Primary ciliary dyskinesia 3

Summary

Primary ciliary dyskinesia 3 (MONDO:0012085) is a disease caused by DNAH5 (GenCC Strong), with 12 cohort genes.

At a glance

• Causal gene: DNAH5 (GenCC Strong)
• Cohort genes: 12
• ClinVar variants: 1,066

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 3
Mondo ID	MONDO:0012085
MeSH	C535278
OMIM	608644
DOID	DOID:0110599
NCIT	C172392
UMLS	C1837618
MedGen	325210
GARD	0015436
Is cancer (heuristic)	no

Also known as: CILD3 · ciliary dyskinesia, primary, 3 · ciliary dyskinesia, primary, type 3 · DNAH5 primary ciliary dyskinesia · primary ciliary dyskinesia 3 · primary ciliary dyskinesia caused by mutation in DNAH5 · primary ciliary dyskinesia type 3

Data availability: 1,066 ClinVar variants · 3 GenCC gene-disease records · 3 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › primary ciliary dyskinesia › primary ciliary dyskinesia 3

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 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

600 retrieved; paginated sample, class counts are floors:

207 likely pathogenic, 114 conflicting classifications of pathogenicity, 80 benign, 76 uncertain significance, 50 pathogenic/likely pathogenic, 33 benign/likely benign, 26 pathogenic, 14 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3075733	NM_001369.3:c.[13486C>T];[13194_13197del]		Pathogenic	criteria provided, single submitter
2505511	NM_017950.4(CCDC40):c.967C>T (p.Gln323Ter)	CCDC40	Pathogenic	no assertion criteria provided
1012297	NM_001369.3(DNAH5):c.1090del (p.Leu364fs)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1012301	NM_001369.3(DNAH5):c.9033del (p.Phe3011fs)	DNAH5	Pathogenic	criteria provided, single submitter
1012302	NM_001369.3(DNAH5):c.8806del (p.Val2936fs)	DNAH5	Pathogenic	criteria provided, single submitter
1016659	NM_001369.3(DNAH5):c.6088T>G (p.Cys2030Gly)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1027908	NM_001369.3(DNAH5):c.12907C>T (p.Gln4303Ter)	DNAH5	Pathogenic	criteria provided, single submitter
1066064	NM_001369.3(DNAH5):c.13774C>T (p.Arg4592Ter)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070301	NM_001369.3(DNAH5):c.5883-1G>A	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070752	NM_001369.3(DNAH5):c.376del (p.Val126fs)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072564	NM_001369.3(DNAH5):c.10825C>T (p.Gln3609Ter)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073312	NM_001369.3(DNAH5):c.7407+1G>A	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075247	NM_001369.3(DNAH5):c.1351_1355del (p.Gln451fs)	DNAH5	Pathogenic	criteria provided, multiple submitters, no conflicts
1075787	NM_001369.3(DNAH5):c.4084C>T (p.Gln1362Ter)	DNAH5	Pathogenic	criteria provided, multiple submitters, no conflicts
1184500	NM_001369.3(DNAH5):c.5890_5894dup (p.Leu1966fs)	DNAH5	Pathogenic	criteria provided, multiple submitters, no conflicts
1335571	NM_001369.3(DNAH5):c.8032C>T (p.Gln2678Ter)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1344588	NM_001369.3(DNAH5):c.12009G>A (p.Trp4003Ter)	DNAH5	Pathogenic	criteria provided, multiple submitters, no conflicts
1344886	NM_001369.3(DNAH5):c.11571-1G>A	DNAH5	Pathogenic	criteria provided, multiple submitters, no conflicts
1344889	NM_001369.3(DNAH5):c.12397G>T (p.Glu4133Ter)	DNAH5	Pathogenic	criteria provided, multiple submitters, no conflicts
1361077	NM_001369.3(DNAH5):c.7369C>T (p.Gln2457Ter)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1366452	NM_001369.3(DNAH5):c.3598+1G>A	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1371439	NM_001369.3(DNAH5):c.11658_11668del (p.Leu3887fs)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1381051	NM_001369.3(DNAH5):c.11935dup (p.Glu3979fs)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1444914	NM_001369.3(DNAH5):c.3675C>G (p.Tyr1225Ter)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451397	NM_001369.3(DNAH5):c.6442C>T (p.Gln2148Ter)	DNAH5	Pathogenic	criteria provided, single submitter
1452767	NM_001369.3(DNAH5):c.5999dup (p.Tyr2000Ter)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453260	NM_001369.3(DNAH5):c.4314del (p.Asn1438fs)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453634	NM_001369.3(DNAH5):c.9990del (p.Gln3331fs)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453797	NM_001369.3(DNAH5):c.958_959dup (p.Lys322fs)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454439	NM_001369.3(DNAH5):c.9975C>A (p.Cys3325Ter)	DNAH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 15 · 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
DNAH5	Strong	Autosomal recessive	primary ciliary dyskinesia 3	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNAH5	Orphanet:244	Primary ciliary dyskinesia
BACH2	Orphanet:714472	Inflammatory bowel disease-autoimmunity-sinopulmonary infections-lymphadenopathy syndrome
DNAH7	Orphanet:244	Primary ciliary dyskinesia
CREBBP	Orphanet:353277	Rubinstein-Taybi syndrome due to CREBBP mutations
CREBBP	Orphanet:353281	Rubinstein-Taybi syndrome due to 16p13.3 microdeletion
CREBBP	Orphanet:370026	Acute myeloid leukemia with t(8;16)(p11;p13) translocation
CREBBP	Orphanet:592574	Menke-Hennekam syndrome
GAS2L2	Orphanet:244	Primary ciliary dyskinesia
CCDC40	Orphanet:244	Primary ciliary dyskinesia
DNAH11	Orphanet:244	Primary ciliary dyskinesia
DNAH9	Orphanet:101063	Situs inversus totalis
DNAH9	Orphanet:157769	Situs ambiguus
DNAH9	Orphanet:244	Primary ciliary dyskinesia
MCIDAS	Orphanet:244	Primary ciliary dyskinesia
NFKB1	Orphanet:696874	NFKB1-related immune dysregulation

