Primary ciliary dyskinesia 15

Summary

Primary ciliary dyskinesia 15 (MONDO:0013435) is a disease caused by CCDC40 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: CCDC40 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 232

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 15
Mondo ID	MONDO:0013435
OMIM	613808
DOID	DOID:0110623
NCIT	C155999
UMLS	C3151137
MedGen	462487
GARD	0015714
Is cancer (heuristic)	no

Also known as: CCDC40 primary ciliary dyskinesia · CILD15 · ciliary dyskinesia, primary, 15 · ciliary dyskinesia, primary, type 15 · primary ciliary dyskinesia 15 · primary ciliary dyskinesia caused by mutation in CCDC40 · primary ciliary dyskinesia type 15

Data availability: 232 ClinVar variants · 5 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › primary ciliary dyskinesia › primary ciliary dyskinesia 15

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 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

232 retrieved; paginated sample, class counts are floors:

83 uncertain significance, 56 conflicting classifications of pathogenicity, 32 benign, 17 pathogenic, 17 benign/likely benign, 15 likely pathogenic, 7 pathogenic/likely pathogenic, 5 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1371496	NM_017950.4(CCDC40):c.3175C>T (p.Arg1059Ter)	CCDC40	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1704368	NM_017950.4(CCDC40):c.2753_2754del (p.Lys918fs)	CCDC40	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1704380	NM_017950.4(CCDC40):c.798del (p.Ser267fs)	CCDC40	Pathogenic	criteria provided, single submitter
194774	NM_017950.4(CCDC40):c.2824_2825insCTGT (p.Arg942fs)	CCDC40	Pathogenic	criteria provided, multiple submitters, no conflicts
195522	NM_017950.4(CCDC40):c.3354C>A (p.Tyr1118Ter)	CCDC40	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
216118	NM_017950.4(CCDC40):c.961C>T (p.Arg321Ter)	CCDC40	Pathogenic	criteria provided, multiple submitters, no conflicts
2431510	NM_017950.4(CCDC40):c.1266_1281dup (p.Glu428fs)	CCDC40	Pathogenic	criteria provided, single submitter
2505169	NM_017950.4(CCDC40):c.2619+45G>A	CCDC40	Pathogenic	criteria provided, single submitter
2505170	NM_017950.4(CCDC40):c.2236-213_2832+2269del	CCDC40	Pathogenic	criteria provided, single submitter
2885552	NM_017950.4(CCDC40):c.1571del (p.Gln524fs)	CCDC40	Pathogenic	criteria provided, multiple submitters, no conflicts
31069	NM_017950.4(CCDC40):c.248del (p.Ala83fs)	CCDC40	Pathogenic	criteria provided, multiple submitters, no conflicts
31071	NM_017950.4(CCDC40):c.1951C>T (p.Gln651Ter)	CCDC40	Pathogenic	criteria provided, single submitter
31072	NM_017950.4(CCDC40):c.1345C>T (p.Arg449Ter)	CCDC40	Pathogenic	criteria provided, multiple submitters, no conflicts
407769	NM_017950.4(CCDC40):c.2712-1G>T	CCDC40	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
407770	NM_017950.4(CCDC40):c.1276G>T (p.Glu426Ter)	CCDC40	Pathogenic	criteria provided, multiple submitters, no conflicts
4818928	NM_017950.4(CCDC40):c.2449+2_2449+5del	CCDC40	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4820086	NM_017950.4(CCDC40):c.1820_1823del (p.Leu607fs)	CCDC40	Pathogenic	criteria provided, single submitter
572208	NM_017950.4(CCDC40):c.424C>T (p.Gln142Ter)	CCDC40	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
573257	NM_017950.4(CCDC40):c.3129del (p.Phe1044fs)	CCDC40	Pathogenic	criteria provided, multiple submitters, no conflicts
574268	NM_017950.4(CCDC40):c.1312A>T (p.Lys438Ter)	CCDC40	Pathogenic	criteria provided, multiple submitters, no conflicts
581475	NM_017950.4(CCDC40):c.1416del (p.Ile473fs)	CCDC40	Pathogenic	criteria provided, multiple submitters, no conflicts
65930	NM_017950.4(CCDC40):c.2824_2825insTGT (p.Arg942delinsMetTrp)	CCDC40	Pathogenic	no assertion criteria provided
661903	NM_017950.4(CCDC40):c.3004dup (p.Ile1002fs)	CCDC40	Pathogenic	criteria provided, multiple submitters, no conflicts
851615	NM_017950.4(CCDC40):c.940-1G>C	CCDC40	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1698795	NM_017950.4(CCDC40):c.2257dup (p.Glu753fs)	CCDC40	Likely pathogenic	criteria provided, single submitter
1698886	NM_017950.4(CCDC40):c.3092_3093dup (p.Glu1032Ter)	CCDC40	Likely pathogenic	criteria provided, single submitter
2438898	NM_017950.4(CCDC40):c.833dup (p.Val279fs)	CCDC40	Likely pathogenic	criteria provided, single submitter
3235033	NM_017950.4(CCDC40):c.2476C>T (p.Gln826Ter)	CCDC40	Likely pathogenic	criteria provided, single submitter
3362702	NM_017950.4(CCDC40):c.2026C>T (p.Gln676Ter)	CCDC40	Likely pathogenic	criteria provided, single submitter
3383203	NM_017950.4(CCDC40):c.3058G>T (p.Glu1020Ter)	CCDC40	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · 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
CCDC40	Definitive	Autosomal recessive	primary ciliary dyskinesia 15	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CCDC40	Orphanet:244	Primary ciliary dyskinesia
STEAP3	Orphanet:300298	Severe congenital hypochromic anemia with ringed sideroblasts

