Primary ciliary dyskinesia 1

disease

On this page

Also known as CILD1ciliary dyskinesia, primary, 1ciliary dyskinesia, primary, type 1DNAI1 primary ciliary dyskinesiaPCDprimary ciliary dyskinesia caused by mutation in DNAI1primary ciliary dyskinesia type 1

Summary

Primary ciliary dyskinesia 1 (MONDO:0009484) is a disease caused by DNAI1 (GenCC Strong), with 19 cohort genes.

At a glance

Causal gene: DNAI1 (GenCC Strong)
Cohort genes: 19
ClinVar variants: 168

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 1
Mondo ID	MONDO:0009484
OMIM	244400
Orphanet	98861
DOID	DOID:0110594
NCIT	C128117
UMLS	C4551906
MedGen	1646059
GARD	0024674
Is cancer (heuristic)	no

Also known as: CILD1 · ciliary dyskinesia, primary, 1 · ciliary dyskinesia, primary, type 1 · DNAI1 primary ciliary dyskinesia · PCD · primary ciliary dyskinesia 1 · primary ciliary dyskinesia caused by mutation in DNAI1 · primary ciliary dyskinesia type 1

Data availability: 168 ClinVar variants · 2 GenCC gene-disease records · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › primary ciliary dyskinesia › primary ciliary dyskinesia 1

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

168 retrieved; paginated sample, class counts are floors:

42 uncertain significance, 32 conflicting classifications of pathogenicity, 30 pathogenic/likely pathogenic, 30 pathogenic, 13 likely pathogenic, 10 benign/likely benign, 5 likely benign, 3 benign, 3 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
194774	NM_017950.4(CCDC40):c.2824_2825insCTGT (p.Arg942fs)	CCDC40	Pathogenic	criteria provided, multiple submitters, no conflicts
488402	NM_017950.4(CCDC40):c.1989+1G>A	CCDC40	Pathogenic	criteria provided, single submitter
263	NM_178452.6(DNAAF1):c.1349dup (p.Pro451fs)	DNAAF1	Pathogenic	criteria provided, single submitter
267	NM_178452.6(DNAAF1):c.524T>G (p.Leu175Arg)	DNAAF1	Pathogenic	no assertion criteria provided
208996	NM_012472.6(DNAAF11):c.630del (p.Trp210fs)	DNAAF11	Pathogenic	criteria provided, multiple submitters, no conflicts
208847	NM_018139.3(DNAAF2):c.1199_1214dup (p.Gly406fs)	DNAAF2	Pathogenic	no assertion criteria provided
529	NM_018139.3(DNAAF2):c.23C>A (p.Ser8Ter)	DNAAF2	Pathogenic	no assertion criteria provided
1452056	NM_001277115.2(DNAH11):c.3020T>G (p.Leu1007Ter)	DNAH11	Pathogenic	criteria provided, single submitter
3776911	NM_001277115.2(DNAH11):c.2709del (p.Trp904fs)	DNAH11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208992	NM_001369.3(DNAH5):c.4348C>T (p.Gln1450Ter)	DNAH5	Pathogenic	criteria provided, multiple submitters, no conflicts
488401	NM_001369.3(DNAH5):c.6000C>A (p.Tyr2000Ter)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
488403	NM_001369.3(DNAH5):c.4530del (p.Asn1511fs)	DNAH5	Pathogenic	criteria provided, single submitter