Cohort genes → proteins

12 cohort genes, 11 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	12

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DNAH5	HGNC:2950	ENSG00000039139	Q8TE73	Dynein axonemal heavy chain 5	gencc,clinvar
BACH2	HGNC:14078	ENSG00000112182	Q9BYV9	Transcription regulator protein BACH2	clinvar
DNAH7	HGNC:18661	ENSG00000118997	Q8WXX0	Dynein axonemal heavy chain 7	clinvar
CREBBP	HGNC:2348	ENSG00000005339	Q92793	CREB-binding protein	clinvar
GAS2L2	HGNC:24846	ENSG00000270765	Q8NHY3	GAS2-like protein 2	clinvar
CCDC40	HGNC:26090	ENSG00000141519	Q4G0X9	Coiled-coil domain-containing protein 40	clinvar
DNAH11	HGNC:2942	ENSG00000105877	Q96DT5	Dynein axonemal heavy chain 11	clinvar
DNAH9	HGNC:2953	ENSG00000007174	Q9NYC9	Dynein axonemal heavy chain 9	clinvar
MPEG1	HGNC:29619	ENSG00000197629	Q2M385	Macrophage-expressed gene 1 protein	clinvar
MCIDAS	HGNC:40050	ENSG00000234602	D6RGH6	Multicilin	clinvar
DNAH5-AS1	HGNC:40187	ENSG00000251423		DNAH5 antisense RNA 1	clinvar
NFKB1	HGNC:7794	ENSG00000109320	P19838	Nuclear factor NF-kappa-B p105 subunit	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNAH5	Dynein axonemal heavy chain 5	Force generating protein of respiratory cilia.
BACH2	Transcription regulator protein BACH2	Transcriptional regulator that acts as a repressor or activator.
DNAH7	Dynein axonemal heavy chain 7	Force generating protein that plays an important role in respiratory cilia and sperm flagella beating.
CREBBP	CREB-binding protein	Acetylates histones, giving a specific tag for transcriptional activation.
GAS2L2	GAS2-like protein 2	Involved in the cross-linking of microtubules and microfilaments.
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.
DNAH11	Dynein axonemal heavy chain 11	Force generating protein required for cilia beating in respiratory epithelia.
DNAH9	Dynein axonemal heavy chain 9	Force generating protein required for cilia beating in respiratory epithelia.
MPEG1	Macrophage-expressed gene 1 protein	Pore-forming protein involved in both innate and adaptive immunity.
MCIDAS	Multicilin	Transcription regulator specifically required for multiciliate cell differentiation.
NFKB1	Nuclear factor NF-kappa-B p105 subunit	NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as infl…

