Primary ciliary dyskinesia 14

Summary

Primary ciliary dyskinesia 14 (MONDO:0013434) is a disease caused by CCDC39 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: CCDC39 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 182

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 14
Mondo ID	MONDO:0013434
OMIM	613807
DOID	DOID:0110598
NCIT	C148370
UMLS	C3151136
MedGen	462486
GARD	0015713
Is cancer (heuristic)	no

Also known as: CCDC39 primary ciliary dyskinesia · CILD14 · ciliary dyskinesia, primary, 14 · ciliary dyskinesia, primary, type 14 · primary ciliary dyskinesia 14 · primary ciliary dyskinesia caused by mutation in CCDC39 · primary ciliary dyskinesia type 14

Data availability: 182 ClinVar variants · 3 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 14

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 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 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

182 retrieved; paginated sample, class counts are floors:

54 uncertain significance, 45 conflicting classifications of pathogenicity, 24 likely pathogenic, 18 pathogenic, 17 benign, 15 pathogenic/likely pathogenic, 8 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1012311	NM_181426.2(CCDC39):c.2040_2043del (p.Cys680fs)	CCDC39	Pathogenic	criteria provided, multiple submitters, no conflicts
1070026	NM_181426.2(CCDC39):c.1964_1968del (p.Glu655fs)	CCDC39	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322038	NM_181426.2(CCDC39):c.1999-2A>T	CCDC39	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322039	NM_181426.2(CCDC39):c.2061dup (p.Ala688fs)	CCDC39	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322040	NM_181426.2(CCDC39):c.1456dup (p.Glu486fs)	CCDC39	Pathogenic	criteria provided, single submitter
1371704	NM_181426.2(CCDC39):c.1540_1544del (p.Phe514fs)	CCDC39	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188300	NM_181426.2(CCDC39):c.526_527del (p.Leu176fs)	CCDC39	Pathogenic	criteria provided, multiple submitters, no conflicts
1916247	NM_181426.2(CCDC39):c.210+2T>C	CCDC39	Pathogenic	criteria provided, multiple submitters, no conflicts
2001402	NM_181426.2(CCDC39):c.74del (p.Lys25fs)	CCDC39	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
216140	NM_181426.2(CCDC39):c.610-2A>G	CCDC39	Pathogenic	criteria provided, multiple submitters, no conflicts
242176	NM_181426.2(CCDC39):c.830_831del (p.Thr277fs)	CCDC39	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2913307	NM_181426.2(CCDC39):c.2492_2496del (p.Met831fs)	CCDC39	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31067	NM_181426.2(CCDC39):c.357+1G>C	CCDC39	Pathogenic	criteria provided, multiple submitters, no conflicts
3588955	NM_181426.2(CCDC39):c.1714C>T (p.Arg572Ter)	CCDC39	Pathogenic	criteria provided, single submitter
3588960	NM_181426.2(CCDC39):c.1018_1019insG (p.His340fs)	CCDC39	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3768520	NM_181426.2(CCDC39):c.1246G>T (p.Glu416Ter)	CCDC39	Pathogenic	criteria provided, single submitter
410378	NM_181426.2(CCDC39):c.1167+1261A>G	CCDC39	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
419341	NM_181426.2(CCDC39):c.2226C>A (p.Tyr742Ter)	CCDC39	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
455019	NM_181426.2(CCDC39):c.2497_2498del (p.Gln833fs)	CCDC39	Pathogenic	criteria provided, multiple submitters, no conflicts
4755461	NM_181426.2(CCDC39):c.2485del (p.Arg829fs)	CCDC39	Pathogenic	criteria provided, single submitter
525300	NM_181426.2(CCDC39):c.610_613del	CCDC39	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
565319	NM_181426.2(CCDC39):c.1871_1872del (p.Ile624fs)	CCDC39	Pathogenic	criteria provided, multiple submitters, no conflicts
653672	NM_181426.2(CCDC39):c.1848del (p.Arg615_Tyr616insTer)	CCDC39	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
65950	NM_181426.2(CCDC39):c.2190del (p.Glu731fs)	CCDC39	Pathogenic	criteria provided, multiple submitters, no conflicts
65994	NM_181426.2(CCDC39):c.2357_2359delinsT (p.Ser786fs)	CCDC39	Pathogenic	criteria provided, multiple submitters, no conflicts
65998	NM_181426.2(CCDC39):c.1072del (p.Thr358fs)	CCDC39	Pathogenic	criteria provided, multiple submitters, no conflicts
661055	NM_181426.2(CCDC39):c.1045del (p.Thr349fs)	CCDC39	Pathogenic	criteria provided, multiple submitters, no conflicts
838859	NM_181426.2(CCDC39):c.2358_2362del (p.Ser786fs)	CCDC39	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
844752	NM_181426.2(CCDC39):c.2596G>T (p.Glu866Ter)	CCDC39	Pathogenic	criteria provided, multiple submitters, no conflicts
869378	NM_181426.2(CCDC39):c.1244_1261delinsGG (p.Lys415fs)	CCDC39	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
CCDC39	Definitive	Autosomal recessive	primary ciliary dyskinesia 14	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CCDC39	Orphanet:244	Primary ciliary dyskinesia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CCDC39	HGNC:25244	ENSG00000284862	Q9UFE4	Coiled-coil domain-containing protein 39	gencc,clinvar
TTC14	HGNC:24697	ENSG00000163728	Q96N46	Tetratricopeptide repeat protein 14	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CCDC39	Coiled-coil domain-containing protein 39	Required for assembly of dynein regulatory complex (DRC) and inner dynein arm (IDA) complexes, which are responsible for ciliary beat regulation, thereby playing a central role in motility in cilia and flagella.