1066781	NM_012144.4(DNAI1):c.1818+1G>T	DNAI1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066912	NM_012144.4(DNAI1):c.1063+1G>A	DNAI1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071575	NM_012144.4(DNAI1):c.178dup (p.Ala60fs)	DNAI1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1184556	NM_012144.4(DNAI1):c.565_566del (p.Leu188_Thr189insTer)	DNAI1	Pathogenic	criteria provided, multiple submitters, no conflicts
1343809	NM_012144.4(DNAI1):c.1871del (p.Pro624fs)	DNAI1	Pathogenic	criteria provided, single submitter
1364355	NM_012144.4(DNAI1):c.598C>T (p.Gln200Ter)	DNAI1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1377462	NM_012144.4(DNAI1):c.1348_1352del (p.Asn450fs)	DNAI1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1439851	NM_012144.4(DNAI1):c.530T>A (p.Leu177Ter)	DNAI1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1514662	NM_012144.4(DNAI1):c.180+1G>A	DNAI1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1777972	NM_012144.4(DNAI1):c.1684G>A (p.Asp562Asn)	DNAI1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1903913	NM_012144.4(DNAI1):c.1019G>A (p.Trp340Ter)	DNAI1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1983133	NM_012144.4(DNAI1):c.397G>T (p.Glu133Ter)	DNAI1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2148317	NM_012144.4(DNAI1):c.1644del (p.Ser547_Trp548insTer)	DNAI1	Pathogenic	criteria provided, multiple submitters, no conflicts
2172661	NM_012144.4(DNAI1):c.885_886dup (p.Asp296fs)	DNAI1	Pathogenic	criteria provided, multiple submitters, no conflicts
228334	NM_012144.4(DNAI1):c.336del (p.Asp114fs)	DNAI1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
240853	NM_012144.4(DNAI1):c.1307G>A (p.Trp436Ter)	DNAI1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
240854	NM_012144.4(DNAI1):c.1644G>A (p.Trp548Ter)	DNAI1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
260201	NM_012144.4(DNAI1):c.180G>A (p.Ala60=)	DNAI1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 20 · 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
DNAI1	Strong	Autosomal recessive	primary ciliary dyskinesia 1	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNAI1	Orphanet:244	Primary ciliary dyskinesia
SPAG1	Orphanet:244	Primary ciliary dyskinesia
RSPH1	Orphanet:244	Primary ciliary dyskinesia
DNAAF11	Orphanet:244	Primary ciliary dyskinesia
ZMYND10	Orphanet:244	Primary ciliary dyskinesia
DNAAF2	Orphanet:244	Primary ciliary dyskinesia
RSPH4A	Orphanet:244	Primary ciliary dyskinesia
DNAL1	Orphanet:244	Primary ciliary dyskinesia
DRC1	Orphanet:244	Primary ciliary dyskinesia
DRC1	Orphanet:276234	Non-syndromic male infertility due to sperm motility disorder
LRRC56	Orphanet:244	Primary ciliary dyskinesia
ODAD2	Orphanet:244	Primary ciliary dyskinesia
CCDC40	Orphanet:244	Primary ciliary dyskinesia
ODAD1	Orphanet:244	Primary ciliary dyskinesia
ODAD3	Orphanet:244	Primary ciliary dyskinesia
DNAH1	Orphanet:244	Primary ciliary dyskinesia
DNAH1	Orphanet:276234	Non-syndromic male infertility due to sperm motility disorder
DNAH11	Orphanet:244	Primary ciliary dyskinesia
DNAH5	Orphanet:244	Primary ciliary dyskinesia
DNAAF1	Orphanet:244	Primary ciliary dyskinesia

