Primary ciliary dyskinesia 13

Summary

Primary ciliary dyskinesia 13 (MONDO:0013174) is a disease caused by DNAAF1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: DNAAF1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 131

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 13
Mondo ID	MONDO:0013174
MeSH	C567713
OMIM	613193
DOID	DOID:0110618
UMLS	C2750790
MedGen	413399
GARD	0015628
Is cancer (heuristic)	no

Also known as: CILD13 · ciliary dyskinesia, primary, 13 · ciliary dyskinesia, primary, type 13 · DNAAF1 primary ciliary dyskinesia · primary ciliary dyskinesia 13 · primary ciliary dyskinesia caused by mutation in DNAAF1 · primary ciliary dyskinesia type 13

Data availability: 131 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 13

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 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

131 retrieved; paginated sample, class counts are floors:

48 uncertain significance, 32 conflicting classifications of pathogenicity, 18 benign, 14 benign/likely benign, 10 pathogenic, 4 likely pathogenic, 2 likely benign, 2 pathogenic/likely pathogenic, 1 likely pathogenic, low penetrance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1012299	NM_178452.6(DNAAF1):c.1496del (p.Pro499fs)	DNAAF1	Pathogenic	criteria provided, single submitter
1012300	NM_178452.6(DNAAF1):c.1930A>T (p.Arg644Ter)	DNAAF1	Pathogenic	criteria provided, single submitter
263	NM_178452.6(DNAAF1):c.1349dup (p.Pro451fs)	DNAAF1	Pathogenic	criteria provided, single submitter
264	NM_178452.6(DNAAF1):c.811C>T (p.Arg271Ter)	DNAAF1	Pathogenic	criteria provided, single submitter
265	NM_178452.6(DNAAF1):c.792C>A (p.Tyr264Ter)	DNAAF1	Pathogenic	criteria provided, multiple submitters, no conflicts
266	NM_178452.6(DNAAF1):c.508dup (p.Glu170fs)	DNAAF1	Pathogenic	criteria provided, single submitter
267	NM_178452.6(DNAAF1):c.524T>G (p.Leu175Arg)	DNAAF1	Pathogenic	no assertion criteria provided
3775194	NM_178452.6(DNAAF1):c.1282G>T (p.Glu428Ter)	DNAAF1	Pathogenic	criteria provided, single submitter
4537395	NM_178452.6(DNAAF1):c.871dup (p.Ala291fs)	DNAAF1	Pathogenic	criteria provided, single submitter
454995	NM_178452.6(DNAAF1):c.1012del (p.Arg338fs)	DNAAF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
525404	NM_178452.6(DNAAF1):c.1300_1322del (p.Gly434fs)	DNAAF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
65498	NM_178452.6(DNAAF1):c.124+1536_353-2102del	DNAAF1	Pathogenic	no assertion criteria provided
4755471	NM_178452.6(DNAAF1):c.1031-2A>G	DNAAF1	Likely pathogenic	criteria provided, single submitter
4796732	NM_178452.6(DNAAF1):c.524T>C (p.Leu175Pro)	DNAAF1	Likely pathogenic, low penetrance	no assertion criteria provided
4845745	NM_178452.6(DNAAF1):c.1416_1417del (p.Leu473fs)	DNAAF1	Likely pathogenic	criteria provided, single submitter
4845755	NM_178452.6(DNAAF1):c.2065+1G>A	DNAAF1	Likely pathogenic	criteria provided, single submitter
4849381	NM_178452.6(DNAAF1):c.740T>A (p.Leu247Ter)	DNAAF1	Likely pathogenic	criteria provided, single submitter
166997	NM_178452.6(DNAAF1):c.546C>G (p.Asn182Lys)	DNAAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
216831	NM_178452.6(DNAAF1):c.1354C>A (p.Pro452Thr)	DNAAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
242156	NM_178452.6(DNAAF1):c.1031-5A>T	DNAAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
242157	NM_178452.6(DNAAF1):c.1350G>A (p.Pro450=)	DNAAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
242158	NM_178452.6(DNAAF1):c.1495C>A (p.Pro499Thr)	DNAAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
242159	NM_178452.6(DNAAF1):c.1698+1G>A	DNAAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
242161	NM_178452.6(DNAAF1):c.2082C>T (p.Ala694=)	DNAAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
262938	NM_178452.6(DNAAF1):c.1227T>G (p.Gly409=)	DNAAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
262939	NM_178452.6(DNAAF1):c.1299C>T (p.Asp433=)	DNAAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
262941	NM_178452.6(DNAAF1):c.1496C>T (p.Pro499Leu)	DNAAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
262951	NM_178452.6(DNAAF1):c.303G>C (p.Lys101Asn)	DNAAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
262955	NM_178452.6(DNAAF1):c.507G>C (p.Leu169=)	DNAAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
286678	NM_178452.6(DNAAF1):c.1567G>A (p.Val523Ile)	DNAAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
DNAAF1	Strong	Autosomal recessive	primary ciliary dyskinesia 13	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNAAF1	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
DNAAF1	HGNC:30539	ENSG00000154099	Q8NEP3	Dynein axonemal assembly factor 1	gencc,clinvar
TAF1C	HGNC:11534	ENSG00000103168	Q15572	TATA box-binding protein-associated factor RNA polymerase I subunit C	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNAAF1	Dynein axonemal assembly factor 1	Cilium-specific protein required for the stability of the ciliary architecture.
TAF1C	TATA box-binding protein-associated factor RNA polymerase I subunit C	Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (pre-initiation complex) during RNA polymerase I-dependent transcription.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · 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	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNAAF1	Other/Unknown	no		Leu-rich_rpt, LRR_dom_sf, Cilia_flagella_integrity
TAF1C	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf, TAF1C