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)
CCDC39	Other/Unknown	no		CCDC39
TTC14	Other/Unknown	no		S1_domain, TPR-like_helical_dom_sf, NA-bd_OB-fold

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
right uterine tube	2
endometrium	1
olfactory segment of nasal mucosa	1
adenohypophysis	1
epithelial cell of pancreas	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CCDC39	132	tissue_specific	marker	right uterine tube, olfactory segment of nasal mucosa, endometrium
TTC14	260	ubiquitous	marker	epithelial cell of pancreas, right uterine tube, adenohypophysis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TTC14	1,443
CCDC39	1,218

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CCDC39	Q9UFE4	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TTC14	Q96N46	62.21

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
determination of pancreatic left/right asymmetry	1	3370.4×	0.002	CCDC39
determination of digestive tract left/right asymmetry	1	2808.7×	0.002	CCDC39
determination of liver left/right asymmetry	1	2808.7×	0.002	CCDC39
regulation of cilium beat frequency	1	2106.5×	0.002	CCDC39
establishment of left/right asymmetry	1	2106.5×	0.002	CCDC39
microglia differentiation	1	1532.0×	0.002	CCDC39
locomotion	1	1532.0×	0.002	CCDC39
neuroinflammatory response	1	1532.0×	0.002	CCDC39
cilium-dependent cell motility	1	1404.3×	0.002	CCDC39
epithelial cilium movement involved in determination of left/right asymmetry	1	1296.3×	0.002	CCDC39
axonemal dynein complex assembly	1	1053.2×	0.002	CCDC39
central nervous system myelination	1	991.3×	0.002	CCDC39
synapse maturation	1	936.2×	0.002	CCDC39
inner dynein arm assembly	1	887.0×	0.002	CCDC39
cerebrospinal fluid circulation	1	887.0×	0.002	CCDC39
neuron maturation	1	802.5×	0.002	CCDC39
cilium organization	1	601.9×	0.002	CCDC39
motile cilium assembly	1	581.1×	0.002	CCDC39
protein localization to cilium	1	401.2×	0.003	CCDC39
cilium movement	1	391.9×	0.003	CCDC39
neuron projection morphogenesis	1	276.3×	0.004	CCDC39
heart looping	1	267.5×	0.004	CCDC39
cerebral cortex development	1	205.5×	0.005	CCDC39
lung development	1	198.3×	0.005	CCDC39
establishment of localization in cell	1	160.5×	0.006	CCDC39
flagellated sperm motility	1	117.0×	0.009	CCDC39

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CCDC39	0	0
TTC14	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
TTC14	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	2	CCDC39, TTC14

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)
CCDC39	0	—
TTC14	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.