Ciliary dyskinesia, primary, 37

Summary

Ciliary dyskinesia, primary, 37 (MONDO:0033204) is a disease caused by DNAH1 (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: DNAH1 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 2,387

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ciliary dyskinesia, primary, 37
Mondo ID	MONDO:0033204
OMIM	617577
DOID	DOID:0080266
UMLS	C4539798
MedGen	1615746
GARD	0016239
Is cancer (heuristic)	no

Also known as: CILD37 · ciliary dyskinesia, primary, 37

Data availability: 2,387 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › primary ciliary dyskinesia › ciliary dyskinesia, primary, 37

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 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, 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:

281 uncertain significance, 256 likely benign, 25 benign, 16 pathogenic, 7 benign/likely benign, 7 conflicting classifications of pathogenicity, 6 likely pathogenic, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1033365	NM_015512.5(DNAH1):c.9352C>T (p.Arg3118Ter)	DNAH1	Pathogenic	criteria provided, multiple submitters, no conflicts
1060963	NM_015512.5(DNAH1):c.7066C>T (p.Arg2356Trp)	DNAH1	Pathogenic	criteria provided, single submitter
1068985	NM_015512.5(DNAH1):c.2921_2939dup (p.Arg981fs)	DNAH1	Pathogenic	criteria provided, single submitter
1251942	NM_015512.5(DNAH1):c.3772C>T (p.Gln1258Ter)	DNAH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1401790	NM_015512.5(DNAH1):c.7864C>T (p.Arg2622Ter)	DNAH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1421082	NM_015512.5(DNAH1):c.2005_2014del (p.Gly669fs)	DNAH1	Pathogenic	criteria provided, single submitter
1451711	NM_015512.5(DNAH1):c.3107G>A (p.Trp1036Ter)	DNAH1	Pathogenic	criteria provided, single submitter
1455501	NM_015512.5(DNAH1):c.4167C>A (p.Tyr1389Ter)	DNAH1	Pathogenic	criteria provided, single submitter
1459903	NM_015512.5(DNAH1):c.2602C>T (p.Arg868Ter)	DNAH1	Pathogenic	criteria provided, multiple submitters, no conflicts
1905119	NM_015512.5(DNAH1):c.5547C>A (p.Tyr1849Ter)	DNAH1	Pathogenic	criteria provided, single submitter
1914975	NM_015512.5(DNAH1):c.5308C>T (p.Arg1770Ter)	DNAH1	Pathogenic	criteria provided, single submitter
1965274	NM_015512.5(DNAH1):c.7559C>G (p.Ser2520Ter)	DNAH1	Pathogenic	criteria provided, single submitter
1988199	NM_015512.5(DNAH1):c.526C>T (p.Gln176Ter)	DNAH1	Pathogenic	criteria provided, single submitter
2002471	NM_015512.5(DNAH1):c.2926del (p.Ala976fs)	DNAH1	Pathogenic	criteria provided, single submitter
2021302	NM_015512.5(DNAH1):c.8626-1G>C	DNAH1	Pathogenic	criteria provided, single submitter
2029087	NM_015512.5(DNAH1):c.202_203del (p.Pro68fs)	DNAH1	Pathogenic	criteria provided, single submitter
2033207	NM_015512.5(DNAH1):c.7342del (p.Gln2448fs)	DNAH1	Pathogenic	criteria provided, single submitter
2036895	NM_015512.5(DNAH1):c.3583C>T (p.Gln1195Ter)	DNAH1	Pathogenic	criteria provided, single submitter
1325526	NM_015512.5(DNAH1):c.245del (p.Leu82fs)	DNAH1	Likely pathogenic	criteria provided, single submitter
1483312	NM_015512.5(DNAH1):c.3980+1G>C	DNAH1	Likely pathogenic	criteria provided, single submitter
1504260	NM_015512.5(DNAH1):c.5611-1G>A	DNAH1	Likely pathogenic	criteria provided, single submitter
1973856	NM_015512.5(DNAH1):c.3480+1G>C	DNAH1	Likely pathogenic	criteria provided, single submitter
1993908	NM_015512.5(DNAH1):c.9621+1G>T	DNAH1	Likely pathogenic	criteria provided, single submitter
2027844	NM_015512.5(DNAH1):c.7198+1G>A	DNAH1	Likely pathogenic	criteria provided, single submitter
1301732	NM_015512.5(DNAH1):c.3002G>A (p.Arg1001His)	DNAH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1385471	NM_015512.5(DNAH1):c.11971G>A (p.Val3991Ile)	DNAH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1402087	NM_015512.5(DNAH1):c.10534A>G (p.Asn3512Asp)	DNAH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1416117	NM_015512.5(DNAH1):c.9302A>G (p.Lys3101Arg)	DNAH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1453969	NM_015512.5(DNAH1):c.46C>T (p.Gln16Ter)	DNAH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1489252	NM_015512.5(DNAH1):c.7978G>A (p.Val2660Ile)	DNAH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 4 · 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
DNAH1	Strong	Autosomal recessive	ciliary dyskinesia, primary, 37	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNAH1	Orphanet:244	Primary ciliary dyskinesia
DNAH1	Orphanet:276234	Non-syndromic male infertility due to sperm motility disorder
AFG2A	Orphanet:457351	Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome
DNAH11	Orphanet:244	Primary ciliary dyskinesia