Cohort genes → proteins

19 cohort genes, 19 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	19

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DNAI1	HGNC:2954	ENSG00000122735	Q9UI46	Dynein axonemal intermediate chain 1	gencc,clinvar
SPAG1	HGNC:11212	ENSG00000104450	Q07617	Sperm-associated antigen 1	clinvar
RSPH1	HGNC:12371	ENSG00000160188	Q8WYR4	Radial spoke head 1 homolog	clinvar
DNAAF11	HGNC:16725	ENSG00000129295	Q86X45	Dynein axonemal assembly factor 11	clinvar
ZMYND10	HGNC:19412	ENSG00000004838	O75800	Zinc finger MYND domain-containing protein 10	clinvar
DNAAF2	HGNC:20188	ENSG00000165506	Q9NVR5	Protein kintoun	clinvar
RSPH4A	HGNC:21558	ENSG00000111834	Q5TD94	Radial spoke head protein 4 homolog A	clinvar
DNAL1	HGNC:23247	ENSG00000119661	Q4LDG9	Dynein axonemal light chain 1	clinvar
DRC1	HGNC:24245	ENSG00000157856	Q96MC2	Dynein regulatory complex protein 1	clinvar
LRRC56	HGNC:25430	ENSG00000161328	Q8IYG6	Leucine-rich repeat-containing protein 56	clinvar
ODAD2	HGNC:25583	ENSG00000169126	Q5T2S8	Outer dynein arm-docking complex subunit 2	clinvar
CCDC40	HGNC:26090	ENSG00000141519	Q4G0X9	Coiled-coil domain-containing protein 40	clinvar
ODAD1	HGNC:26560	ENSG00000105479	Q96M63	Outer dynein arm-docking complex subunit 1	clinvar
ODAD3	HGNC:28303	ENSG00000198003	A5D8V7	Outer dynein arm-docking complex subunit 3	clinvar
DNAH1	HGNC:2940	ENSG00000114841	Q9P2D7	Dynein axonemal heavy chain 1	clinvar
DNAH11	HGNC:2942	ENSG00000105877	Q96DT5	Dynein axonemal heavy chain 11	clinvar
DNAH5	HGNC:2950	ENSG00000039139	Q8TE73	Dynein axonemal heavy chain 5	clinvar
DNAAF1	HGNC:30539	ENSG00000154099	Q8NEP3	Dynein axonemal assembly factor 1	clinvar
POLR2K	HGNC:9198	ENSG00000147669	P53803	DNA-directed RNA polymerases I, II, and III subunit RPABC4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNAI1	Dynein axonemal intermediate chain 1	Component of dynein, a family of motor proteins essential for movement along microtubules.
SPAG1	Sperm-associated antigen 1	May play a role in the cytoplasmic assembly of the ciliary dynein arms.
RSPH1	Radial spoke head 1 homolog	Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.
DNAAF11	Dynein axonemal assembly factor 11	Involved in dynein arm assembly, is important for expression and transporting outer dynein arm (ODA) proteins from the cytoplasm to the cilia.
ZMYND10	Zinc finger MYND domain-containing protein 10	Plays a role in axonemal structure organization and motility.
DNAAF2	Protein kintoun	Required for cytoplasmic pre-assembly of axonemal dyneins, thereby playing a central role in motility in cilia and flagella.
RSPH4A	Radial spoke head protein 4 homolog A	Component of the axonemal radial spoke head which plays an important role in ciliary motility.
DNAL1	Dynein axonemal light chain 1	Part of the multisubunit axonemal ATPase complexes that generate the force for cilia motility and govern beat frequency.
DRC1	Dynein regulatory complex protein 1	Component of the nexin-dynein regulatory complex (N-DRC) a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes.
LRRC56	Leucine-rich repeat-containing protein 56	Required for the assembly of dynein arms.
ODAD2	Outer dynein arm-docking complex subunit 2	Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule.
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.
ODAD1	Outer dynein arm-docking complex subunit 1	Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule.
ODAD3	Outer dynein arm-docking complex subunit 3	Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule.
DNAH1	Dynein axonemal heavy chain 1	Force generating protein of cilia required for sperm flagellum motility.
DNAH11	Dynein axonemal heavy chain 11	Force generating protein required for cilia beating in respiratory epithelia.
DNAH5	Dynein axonemal heavy chain 5	Force generating protein of respiratory cilia.
DNAAF1	Dynein axonemal assembly factor 1	Cilium-specific protein required for the stability of the ciliary architecture.
POLR2K	DNA-directed RNA polymerases I, II, and III subunit RPABC4	DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 17 · 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	17	1.6×	0.006
Scaffold/PPI	1	0.9×	0.914
Transcription factor	1	0.4×	0.914

Per-gene assignment

Symbol	Family	Druggable?	InterPro (top 3)
DNAI1	Scaffold/PPI	no	WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
SPAG1	Other/Unknown	no	TPR-like_helical_dom_sf, TPR_rpt, RPAP3-like_C
RSPH1	Other/Unknown	no	MORN
DNAAF11	Other/Unknown	no	Leu-rich_rpt, U2A’_phosphoprotein32A_C, CS_dom
ZMYND10	Transcription factor	no	Znf_MYND, UCP037948_Znf-MYND, ZMYND10
DNAAF2	Other/Unknown	no	PIH1_N, Kintoun, PIH1D1/2/3_CS-like
RSPH4A	Other/Unknown	no	Radial_spoke
DNAL1	Other/Unknown	no	Leu-rich_rpt, Leu-rich_rpt_4, LRR_dom_sf
DRC1	Other/Unknown	no	DRC1_C, DRC1/2_N, DRC1/DRC2
LRRC56	Other/Unknown	no	Leu-rich_rpt, Leu-rich_rpt_4, LRR_dom_sf
ODAD2	Other/Unknown	no	Armadillo, ARM-like, ARM-type_fold
CCDC40	Other/Unknown	no	CCDC40
ODAD1	Other/Unknown	no	ODAD1_CC, ODA-DC/CCD
ODAD3	Other/Unknown	no	ODAD3
DNAH1	Other/Unknown	no	Dhc_D6_P-loop, Dhc_linker, Dhc_D4
DNAH11	Other/Unknown	no	AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
DNAH5	Other/Unknown	no	AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
DNAAF1	Other/Unknown	no	Leu-rich_rpt, LRR_dom_sf, Cilia_flagella_integrity
POLR2K	Other/Unknown	no	RNAP_P/RPABC4, RPABC4/Spt4, RPABC4

Expression context

Cohort genes with no expression data: 0.