Protein-family classification

Druggable: 1 · Difficult: 3 · Unknown: 8 · Druggable fraction: 0.08

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
Complement	1	22.3×	0.132
Transcription factor	3	2.1×	0.255
Other/Unknown	8	1.2×	0.325

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNAH5	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
BACH2	Transcription factor	no		BTB/POZ_dom, bZIP_Maf, bZIP
DNAH7	Other/Unknown	no		EF_hand_dom, AAA+_ATPase, Dhc_D6_P-loop
CREBBP	Transcription factor	no	2.3.1.48	Znf_TAZ, Znf_ZZ, Bromodomain
GAS2L2	Other/Unknown	no		CH_dom, GAR_dom, GAR_dom_sf
CCDC40	Other/Unknown	no		CCDC40
DNAH11	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
DNAH9	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
MPEG1	Complement	yes		MACPF, MPEG1
MCIDAS	Other/Unknown	no		Geminin/Multicilin
DNAH5-AS1	Other/Unknown	no
NFKB1	Transcription factor	no		NFkB/Dor, Death_dom, Ankyrin_rpt

Expression context

Cohort genes with no expression data: 0.

11 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)	12
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	6
right uterine tube	5
sural nerve	3
bronchus	2
epithelium of bronchus	2
olfactory segment of nasal mucosa	2
oviduct epithelium	1
cortical plate	1
epithelium of nasopharynx	1
amniotic fluid	1
tibia	1
ileal mucosa	1
leukocyte	1
monocyte	1
male germ line stem cell (sensu Vertebrata) in testis	1
right lobe of thyroid gland	1
cortex of kidney	1
esophagogastric junction muscularis propria	1
tibial nerve	1
calcaneal tendon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNAH5	184	broad	marker	bronchial epithelial cell, bronchus, oviduct epithelium
BACH2	237	ubiquitous	marker	cortical plate, sural nerve, epithelium of nasopharynx
DNAH7	212	broad	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus
CREBBP	297	ubiquitous	marker	sural nerve, tibia, amniotic fluid
GAS2L2	103	tissue_specific	marker	right uterine tube, olfactory segment of nasal mucosa, bronchial epithelial cell
CCDC40	184	ubiquitous	marker	right uterine tube, bronchial epithelial cell, sural nerve
DNAH11	163	broad	marker	right uterine tube, bronchial epithelial cell, bronchus
DNAH9	184	broad	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus
MPEG1	219	broad	marker	monocyte, leukocyte, ileal mucosa
MCIDAS	53		yes	male germ line stem cell (sensu Vertebrata) in testis, olfactory segment of nasal mucosa, right lobe of thyroid gland
DNAH5-AS1	37		marker	cortex of kidney, tibial nerve, esophagogastric junction muscularis propria
NFKB1	252	ubiquitous	marker	endometrium epithelium, cartilage tissue, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 7.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NFKB1	10,484
CREBBP	6,959
BACH2	1,917
DNAH9	1,841
DNAH5	1,834
DNAH11	1,666
DNAH7	1,537
CCDC40	1,527
GAS2L2	1,172
MPEG1	981

Intra-cohort edges

A	B	Sources
CCDC40	DNAH11	string_interaction
CCDC40	DNAH5	string_interaction
CCDC40	DNAH7	string_interaction
CCDC40	DNAH9	string_interaction
CCDC40	MCIDAS	string_interaction
DNAH11	GAS2L2	string_interaction
DNAH9	GAS2L2	string_interaction

