Primary ciliary dyskinesia 17

Summary

Primary ciliary dyskinesia 17 (MONDO:0013854) is a disease caused by DNAAF19 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: DNAAF19 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 54

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 17
Mondo ID	MONDO:0013854
OMIM	614679
DOID	DOID:0110621
UMLS	C3542550
MedGen	762261
GARD	0015835
Is cancer (heuristic)	no

Also known as: CCDC103 primary ciliary dyskinesia · CILD17 · ciliary dyskinesia, primary, 17 · ciliary dyskinesia, primary, type 17 · primary ciliary dyskinesia 17 · primary ciliary dyskinesia caused by mutation in CCDC103 · primary ciliary dyskinesia type 17

Data availability: 54 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 17

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 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

54 retrieved; paginated sample, class counts are floors:

30 uncertain significance, 8 conflicting classifications of pathogenicity, 7 likely pathogenic, 5 pathogenic/likely pathogenic, 2 benign/likely benign, 1 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1344594	NM_213607.3(DNAAF19):c.144-1G>A	DNAAF19	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451307	NM_213607.3(DNAAF19):c.566_569del (p.Glu189fs)	DNAAF19	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453191	NM_213607.3(DNAAF19):c.298G>T (p.Glu100Ter)	DNAAF19	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1797396	NM_213607.3(DNAAF19):c.289dup (p.Leu97fs)	DNAAF19	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31697	NM_213607.3(DNAAF19):c.383dup (p.Pro129fs)	DNAAF19	Pathogenic	no assertion criteria provided
31698	NM_213607.3(DNAAF19):c.461A>C (p.His154Pro)	DNAAF19	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3233633	NM_213607.3(DNAAF19):c.276_276+13del	DNAAF19	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3582146	NM_213607.3(DNAAF19):c.78C>A (p.Tyr26Ter)	DNAAF19	Likely pathogenic	criteria provided, single submitter
3582148	NM_213607.3(DNAAF19):c.197del (p.Gly66fs)	DNAAF19	Likely pathogenic	criteria provided, single submitter
3582149	NM_213607.3(DNAAF19):c.218G>A (p.Trp73Ter)	DNAAF19	Likely pathogenic	criteria provided, single submitter
3582150	NM_213607.3(DNAAF19):c.410_413del (p.Thr137fs)	DNAAF19	Likely pathogenic	criteria provided, single submitter
3582152	NM_213607.3(DNAAF19):c.600del (p.Met201fs)	DNAAF19	Likely pathogenic	criteria provided, single submitter
455029	NM_213607.3(DNAAF19):c.568_569dup (p.Ser190fs)	DNAAF19	Likely pathogenic	criteria provided, multiple submitters, no conflicts
323583	NM_213607.3(DNAAF19):c.513G>A (p.Ala171=)	DNAAF19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
323584	NM_213607.3(DNAAF19):c.606C>A (p.Gly202=)	DNAAF19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
323585	NM_213607.3(DNAAF19):c.627G>A (p.Glu209=)	DNAAF19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
411698	NM_213607.3(DNAAF19):c.275C>T (p.Pro92Leu)	DNAAF19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
525550	NM_213607.3(DNAAF19):c.297C>T (p.Pro99=)	DNAAF19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
699888	NM_213607.3(DNAAF19):c.348G>C (p.Gly116=)	DNAAF19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
888961	NM_213607.3(DNAAF19):c.72G>A (p.Glu24=)	DNAAF19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
955334	NM_213607.3(DNAAF19):c.31G>C (p.Ala11Pro)	DNAAF19	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2074548	NM_213607.3(DNAAF19):c.277G>A (p.Glu93Lys)	DNAAF19	Uncertain significance	criteria provided, multiple submitters, no conflicts
242264	NM_213607.3(DNAAF19):c.359A>G (p.Tyr120Cys)	DNAAF19	Uncertain significance	criteria provided, multiple submitters, no conflicts
2431833	NM_213607.3(DNAAF19):c.332_334delinsCAA (p.Arg111_His112delinsProAsn)	DNAAF19	Uncertain significance	criteria provided, single submitter
323575	NM_213607.2(DNAAF19):c.-150A>G	DNAAF19	Uncertain significance	criteria provided, single submitter
323576	NM_213607.2(DNAAF19):c.-141C>T	DNAAF19	Uncertain significance	criteria provided, single submitter
323577	NM_213607.3(DNAAF19):c.-131C>A	DNAAF19	Uncertain significance	criteria provided, single submitter
323578	NM_213607.3(DNAAF19):c.-113G>A	DNAAF19	Uncertain significance	criteria provided, multiple submitters, no conflicts
323579	NM_213607.3(DNAAF19):c.-74G>C	DNAAF19	Uncertain significance	criteria provided, single submitter
323581	NM_213607.3(DNAAF19):c.-11G>A	DNAAF19	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
DNAAF19	Definitive	Autosomal recessive	primary ciliary dyskinesia 17	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNAAF19	Orphanet:244	Primary ciliary dyskinesia
GFAP	Orphanet:363717	Alexander disease type I
GFAP	Orphanet:363722	Alexander disease type II