19 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)	19
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	14
right uterine tube	14
bronchus	6
epithelium of bronchus	4
left testis	3
oviduct epithelium	3
right testis	2
mucosa of sigmoid colon	1
palpebral conjunctiva	1
oocyte	1
mucosa of paranasal sinus	1
olfactory segment of nasal mucosa	1
buccal mucosa cell	1
sperm	1
sural nerve	1
calcaneal tendon	1
islet of Langerhans	1
popliteal artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNAI1	170	broad	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus
SPAG1	249	ubiquitous	marker	bronchial epithelial cell, mucosa of sigmoid colon, palpebral conjunctiva
RSPH1	200	broad	marker	bronchial epithelial cell, bronchus, right uterine tube
DNAAF11	219	broad	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus
ZMYND10	175	broad	marker	right uterine tube, left testis, right testis
DNAAF2	273	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, oocyte
RSPH4A	164	tissue_specific	marker	right uterine tube, olfactory segment of nasal mucosa, mucosa of paranasal sinus
DNAL1	224	ubiquitous	marker	buccal mucosa cell, oviduct epithelium, left testis
DRC1	141	broad	marker	right uterine tube, bronchial epithelial cell, bronchus
LRRC56	129	broad	marker	right uterine tube, right testis, left testis
ODAD2	173	broad	marker	bronchial epithelial cell, right uterine tube, sperm
CCDC40	184	ubiquitous	marker	right uterine tube, bronchial epithelial cell, sural nerve
ODAD1	174	broad	marker	oviduct epithelium, right uterine tube, bronchial epithelial cell
ODAD3	177	broad	marker	bronchial epithelial cell, bronchus, right uterine tube
DNAH1	183	tissue_specific	marker	right uterine tube, bronchial epithelial cell, bronchus
DNAH11	163	broad	marker	right uterine tube, bronchial epithelial cell, bronchus
DNAH5	184	broad	marker	bronchial epithelial cell, bronchus, oviduct epithelium
DNAAF1	201	broad	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus
POLR2K	295	ubiquitous	marker	islet of Langerhans, calcaneal tendon, popliteal artery

Protein interactions among cohort

Intra-cohort edges: 70.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
POLR2K	2,950
ODAD2	2,251
SPAG1	2,175
DNAH5	1,834
ODAD3	1,817
DNAH1	1,699
DNAH11	1,666
RSPH4A	1,637
CCDC40	1,527
RSPH1	1,431

Intra-cohort edges

A	B	Sources
CCDC40	DNAAF1	string_interaction
CCDC40	DNAAF11	string_interaction
CCDC40	DNAH1	string_interaction
CCDC40	DNAH11	string_interaction
CCDC40	DNAH5	string_interaction
CCDC40	DNAI1	string_interaction
CCDC40	DRC1	string_interaction
CCDC40	ODAD1	string_interaction
CCDC40	ODAD2	string_interaction
CCDC40	ODAD3	string_interaction
CCDC40	RSPH1	string_interaction
CCDC40	RSPH4A	string_interaction
CCDC40	ZMYND10	string_interaction
DNAAF1	DNAAF2	string_interaction
DNAAF1	DNAH11	string_interaction
DNAAF1	DNAH5	string_interaction
DNAAF1	DNAI1	string_interaction
DNAAF1	DRC1	string_interaction
DNAAF1	RSPH4A	string_interaction
DNAAF1	SPAG1	string_interaction
DNAAF1	ZMYND10	string_interaction
DNAAF11	DNAAF2	string_interaction
DNAAF11	DNAH11	string_interaction
DNAAF11	DNAI1	string_interaction
DNAAF11	ODAD1	string_interaction
DNAAF11	ODAD2	string_interaction
DNAAF11	SPAG1	string_interaction
DNAAF11	ZMYND10	string_interaction
DNAAF2	DNAH11	string_interaction
DNAAF2	DNAH5	string_interaction
DNAAF2	DNAI1	string_interaction
DNAAF2	RSPH4A	string_interaction
DNAH1	ODAD1	string_interaction
DNAH11	DNAI1	string_interaction
DNAH11	DRC1	string_interaction
DNAH11	ODAD1	string_interaction
DNAH11	ODAD2	string_interaction
DNAH11	RSPH1	string_interaction
DNAH11	RSPH4A	string_interaction
DNAH5	DNAI1	string_interaction
DNAH5	DNAL1	string_interaction
DNAH5	ODAD1	string_interaction
DNAH5	ODAD2	string_interaction
DNAH5	ODAD3	string_interaction
DNAH5	RSPH1	string_interaction
DNAH5	RSPH4A	string_interaction
DNAI1	ODAD1	string_interaction
DNAI1	ODAD2	string_interaction
DNAI1	ODAD3	string_interaction
DNAI1	RSPH4A	string_interaction