Structural data

PDB: 9 · AlphaFold-only: 2 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CREBBP	Q92793	144
NFKB1	P19838	15
MPEG1	Q2M385	5
BACH2	Q9BYV9	2
DNAH7	Q8WXX0	2
DNAH5	Q8TE73	1
CCDC40	Q4G0X9	1
DNAH9	Q9NYC9	1
MCIDAS	D6RGH6	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GAS2L2	Q8NHY3	56.13
DNAH11	Q96DT5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 150. Enrichment computed across 12 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Regulation of NFE2L2 gene expression	2	1427.5×	6e-05	CREBBP, NFKB1
CD209 (DC-SIGN) signaling	2	519.1×	3e-04	CREBBP, NFKB1
Transcriptional regulation of white adipocyte differentiation	2	129.8×	0.003	CREBBP, NFKB1
Regulation of PD-L1(CD274) transcription	2	108.8×	0.003	CREBBP, NFKB1
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production	1	1142.0×	0.013	CREBBP
NFE2L2 regulating inflammation associated genes	1	1142.0×	0.013	CREBBP
NFE2L2 regulating ER-stress associated genes	1	1142.0×	0.013	CREBBP
CLEC7A/inflammasome pathway	1	951.7×	0.013	NFKB1
DEx/H-box helicases activate type I IFN and inflammatory cytokines production	1	815.7×	0.013	NFKB1
IkBA variant leads to EDA-ID	1	815.7×	0.013	NFKB1
RUNX1 regulates transcription of genes involved in differentiation of myeloid cells	1	713.8×	0.013	CREBBP
NFE2L2 regulates pentose phosphate pathway genes	1	713.8×	0.013	CREBBP
NFE2L2 regulating MDR associated enzymes	1	713.8×	0.013	CREBBP
Interleukin-1 processing	1	634.4×	0.013	NFKB1
Regulation of FOXO transcriptional activity by acetylation	1	571.0×	0.013	CREBBP
Regulated proteolysis of p75NTR	1	519.1×	0.013	NFKB1
Regulation of gene expression by Hypoxia-inducible Factor	1	475.8×	0.013	CREBBP
Activation of the TFAP2 (AP-2) family of transcription factors	1	475.8×	0.013	CREBBP
NFE2L2 regulating tumorigenic genes	1	475.8×	0.013	CREBBP
Cellular response to hypoxia	1	439.2×	0.013	CREBBP
NF-kB is activated and signals survival	1	439.2×	0.013	NFKB1
Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters	1	439.2×	0.013	CREBBP
RUNX3 regulates NOTCH signaling	1	407.9×	0.013	CREBBP
TRAF3-dependent IRF activation pathway	1	380.7×	0.013	CREBBP
R-HSA-1368082	1	356.9×	0.013	CREBBP
Regulation of beta-cell development	1	356.9×	0.013	CREBBP
Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells	1	356.9×	0.013	CREBBP
MAP3K8 (TPL2)-dependent MAPK1/3 activation	1	356.9×	0.013	NFKB1
FOXO-mediated transcription of cell death genes	1	356.9×	0.013	CREBBP
Maternal to zygotic transition (MZT)	1	356.9×	0.013	CREBBP

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cilium movement involved in cell motility	4	245.1×	1e-07	DNAH5, DNAH7, DNAH11, DNAH9
cilium movement	4	142.5×	7e-07	DNAH5, DNAH7, CCDC40, DNAH9
regulation of cilium beat frequency	2	383.0×	4e-04	CCDC40, DNAH11
antibacterial innate immune response	2	278.6×	6e-04	MPEG1, NFKB1
epithelial cilium movement involved in determination of left/right asymmetry	2	235.7×	7e-04	CCDC40, DNAH11
inner dynein arm assembly	2	161.3×	0.001	DNAH7, CCDC40
epithelial cilium movement involved in extracellular fluid movement	2	139.3×	0.001	DNAH5, CCDC40
flagellated sperm motility	3	31.9×	0.001	DNAH5, CCDC40, DNAH11
motile cilium assembly	2	105.7×	0.002	CCDC40, MCIDAS
canonical NF-kappaB signal transduction	2	66.6×	0.004	CREBBP, NFKB1
dendritic cell antigen processing and presentation	1	1532.0×	0.006	MPEG1
antigen processing and presentation of exogenous peptide antigen	1	1532.0×	0.006	MPEG1
primary adaptive immune response involving T cells and B cells	1	1532.0×	0.006	BACH2
determination of left/right symmetry	2	46.4×	0.006	DNAH5, DNAH11
determination of left/right asymmetry in nervous system	1	766.0×	0.009	DNAH11
protein localization to microtubule plus-end	1	766.0×	0.009	GAS2L2
N-terminal peptidyl-lysine acetylation	1	510.7×	0.012	CREBBP
positive regulation of miRNA metabolic process	1	510.7×	0.012	NFKB1
establishment of localization in cell	2	29.2×	0.012	DNAH5, DNAH9
negative regulation of vitamin D biosynthetic process	1	383.0×	0.014	NFKB1
positive regulation of hyaluronan biosynthetic process	1	383.0×	0.014	NFKB1
determination of pancreatic left/right asymmetry	1	306.4×	0.015	CCDC40
cellular response to dsRNA	1	306.4×	0.015	NFKB1
protein localization to motile cilium	1	306.4×	0.015	DNAH11
mammary gland involution	1	255.3×	0.015	NFKB1
determination of digestive tract left/right asymmetry	1	255.3×	0.015	CCDC40
determination of liver left/right asymmetry	1	255.3×	0.015	CCDC40
centriole assembly	1	255.3×	0.015	MCIDAS
multi-ciliated epithelial cell differentiation	1	255.3×	0.015	MCIDAS
negative regulation of transcription by RNA polymerase I	1	218.9×	0.015	CREBBP