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
DNAAF19	HGNC:32700	ENSG00000167131	Q8IW40	Dynein axonemal assembly factor 19	gencc,clinvar
FAM187A	HGNC:35153	ENSG00000214447	A6NFU0	Ig-like V-type domain-containing protein FAM187A	clinvar
GFAP	HGNC:4235	ENSG00000131095	P14136	Glial fibrillary acidic protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNAAF19	Dynein axonemal assembly factor 19	Dynein-attachment factor required for cilia motility.
GFAP	Glial fibrillary acidic protein	GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Antibody/Immunoglobulin	1	9.7×	0.199
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNAAF19	Other/Unknown	no		RPAP3-like_C, Dynein_attach_N, CC103
FAM187A	Antibody/Immunoglobulin	yes		Ig-like_dom, Ig_V-set, Ig-like_fold
GFAP	Other/Unknown	no		Intermed_filament_DNA-bd, IF_conserved, IF_rod_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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
left testis	2
male germ line stem cell (sensu Vertebrata) in testis	2
testis	2
dorsal motor nucleus of vagus nerve	1
inferior olivary complex	1
medulla oblongata	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNAAF19	130	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, left testis, testis
FAM187A	128	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, left testis, testis
GFAP	210	broad	marker	medulla oblongata, inferior olivary complex, dorsal motor nucleus of vagus nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GFAP	6,997
DNAAF19	764
FAM187A	258

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GFAP	P14136	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FAM187A	A6NFU0	83.09
DNAAF19	Q8IW40	80.42

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Chaperone Mediated Autophagy	1	496.5×	0.003	GFAP
Nuclear signaling by ERBB4	1	346.1×	0.003	GFAP

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 Schwann cell proliferation	1	8426.0×	0.003	GFAP
Schwann cell proliferation	1	2808.7×	0.003	GFAP
regulation of neurotransmitter uptake	1	2808.7×	0.003	GFAP
neuron projection regeneration	1	2106.5×	0.003	GFAP
D-aspartate import across plasma membrane	1	1685.2×	0.003	GFAP
regulation of chaperone-mediated autophagy	1	1685.2×	0.003	GFAP
determination of digestive tract left/right asymmetry	1	1404.3×	0.003	DNAAF19
Bergmann glial cell differentiation	1	766.0×	0.004	GFAP
epithelial cilium movement involved in determination of left/right asymmetry	1	648.1×	0.004	DNAAF19
astrocyte development	1	561.7×	0.004	GFAP
axonemal dynein complex assembly	1	526.6×	0.004	DNAAF19
enteric nervous system development	1	495.6×	0.004	GFAP
inner dynein arm assembly	1	443.5×	0.004	DNAAF19
epithelial cilium movement involved in extracellular fluid movement	1	383.0×	0.004	DNAAF19
outer dynein arm assembly	1	366.4×	0.004	DNAAF19
regulation of protein-containing complex assembly	1	366.4×	0.004	GFAP
cilium movement	1	195.9×	0.008	DNAAF19
neural crest cell migration	1	168.5×	0.009	GFAP
long-term synaptic potentiation	1	140.4×	0.010	GFAP
heart looping	1	133.8×	0.010	DNAAF19
determination of left/right symmetry	1	127.7×	0.010	DNAAF19
intermediate filament organization	1	120.4×	0.010	GFAP
negative regulation of neuron projection development	1	118.7×	0.010	GFAP
extracellular matrix organization	1	61.1×	0.018	GFAP
gene expression	1	39.9×	0.026	GFAP
intracellular protein transport	1	32.4×	0.031	GFAP

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
DNAAF19	0	0
FAM187A	0	0
GFAP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	1	FAM187A
E	Difficult family or no structure, no drug	2	DNAAF19, GFAP

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)
DNAAF19	0	—
FAM187A	0	—
GFAP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.