Structural data

PDB: 14 · AlphaFold-only: 5 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
POLR2K	P53803	57
SPAG1	Q07617	4
ZMYND10	O75800	2
DNAH1	Q9P2D7	2
DNAI1	Q9UI46	1
RSPH1	Q8WYR4	1
RSPH4A	Q5TD94	1
DNAL1	Q4LDG9	1
DRC1	Q96MC2	1
ODAD2	Q5T2S8	1
CCDC40	Q4G0X9	1
ODAD1	Q96M63	1
ODAD3	A5D8V7	1
DNAH5	Q8TE73	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DNAAF11	Q86X45	74.44
DNAAF2	Q9NVR5	65.57
DNAAF1	Q8NEP3	61.56
LRRC56	Q8IYG6	56.07
DNAH11	Q96DT5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 97. Enrichment computed across 19 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
FGFR2 mutant receptor activation	1	761.3×	0.008	POLR2K
RNA Polymerase III Chain Elongation	1	634.4×	0.008	POLR2K
Signaling by FGFR2 IIIa TM	1	601.0×	0.008	POLR2K
Abortive elongation of HIV-1 transcript in the absence of Tat	1	496.5×	0.008	POLR2K
RNA Polymerase III Transcription Termination	1	496.5×	0.008	POLR2K
MicroRNA (miRNA) biogenesis	1	456.8×	0.008	POLR2K
Activation of HOX genes during differentiation	1	439.2×	0.008	POLR2K
Signaling by FGFR in disease	1	423.0×	0.008	POLR2K
FGFR2 alternative splicing	1	423.0×	0.008	POLR2K
RNA Polymerase III Transcription Initiation From Type 2 Promoter	1	423.0×	0.008	POLR2K
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	1	407.9×	0.008	POLR2K
Signaling by FGFR2	1	407.9×	0.008	POLR2K
RNA Polymerase III Transcription Initiation From Type 1 Promoter	1	407.9×	0.008	POLR2K
RNA Polymerase III Transcription Initiation From Type 3 Promoter	1	407.9×	0.008	POLR2K
RNA Pol II CTD phosphorylation and interaction with CE	1	407.9×	0.008	POLR2K
PIWI-interacting RNA (piRNA) biogenesis	1	393.8×	0.008	POLR2K
mRNA Capping	1	380.7×	0.008	POLR2K
Telomere Maintenance	1	368.4×	0.008	POLR2K
Pausing and recovery of Tat-mediated HIV elongation	1	368.4×	0.008	POLR2K
Tat-mediated HIV elongation arrest and recovery	1	368.4×	0.008	POLR2K
Gene Silencing by RNA	1	356.9×	0.008	POLR2K
HIV elongation arrest and recovery	1	346.1×	0.008	POLR2K
Pausing and recovery of HIV elongation	1	346.1×	0.008	POLR2K
Signaling by FGFR	1	346.1×	0.008	POLR2K
Positive epigenetic regulation of rRNA expression	1	346.1×	0.008	POLR2K
Formation of the Early Elongation Complex	1	335.9×	0.008	POLR2K
Formation of the HIV-1 Early Elongation Complex	1	335.9×	0.008	POLR2K
HIV Transcription Elongation	1	335.9×	0.008	POLR2K
RNA Polymerase III Transcription Initiation	1	335.9×	0.008	POLR2K
RNA Polymerase I Transcription Termination	1	326.3×	0.008	POLR2K

