Primary ciliary dyskinesia 20

Summary

Primary ciliary dyskinesia 20 (MONDO:0014030) is a disease caused by ODAD1 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: ODAD1 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 44

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 20
Mondo ID	MONDO:0014030
OMIM	615067
DOID	DOID:0110625
UMLS	C3540844
MedGen	761920
GARD	0015902
Is cancer (heuristic)	no

Also known as: CCDC114 primary ciliary dyskinesia · CILD20 · ciliary dyskinesia, primary, 20 · ciliary dyskinesia, primary, type 20 · primary ciliary dyskinesia caused by mutation in CCDC114 · primary ciliary dyskinesia type 20

Data availability: 44 ClinVar variants · 2 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 20

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 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

44 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 8 benign, 7 pathogenic/likely pathogenic, 7 benign/likely benign, 5 conflicting classifications of pathogenicity, 5 pathogenic, 3 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1322037	NM_001364171.2(ODAD1):c.742C>T (p.Gln248Ter)	ODAD1	Pathogenic	criteria provided, single submitter
1324024	NM_001364171.2(ODAD1):c.448C>T (p.Arg150Ter)	ODAD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1682898	NM_001364171.2(ODAD1):c.358C>T (p.Gln120Ter)	ODAD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2630887	NM_001364171.2(ODAD1):c.813_816dup (p.Pro273fs)	ODAD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3248621	NM_001364171.2(ODAD1):c.1246C>T (p.Gln416Ter)	ODAD1	Pathogenic	criteria provided, single submitter
3383099	NM_001364171.2(ODAD1):c.71-2A>C	ODAD1	Pathogenic	criteria provided, single submitter
39637	NM_001364171.2(ODAD1):c.853G>A (p.Ala285Thr)	ODAD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39638	NM_001364171.2(ODAD1):c.597+1G>A	ODAD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39639	NM_001364171.2(ODAD1):c.598-2A>G	ODAD1	Pathogenic	criteria provided, multiple submitters, no conflicts
39640	NM_001364171.2(ODAD1):c.1502+5G>A	ODAD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39641	NM_001364171.2(ODAD1):c.1050del (p.His350fs)	ODAD1	Pathogenic	criteria provided, single submitter
128117	NM_024675.4(PALB2):c.1240C>T (p.Arg414Ter)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1723223	NM_001364171.2(ODAD1):c.97C>T (p.Arg33Ter)	ODAD1	Likely pathogenic	criteria provided, single submitter
2687745	NM_001364171.2(ODAD1):c.1057dup (p.Glu353fs)	ODAD1	Likely pathogenic	criteria provided, single submitter
3893032	NM_001364171.2(ODAD1):c.598-2A>C	ODAD1	Likely pathogenic	criteria provided, single submitter
1000564	NM_001364171.2(ODAD1):c.707C>T (p.Ala236Val)	ODAD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1682897	NM_001364171.2(ODAD1):c.377C>T (p.Thr126Met)	ODAD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
454964	NM_001364171.2(ODAD1):c.1423G>A (p.Asp475Asn)	ODAD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
525427	NM_001364171.2(ODAD1):c.1198C>T (p.Arg400Cys)	ODAD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
569031	NM_002582.4(PARN):c.466G>T (p.Ala156Ser)	PARN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1682854	NM_001364171.2(ODAD1):c.2004dup (p.Gly669fs)	ODAD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1682902	NM_001364171.2(ODAD1):c.226G>A (p.Ala76Thr)	ODAD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2920669	NM_001364171.2:c.(360+1_361-1)_(597+1_597-1)del	ODAD1	Uncertain significance	criteria provided, single submitter
406183	NM_001364171.2(ODAD1):c.498_499insCGT (p.Phe166_Asp167insArg)	ODAD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
525277	NM_001364171.2(ODAD1):c.1016A>G (p.Asn339Ser)	ODAD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
662204	NM_001364171.2(ODAD1):c.1822C>T (p.His608Tyr)	ODAD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
691976	NM_001364171.2(ODAD1):c.1336C>T (p.Leu446Phe)	ODAD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
953164	NM_001364171.2(ODAD1):c.991G>A (p.Glu331Lys)	ODAD1	Uncertain significance	criteria provided, multiple submitters, no conflicts
241868	NM_001364171.2(ODAD1):c.1214G>A (p.Arg405Gln)	ODAD1	Benign	criteria provided, multiple submitters, no conflicts
241871	NM_001364171.2(ODAD1):c.1630G>A (p.Ala544Thr)	ODAD1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 9 · 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
ODAD1	Definitive	Autosomal recessive	primary ciliary dyskinesia 20	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ODAD1	Orphanet:244	Primary ciliary dyskinesia
PALB2	Orphanet:1333	Familial pancreatic carcinoma
PALB2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
PALB2	Orphanet:178	Chordoma
PALB2	Orphanet:227535	Hereditary breast cancer
PALB2	Orphanet:84	Fanconi anemia
PARN	Orphanet:1775	Dyskeratosis congenita
PARN	Orphanet:2032	Idiopathic pulmonary fibrosis
PARN	Orphanet:3322	Hoyeraal-Hreidarsson syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ODAD1	HGNC:26560	ENSG00000105479	Q96M63	Outer dynein arm-docking complex subunit 1	gencc,clinvar
PALB2	HGNC:26144	ENSG00000083093	Q86YC2	Partner and localizer of BRCA2	clinvar
PARN	HGNC:8609	ENSG00000140694	O95453	Poly(A)-specific ribonuclease PARN	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ODAD1	Outer dynein arm-docking complex subunit 1	Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule.
PALB2	Partner and localizer of BRCA2	Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks.
PARN	Poly(A)-specific ribonuclease PARN	3’-exoribonuclease that has a preference for poly(A) tails of mRNAs, thereby efficiently degrading poly(A) tails.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Scaffold/PPI	1	5.8×	0.327
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ODAD1	Other/Unknown	no		ODAD1_CC, ODA-DC/CCD
PALB2	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, PALB2_WD40, WD40_repeat_dom_sf
PARN	Other/Unknown	no		R3H_dom, RNase_CAF1, RNaseH-like_sf