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
CCDC40	HGNC:26090	ENSG00000141519	Q4G0X9	Coiled-coil domain-containing protein 40	gencc,clinvar
STEAP3	HGNC:24592	ENSG00000115107	Q658P3	Metalloreductase STEAP3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CCDC40	Coiled-coil domain-containing protein 40	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.
STEAP3	Metalloreductase STEAP3	Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the membrane.

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)
CCDC40	Other/Unknown	no		CCDC40
STEAP3	Other/Unknown	no		Fe3_Rdtase_TM_dom, P5C_Rdtase_cat_N, NAD(P)-bd_dom_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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
right uterine tube	1
sural nerve	1
dorsal root ganglion	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CCDC40	184	ubiquitous	marker	right uterine tube, bronchial epithelial cell, sural nerve
STEAP3	259	ubiquitous	marker	right lobe of liver, liver, dorsal root ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CCDC40	1,527
STEAP3	1,479

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
STEAP3	Q658P3	2
CCDC40	Q4G0X9	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 2 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
TP53 Regulates Transcription of Cell Death Genes	1	543.8×	0.012	STEAP3
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	1	543.8×	0.012	STEAP3
Transferrin endocytosis and recycling	1	368.4×	0.012	STEAP3
Iron uptake and transport	1	346.1×	0.012	STEAP3
RHOF GTPase cycle	1	259.6×	0.012	STEAP3
RHOD GTPase cycle	1	203.9×	0.012	STEAP3
RHOJ GTPase cycle	1	200.3×	0.012	STEAP3
RHOQ GTPase cycle	1	181.3×	0.012	STEAP3
CDC42 GTPase cycle	1	72.3×	0.027	STEAP3
Transcriptional Regulation by TP53	1	62.1×	0.027	STEAP3
RHO GTPase cycle	1	60.1×	0.027	STEAP3
Signaling by Rho GTPases	1	34.2×	0.041	STEAP3
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.041	STEAP3
Transport of small molecules	1	25.1×	0.051	STEAP3
RNA Polymerase II Transcription	1	22.5×	0.053	STEAP3
Gene expression (Transcription)	1	17.8×	0.063	STEAP3
Generic Transcription Pathway	1	15.1×	0.070	STEAP3
Signal Transduction	1	10.2×	0.098	STEAP3

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
determination of pancreatic left/right asymmetry	1	1685.2×	0.004	CCDC40
determination of digestive tract left/right asymmetry	1	1404.3×	0.004	CCDC40
determination of liver left/right asymmetry	1	1404.3×	0.004	CCDC40
copper ion import	1	1203.7×	0.004	STEAP3
regulation of cilium beat frequency	1	1053.2×	0.004	CCDC40
epithelial cilium movement involved in determination of left/right asymmetry	1	648.1×	0.005	CCDC40
axonemal dynein complex assembly	1	526.6×	0.005	CCDC40
iron ion transport	1	443.5×	0.005	STEAP3
inner dynein arm assembly	1	443.5×	0.005	CCDC40
epithelial cilium movement involved in extracellular fluid movement	1	383.0×	0.005	CCDC40
cilium organization	1	300.9×	0.006	CCDC40
motile cilium assembly	1	290.6×	0.006	CCDC40
axoneme assembly	1	271.8×	0.006	CCDC40
protein localization to cilium	1	200.6×	0.007	CCDC40
cilium movement	1	195.9×	0.007	CCDC40
heart looping	1	133.8×	0.009	CCDC40
protein secretion	1	131.7×	0.009	STEAP3
lung development	1	99.1×	0.011	CCDC40
flagellated sperm motility	1	58.5×	0.018	CCDC40
apoptotic process	1	14.3×	0.068	STEAP3

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
CCDC40	0	0
STEAP3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	CCDC40, STEAP3

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)
CCDC40	0	—
STEAP3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.