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
epithelium of bronchus	1
right uterine tube	1
body of uterus	1
left ovary	1
right ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNAAF1	201	broad	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus
TAF1C	242	ubiquitous	marker	left ovary, right ovary, body of uterus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TAF1C	2,006
DNAAF1	809

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TAF1C	Q15572	64.79
DNAAF1	Q8NEP3	61.56

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
Positive epigenetic regulation of rRNA expression	1	346.1×	0.009	TAF1C
RNA Polymerase I Transcription Termination	1	326.3×	0.009	TAF1C
RNA Polymerase I Promoter Clearance	1	292.8×	0.009	TAF1C
RNA Polymerase I Transcription	1	285.5×	0.009	TAF1C
Negative epigenetic regulation of rRNA expression	1	259.6×	0.009	TAF1C
RNA Polymerase I Transcription Initiation	1	223.9×	0.009	TAF1C
SIRT1 negatively regulates rRNA expression	1	170.4×	0.010	TAF1C
B-WICH complex positively regulates rRNA expression	1	121.5×	0.011	TAF1C
RNA Polymerase I Promoter Escape	1	121.5×	0.011	TAF1C
NoRC negatively regulates rRNA expression	1	104.8×	0.011	TAF1C
Epigenetic regulation of gene expression	1	71.4×	0.015	TAF1C
Gene expression (Transcription)	1	17.8×	0.056	TAF1C

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×	0.003	DNAAF1
left/right pattern formation	1	1685.2×	0.003	DNAAF1
determination of digestive tract left/right asymmetry	1	1404.3×	0.003	DNAAF1
determination of liver left/right asymmetry	1	1404.3×	0.003	DNAAF1
regulation of cilium beat frequency	1	1053.2×	0.003	DNAAF1
transcription initiation at RNA polymerase I promoter	1	936.2×	0.003	TAF1C
transcription by RNA polymerase I	1	702.2×	0.003	TAF1C
epithelial cilium movement involved in determination of left/right asymmetry	1	648.1×	0.003	DNAAF1
axonemal dynein complex assembly	1	526.6×	0.004	DNAAF1
inner dynein arm assembly	1	443.5×	0.004	DNAAF1
outer dynein arm assembly	1	366.4×	0.004	DNAAF1
motile cilium assembly	1	290.6×	0.005	DNAAF1
axoneme assembly	1	271.8×	0.005	DNAAF1
cilium movement	1	195.9×	0.007	DNAAF1
heart looping	1	133.8×	0.009	DNAAF1
lung development	1	99.1×	0.011	DNAAF1
cilium assembly	1	36.8×	0.028	DNAAF1
transcription by RNA polymerase II	1	35.3×	0.028	TAF1C

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
DNAAF1	0	0
TAF1C	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	DNAAF1, TAF1C

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)
DNAAF1	0	—
TAF1C	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.