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
oviduct epithelium	1
right uterine tube	1
buccal mucosa cell	1
oocyte	1
secondary oocyte	1
calcaneal tendon	1
corpus callosum	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ODAD1	174	broad	marker	oviduct epithelium, right uterine tube, bronchial epithelial cell
PALB2	232	ubiquitous	yes	secondary oocyte, buccal mucosa cell, oocyte
PARN	134	ubiquitous	marker	calcaneal tendon, corpus callosum, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PALB2	5,641
PARN	1,532
ODAD1	1,224

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PALB2	Q86YC2	4
PARN	O95453	3
ODAD1	Q96M63	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
KSRP (KHSRP) binds and destabilizes mRNA	1	317.2×	0.008	PARN
Impaired BRCA2 binding to PALB2	1	228.4×	0.008	PALB2
Deadenylation of mRNA	1	219.6×	0.008	PARN
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	211.5×	0.008	PALB2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	211.5×	0.008	PALB2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	211.5×	0.008	PALB2
ATF4 activates genes in response to endoplasmic reticulum stress	1	203.9×	0.008	PARN
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	196.9×	0.008	PALB2
Homologous DNA Pairing and Strand Exchange	1	190.3×	0.008	PALB2
Resolution of D-loop Structures through Holliday Junction Intermediates	1	150.3×	0.009	PALB2
HDR through Homologous Recombination (HRR)	1	95.2×	0.012	PALB2
KEAP1-NFE2L2 pathway	1	60.1×	0.018	PALB2
Neddylation	1	23.7×	0.042	PALB2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
box H/ACA sno(s)RNA 3’-end processing	1	2808.7×	0.002	PARN
RNA modification	1	2808.7×	0.002	PARN
lncRNA processing	1	2808.7×	0.002	PARN
priRNA 3’-end processing	1	2808.7×	0.002	PARN
siRNA 3’-end processing	1	2808.7×	0.002	PARN
telomerase RNA stabilization	1	1404.3×	0.003	PARN
regulation of telomerase RNA localization to Cajal body	1	1404.3×	0.003	PARN
poly(A)-dependent snoRNA 3’-end processing	1	702.2×	0.004	PARN
miRNA catabolic process	1	624.1×	0.004	PARN
inner cell mass cell proliferation	1	330.4×	0.007	PALB2
nuclear-transcribed mRNA poly(A) tail shortening	1	267.5×	0.007	PARN
female gamete generation	1	267.5×	0.007	PARN
positive regulation of telomere maintenance via telomerase	1	244.2×	0.007	PARN
outer dynein arm assembly	1	244.2×	0.007	ODAD1
post-anal tail morphogenesis	1	244.2×	0.007	PALB2
mesoderm development	1	175.5×	0.009	PALB2
embryonic organ development	1	160.5×	0.009	PALB2
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	1	156.0×	0.009	PARN
cilium movement	1	130.6×	0.010	ODAD1
somitogenesis	1	124.8×	0.010	PALB2
animal organ morphogenesis	1	63.8×	0.019	PALB2
double-strand break repair via homologous recombination	1	52.0×	0.022	PALB2
multicellular organism growth	1	45.7×	0.024	PALB2
negative regulation of apoptotic process	1	11.6×	0.087	PALB2
apoptotic process	1	9.6×	0.101	PALB2

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
ODAD1	0	0
PALB2	0	0
PARN	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
PARN	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	ODAD1, PALB2, PARN

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)
ODAD1	0	—
PALB2	0	—
PARN	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.