Primary ciliary dyskinesia 2

Summary

Primary ciliary dyskinesia 2 (MONDO:0011718) is a disease caused by DNAAF3 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: DNAAF3 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 47

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 2
Mondo ID	MONDO:0011718
MeSH	C535277
OMIM	606763
DOID	DOID:0110626
UMLS	C1847554
MedGen	338258
GARD	0015400
Is cancer (heuristic)	no

Also known as: CILD2 · ciliary dyskinesia, primary, 2 · ciliary dyskinesia, primary, type 2 · DNAAF3 primary ciliary dyskinesia · primary ciliary dyskinesia caused by mutation in DNAAF3 · primary ciliary dyskinesia type 2

Data availability: 47 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 2

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 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 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

47 retrieved; paginated sample, class counts are floors:

14 uncertain significance, 12 benign/likely benign, 6 pathogenic, 5 pathogenic/likely pathogenic, 3 likely pathogenic, 3 likely benign, 3 conflicting classifications of pathogenicity, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1073351	NM_001256715.2(DNAAF3):c.1195del (p.Ala399fs)	DNAAF3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324262	NM_001256715.2(DNAAF3):c.901C>T (p.Gln301Ter)	DNAAF3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1331503	NM_001256715.2(DNAAF3):c.548_558dup (p.Ser187delinsArgSerProTer)	DNAAF3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2664320	NM_001256715.2(DNAAF3):c.76C>T (p.Gln26Ter)	DNAAF3	Pathogenic	criteria provided, single submitter
31532	NM_001256715.2(DNAAF3):c.182T>C (p.Leu61Pro)	DNAAF3	Pathogenic	criteria provided, single submitter
31533	NM_001256715.2(DNAAF3):c.265C>T (p.Arg89Ter)	DNAAF3	Pathogenic	criteria provided, multiple submitters, no conflicts
410279	NM_001256715.2(DNAAF3):c.997dup (p.Asp333fs)	DNAAF3	Pathogenic	criteria provided, multiple submitters, no conflicts
495054	NM_001256715.2(DNAAF3):c.1271dup (p.Phe426fs)	DNAAF3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
572342	NM_001256715.2(DNAAF3):c.350G>A (p.Trp117Ter)	DNAAF3	Pathogenic	criteria provided, multiple submitters, no conflicts
31534	NM_001256715.2(DNAAF3):c.621dup (p.Val208fs)	DNAAF3-AS1	Pathogenic	no assertion criteria provided
410288	NM_001256715.2(DNAAF3):c.607_611dup (p.Arg205fs)	DNAAF3-AS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324264	NM_001256714.1(DNAAF3):c.23C>A (p.Ser8Ter)	DNAAF3	Likely pathogenic	criteria provided, single submitter
2690909	NM_001256715.2(DNAAF3):c.366_430del (p.Val126fs)	DNAAF3	Likely pathogenic	criteria provided, single submitter
4081336	NM_001256715.2(DNAAF3):c.196C>T (p.Arg66Ter)	DNAAF3	Likely pathogenic	criteria provided, single submitter
330207	NM_001256715.2(DNAAF3):c.1589C>T (p.Pro530Leu)	DNAAF3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3584070	NM_001256715.2(DNAAF3):c.24C>T (p.Gly8=)	DNAAF3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
454613	NM_001256715.2(DNAAF3):c.1041_1048+1del	DNAAF3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1380639	NM_001256715.2(DNAAF3):c.322G>A (p.Glu108Lys)	DNAAF3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1442743	NM_001256715.2(DNAAF3):c.851C>A (p.Ala284Asp)	DNAAF3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1768171	NM_001256715.2(DNAAF3):c.773G>C (p.Gly258Ala)	DNAAF3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1981698	NM_001256715.2(DNAAF3):c.871G>A (p.Asp291Asn)	DNAAF3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3064740	NM_001256715.2(DNAAF3):c.856G>A (p.Gly286Ser)	DNAAF3	Uncertain significance	criteria provided, single submitter
330214	NM_001256715.2(DNAAF3):c.890C>T (p.Thr297Met)	DNAAF3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3382266	NM_001256715.2(DNAAF3):c.289G>C (p.Ala97Pro)	DNAAF3	Uncertain significance	criteria provided, single submitter
3584069	NM_001256715.2(DNAAF3):c.1328C>T (p.Thr443Ile)	DNAAF3	Uncertain significance	criteria provided, single submitter
454620	NM_001256715.2(DNAAF3):c.1626A>G (p.Ter542Trp)	DNAAF3	Uncertain significance	criteria provided, multiple submitters, no conflicts
4685599	NM_001256715.2(DNAAF3):c.1586C>A (p.Ala529Asp)	DNAAF3	Uncertain significance	criteria provided, multiple submitters, no conflicts
941083	NM_001256715.2(DNAAF3):c.782T>C (p.Leu261Pro)	DNAAF3	Uncertain significance	criteria provided, multiple submitters, no conflicts
969929	NM_001256715.2(DNAAF3):c.469C>T (p.Arg157Cys)	DNAAF3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2440894	NM_001256715.2(DNAAF3):c.1312G>T (p.Gly438Ter)	DNAAF3-AS1	Uncertain significance	criteria provided, single submitter