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 10

Druggability breadth: 4 of 12 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CREBBP	COLCHICINE
NFKB1	INDOPROFEN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NFKB1	152	4
CREBBP	13	4
DNAH5	0	0
BACH2	0	0
DNAH7	0	0
GAS2L2	0	0
CCDC40	0	0
DNAH11	0	0
DNAH9	0	0
MPEG1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COLCHICINE	4	CREBBP
ALTRETAMINE	4	CREBBP
INDOPROFEN	4	NFKB1
VAMOROLONE	4	NFKB1
BORTEZOMIB	4	NFKB1
DEXAMETHASONE	4	NFKB1
SULFASALAZINE	4	NFKB1
LEVOSALBUTAMOL	4	NFKB1
CLOTRIMAZOLE	4	NFKB1
GLIPIZIDE	4	NFKB1
SALMETEROL XINAFOATE	4	NFKB1
PHENELZINE	4	NFKB1
SULFAPHENAZOLE	4	NFKB1
AMOXAPINE	4	NFKB1
PROPANTHELINE	4	NFKB1
DECAMETHONIUM	4	NFKB1
NICARDIPINE HYDROCHLORIDE	4	NFKB1
PHENTOLAMINE MESYLATE	4	NFKB1
PHENYLEPHRINE	4	NFKB1
CARISOPRODOL	4	NFKB1
AZELAIC ACID	4	NFKB1
CARBETAPENTANE CITRATE	4	NFKB1
NIALAMIDE	4	NFKB1
EPINEPHRINE BITARTRATE	4	NFKB1
NILUTAMIDE	4	NFKB1
BUDESONIDE	4	NFKB1
ESTRONE	4	NFKB1
METHAPYRILENE	4	NFKB1
PIMOZIDE	4	NFKB1
TRIAMCINOLONE	4	NFKB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CREBBP	687	Binding:644, Functional:43
NFKB1	256	Binding:249, Functional:7
BACH2	3	Binding:3
MPEG1	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CREBBP	2.3.1.48	histone acetyltransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CREBBP	687
NFKB1	256

Pharmacogenomics

Cohort genes with a PharmGKB record: 11; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 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.

Compound	Max phase	Cohort target (bioactivity)
COLCHICINE	4	CREBBP
ALTRETAMINE	4	CREBBP
INDOPROFEN	4	NFKB1
VAMOROLONE	4	NFKB1
BORTEZOMIB	4	NFKB1
DEXAMETHASONE	4	NFKB1
SULFASALAZINE	4	NFKB1
LEVOSALBUTAMOL	4	NFKB1
CLOTRIMAZOLE	4	NFKB1
GLIPIZIDE	4	NFKB1
SALMETEROL XINAFOATE	4	NFKB1
PHENELZINE	4	NFKB1
SULFAPHENAZOLE	4	NFKB1
AMOXAPINE	4	NFKB1
PROPANTHELINE	4	NFKB1
DECAMETHONIUM	4	NFKB1
NICARDIPINE HYDROCHLORIDE	4	NFKB1
PHENTOLAMINE MESYLATE	4	NFKB1
PHENYLEPHRINE	4	NFKB1
CARISOPRODOL	4	NFKB1
AZELAIC ACID	4	NFKB1
CARBETAPENTANE CITRATE	4	NFKB1
NIALAMIDE	4	NFKB1
EPINEPHRINE BITARTRATE	4	NFKB1
NILUTAMIDE	4	NFKB1
BUDESONIDE	4	NFKB1
ESTRONE	4	NFKB1
METHAPYRILENE	4	NFKB1
PIMOZIDE	4	NFKB1
TRIAMCINOLONE	4	NFKB1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	CREBBP, NFKB1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	MPEG1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	9	DNAH5, BACH2, DNAH7, GAS2L2, CCDC40, DNAH11, DNAH9, MCIDAS, DNAH5-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DNAH5	0	—
BACH2	3	—
DNAH7	0	—
GAS2L2	0	—
CCDC40	0	—
DNAH11	0	—
DNAH9	0	—
MPEG1	3	—
MCIDAS	0	—
DNAH5-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.