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 19 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
outer dynein arm assembly	10	385.6×	1e-23	DNAI1, DNAAF11, ZMYND10, DNAAF2, DNAL1, ODAD2, ODAD1, ODAD3 (+2 more)
cilium movement	10	206.3×	1e-20	DNAI1, DNAAF11, ZMYND10, RSPH4A, ODAD2, CCDC40, ODAD1, ODAD3 (+2 more)
epithelial cilium movement involved in extracellular fluid movement	7	282.2×	2e-15	DNAI1, DNAAF11, DNAAF2, RSPH4A, CCDC40, DNAH1, DNAH5
axonemal dynein complex assembly	6	332.6×	1e-13	SPAG1, DNAAF11, DNAAF2, DRC1, CCDC40, DNAAF1
inner dynein arm assembly	6	280.1×	3e-13	DNAAF11, ZMYND10, DNAAF2, CCDC40, DNAH1, DNAAF1
epithelial cilium movement involved in determination of left/right asymmetry	5	341.1×	1e-11	DNAAF11, CCDC40, ODAD3, DNAH11, DNAAF1
regulation of cilium beat frequency	4	443.5×	6e-10	ODAD2, CCDC40, DNAH11, DNAAF1
determination of left/right symmetry	6	80.6×	6e-10	DNAI1, DRC1, ODAD2, ODAD3, DNAH11, DNAH5
flagellated sperm motility	7	43.1×	9e-10	DNAI1, DNAAF11, CCDC40, ODAD3, DNAH1, DNAH11, DNAH5
motile cilium assembly	4	122.3×	2e-07	DNAAF11, ZMYND10, CCDC40, DNAAF1
axoneme assembly	4	114.4×	2e-07	RSPH1, RSPH4A, CCDC40, DNAAF1
cilium-dependent cell motility	3	221.7×	1e-06	DNAAF2, DRC1, DNAH1
cilium movement involved in cell motility	3	106.4×	1e-05	RSPH4A, DNAH11, DNAH5
establishment of localization in cell	4	33.8×	2e-05	DNAAF11, DNAAF2, RSPH4A, DNAH5
determination of pancreatic left/right asymmetry	2	354.8×	5e-05	CCDC40, DNAAF1
protein localization to motile cilium	2	354.8×	5e-05	DNAAF11, DNAH11
protein localization to cilium	3	63.4×	5e-05	DNAAF11, ZMYND10, CCDC40
determination of digestive tract left/right asymmetry	2	295.6×	6e-05	CCDC40, DNAAF1
determination of liver left/right asymmetry	2	295.6×	6e-05	CCDC40, DNAAF1
heart development	4	16.6×	3e-04	DNAI1, DRC1, ODAD2, DNAH5
single fertilization	3	28.9×	4e-04	SPAG1, DRC1, ODAD3
cerebrospinal fluid circulation	2	93.4×	6e-04	DNAAF11, ODAD3
maintenance of ciliary planar beating movement pattern	1	887.0×	0.003	RSPH4A
positive regulation of motile cilium assembly	1	887.0×	0.003	ZMYND10
determination of left/right asymmetry in nervous system	1	443.5×	0.005	DNAH11
heart looping	2	28.2×	0.005	CCDC40, DNAAF1
radial spoke assembly	1	295.6×	0.008	RSPH4A
lung development	2	20.9×	0.009	CCDC40, DNAAF1
regulation of cilium movement	1	221.7×	0.009	DRC1
regulation of transcription by RNA polymerase I	1	221.7×	0.009	POLR2K

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 19

Druggability breadth: 0 of 19 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
DNAI1	0	0
SPAG1	0	0
RSPH1	0	0
DNAAF11	0	0
ZMYND10	0	0
DNAAF2	0	0
RSPH4A	0	0
DNAL1	0	0
DRC1	0	0
LRRC56	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 19; 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	19	DNAI1, SPAG1, RSPH1, DNAAF11, ZMYND10, DNAAF2, RSPH4A, DNAL1, DRC1, LRRC56 (+9 more)

Undrugged target profiles

19 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
DNAI1	0	—
SPAG1	0	—
RSPH1	0	—
DNAAF11	0	—
ZMYND10	0	—
DNAAF2	0	—
RSPH4A	0	—
DNAL1	0	—
DRC1	0	—
LRRC56	0	—
ODAD2	0	—
CCDC40	0	—
ODAD1	0	—
ODAD3	0	—
DNAH1	0	—
DNAH11	0	—
DNAH5	0	—
DNAAF1	0	—
POLR2K	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: DNAI1, SPAG1, RSPH1, DNAAF11, ZMYND10, DNAAF2, RSPH4A, DNAL1, DRC1, LRRC56, ODAD2, CCDC40, ODAD1, ODAD3, DNAH1, DNAH11, DNAH5, DNAAF1, POLR2K