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
DNAAF3	Definitive	Autosomal recessive	primary ciliary dyskinesia 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNAAF3	Orphanet:244	Primary ciliary dyskinesia
DNAH1	Orphanet:244	Primary ciliary dyskinesia
DNAH1	Orphanet:276234	Non-syndromic male infertility due to sperm motility disorder

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
DNAAF3	HGNC:30492	ENSG00000167646	Q8N9W5	Dynein axonemal assembly factor 3	gencc,clinvar
DNAH1	HGNC:2940	ENSG00000114841	Q9P2D7	Dynein axonemal heavy chain 1	clinvar
DNAAF3-AS1	HGNC:55292	ENSG00000267577		DNAAF3 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNAAF3	Dynein axonemal assembly factor 3	Required for the assembly of axonemal inner and outer dynein arms.
DNAH1	Dynein axonemal heavy chain 1	Force generating protein of cilia required for sperm flagellum motility.

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)
DNAAF3	Other/Unknown	no		DUF4470, DNAAF3_C, DNAAF3
DNAH1	Other/Unknown	no		Dhc_D6_P-loop, Dhc_linker, Dhc_D4
DNAAF3-AS1	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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	2
right uterine tube	2
right testis	1
bronchial epithelial cell	1
bronchus	1
male germ line stem cell (sensu Vertebrata) in testis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNAAF3	158	broad	marker	apex of heart, right uterine tube, right testis
DNAH1	183	tissue_specific	marker	right uterine tube, bronchial epithelial cell, bronchus
DNAAF3-AS1	110		yes	sperm, apex of heart, 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
DNAH1	1,699
DNAAF3	794
DNAAF3-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DNAH1	Q9P2D7	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DNAAF3	Q8N9W5	81.06

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 3 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cilium-dependent cell motility	1	702.2×	0.007	DNAH1
axonemal dynein complex assembly	1	526.6×	0.007	DNAAF3
inner dynein arm assembly	1	443.5×	0.007	DNAH1
cerebrospinal fluid circulation	1	443.5×	0.007	DNAAF3
epithelial cilium movement involved in extracellular fluid movement	1	383.0×	0.007	DNAH1
seminiferous tubule development	1	383.0×	0.007	DNAAF3
motile cilium assembly	1	290.6×	0.008	DNAAF3
sperm axoneme assembly	1	234.1×	0.009	DNAH1
determination of adult lifespan	1	216.1×	0.009	DNAAF3
determination of left/right symmetry	1	127.7×	0.013	DNAAF3
lung development	1	99.1×	0.016	DNAAF3
cell morphogenesis	1	78.8×	0.018	DNAAF3
multicellular organism growth	1	68.5×	0.019	DNAAF3
flagellated sperm motility	1	58.5×	0.021	DNAH1
brain development	1	39.8×	0.027	DNAAF3
heart development	1	39.4×	0.027	DNAAF3
spermatogenesis	1	17.6×	0.056	DNAAF3

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 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
DNAAF3	0	0
DNAH1	0	0
DNAAF3-AS1	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	3	DNAAF3, DNAH1, DNAAF3-AS1

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)
DNAAF3	0	—
DNAH1	0	—
DNAAF3-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.