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
DNAH1	HGNC:2940	ENSG00000114841	Q9P2D7	Dynein axonemal heavy chain 1	gencc,clinvar
AFG2A	HGNC:18119	ENSG00000145375	Q8NB90	ATPase family gene 2 protein homolog A	clinvar
DNAH11	HGNC:2942	ENSG00000105877	Q96DT5	Dynein axonemal heavy chain 11	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNAH1	Dynein axonemal heavy chain 1	Force generating protein of cilia required for sperm flagellum motility.
AFG2A	ATPase family gene 2 protein homolog A	ATP-dependent chaperone part of the 55LCC heterohexameric ATPase complex which is chromatin-associated and promotes replisome proteostasis to maintain replication fork progression and genome stability.
DNAH11	Dynein axonemal heavy chain 11	Force generating protein required for cilia beating in respiratory epithelia.

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)
DNAH1	Other/Unknown	no		Dhc_D6_P-loop, Dhc_linker, Dhc_D4
AFG2A	Other/Unknown	no		AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS
DNAH11	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail

Expression context

Cohort genes with no expression data: 0.

3 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
bronchial epithelial cell	2
bronchus	2
right uterine tube	2
calcaneal tendon	1
tendon	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNAH1	183	tissue_specific	marker	right uterine tube, bronchial epithelial cell, bronchus
AFG2A	211	ubiquitous	marker	tendon of biceps brachii, calcaneal tendon, tendon
DNAH11	163	broad	marker	right uterine tube, bronchial epithelial cell, bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AFG2A	3,394
DNAH1	1,699
DNAH11	1,666

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DNAH1	Q9P2D7	2
AFG2A	Q8NB90	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DNAH11	Q96DT5

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 3 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 left/right asymmetry in nervous system	1	2808.7×	0.003	DNAH11
flagellated sperm motility	2	78.0×	0.003	DNAH1, DNAH11
protein localization to motile cilium	1	1123.5×	0.005	DNAH11
regulation of cilium beat frequency	1	702.2×	0.006	DNAH11
cilium-dependent cell motility	1	468.1×	0.006	DNAH1
epithelial cilium movement involved in determination of left/right asymmetry	1	432.1×	0.006	DNAH11
cardiac septum morphogenesis	1	401.2×	0.006	DNAH11
inner dynein arm assembly	1	295.6×	0.007	DNAH1
epithelial cilium movement involved in extracellular fluid movement	1	255.3×	0.007	DNAH1
cilium movement involved in cell motility	1	224.7×	0.008	DNAH11
sperm axoneme assembly	1	156.0×	0.010	DNAH1
ribosomal large subunit biogenesis	1	147.8×	0.010	AFG2A
determination of left/right symmetry	1	85.1×	0.015	DNAH11
learning or memory	1	80.2×	0.015	DNAH11
brain development	1	26.5×	0.042	AFG2A
spermatogenesis	1	11.7×	0.088	AFG2A
cell differentiation	1	9.7×	0.100	AFG2A

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DNAH1	0	0
AFG2A	0	0
DNAH11	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
AFG2A	2	Binding:2

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	0
E	Difficult family or no structure, no drug	3	DNAH1, AFG2A, DNAH11

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)
DNAH1	0	—
AFG2A	2	—
DNAH11	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.