1B
Anti-inflammatory response favouring Leishmania parasite infection	1	393.8×	0.008	PRKAR1B
Leishmania parasite growth and survival	1	393.8×	0.008	PRKAR1B
Calmodulin induced events	1	380.7×	0.008	PRKAR1B
CaM pathway	1	380.7×	0.008	PRKAR1B
Ca-dependent events	1	368.4×	0.008	PRKAR1B
Aquaporin-mediated transport	1	368.4×	0.008	PRKAR1B
Glucagon signaling in metabolic regulation	1	346.1×	0.008	PRKAR1B
G-protein mediated events	1	326.3×	0.008	PRKAR1B
DAG and IP3 signaling	1	317.2×	0.008	PRKAR1B
Response of endothelial cells to shear stress	1	300.5×	0.008	PRKAR1B
FCGR3A-mediated IL10 synthesis	1	292.8×	0.008	PRKAR1B
Opioid Signalling	1	265.6×	0.008	PRKAR1B
PLC beta mediated events	1	265.6×	0.008	PRKAR1B
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1	265.6×	0.008	PRKAR1B
Vasopressin regulates renal water homeostasis via Aquaporins	1	265.6×	0.008	PRKAR1B
Cellular responses to mechanical stimuli	1	259.6×	0.008	PRKAR1B
ADORA2B mediated anti-inflammatory cytokines production	1	253.8×	0.008	PRKAR1B
GPER1 signaling	1	248.3×	0.008	PRKAR1B
Regulation of insulin secretion	1	219.6×	0.009	PRKAR1B
Post NMDA receptor activation events	1	203.9×	0.009	PRKAR1B
Activation of NMDA receptors and postsynaptic events	1	184.2×	0.009	PRKAR1B
Signaling by Hedgehog	1	184.2×	0.009	PRKAR1B
Hedgehog ‘off’ state	1	178.4×	0.009	PRKAR1B
Integration of energy metabolism	1	175.7×	0.009	PRKAR1B
Leishmania infection	1	163.1×	0.009	PRKAR1B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of fear response	1	8426.0×	0.002	PRKAR1B
regulation of synaptic vesicle cycle	1	561.7×	0.005	PRKAR1B
inner dynein arm assembly	1	443.5×	0.005	DNAAF5
cellular response to glucagon stimulus	1	421.3×	0.005	PRKAR1B
outer dynein arm assembly	1	366.4×	0.005	DNAAF5
vascular endothelial cell response to laminar fluid shear stress	1	366.4×	0.005	PRKAR1B
positive regulation of long-term synaptic potentiation	1	337.0×	0.005	PRKAR1B
negative regulation of inflammatory response to antigenic stimulus	1	300.9×	0.005	PRKAR1B
negative regulation of cAMP/PKA signal transduction	1	300.9×	0.005	PRKAR1B
positive regulation of excitatory postsynaptic potential	1	263.3×	0.005	PRKAR1B
renal water homeostasis	1	255.3×	0.005	PRKAR1B
cilium movement	1	195.9×	0.006	DNAAF5
learning or memory	1	120.4×	0.010	PRKAR1B
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	56.5×	0.019	PRKAR1B
chemical synaptic transmission	1	38.6×	0.026	PRKAR1B

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DNAAF5	0	0
CPLX1-AS1	0	0
PRKAR1B	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PRKAR1B	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	3	DNAAF5, CPLX1-AS1, PRKAR1B

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
DNAAF5	0	—
CPLX1-AS1	0	—
PRKAR1B	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.