Ciliary dyskinesia, primary, 50

Summary

Ciliary dyskinesia, primary, 50 (MONDO:0957252) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 24

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ciliary dyskinesia, primary, 50
Mondo ID	MONDO:0957252
OMIM	620356
UMLS	C5830473
MedGen	1841109
GARD	0026797
Is cancer (heuristic)	no

Data availability: 24 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, 50

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, 37, ciliary dyskinesia, primary, 38, ciliary dyskinesia, primary, 54, ciliary dyskinesia, primary, 49, without situs inversus, 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

24 retrieved; paginated sample, class counts are floors:

8 no classifications from unflagged records, 8 likely pathogenic, 4 uncertain significance, 3 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4278008	NM_018897.3(DNAH7):c.4647+1G>A	DNAH7	Pathogenic	criteria provided, single submitter
4056355	NM_018897.3(DNAH7):c.3135dup (p.Ser1046fs)	DNAH7	Likely pathogenic	criteria provided, single submitter
4277793	NM_018897.3(DNAH7):c.7045_7049delinsC (p.Ser2349fs)	DNAH7	Likely pathogenic	criteria provided, single submitter
4279591	NM_018897.3(DNAH7):c.11869-2A>C	DNAH7	Likely pathogenic	criteria provided, single submitter
4279638	NM_018897.3(DNAH7):c.870-1G>T	DNAH7	Likely pathogenic	criteria provided, single submitter
4845224	NM_018897.3(DNAH7):c.6404dup (p.Leu2135fs)	DNAH7	Likely pathogenic	criteria provided, single submitter
4845666	NM_018897.3(DNAH7):c.4309C>T (p.Arg1437Ter)	DNAH7	Likely pathogenic	criteria provided, single submitter
4845708	NM_018897.3(DNAH7):c.5276G>A (p.Trp1759Ter)	DNAH7	Likely pathogenic	criteria provided, single submitter
4845917	NM_018897.3(DNAH7):c.10799G>A (p.Trp3600Ter)	DNAH7	Likely pathogenic	criteria provided, single submitter
2500170	NM_018897.3(DNAH7):c.6492G>A (p.Met2164Ile)	DNAH7	Conflicting classifications of pathogenicity	no assertion criteria provided
3336813	NM_018897.3(DNAH7):c.3025C>T (p.Arg1009Ter)	DNAH7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2959185	NM_001372.4(DNAH9):c.12406C>T (p.Arg4136Ter)	DNAH9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2500168	NM_018897.3(DNAH7):c.10390G>A (p.Gly3464Ser)	DNAH7	no classifications from unflagged records	no classifications from unflagged records
2500169	NM_018897.3(DNAH7):c.5587G>A (p.Asp1863Asn)	DNAH7	no classifications from unflagged records	no classifications from unflagged records
2500171	NM_018897.3(DNAH7):c.9611G>A (p.Arg3204His)	DNAH7	no classifications from unflagged records	no classifications from unflagged records
2500172	NM_018897.3(DNAH7):c.10601A>G (p.Gln3534Arg)	DNAH7	no classifications from unflagged records	no classifications from unflagged records
2500173	NM_018897.3(DNAH7):c.2478dup (p.Val827fs)	DNAH7	no classifications from unflagged records	no classifications from unflagged records
3064757	NM_018897.3(DNAH7):c.9888+1G>A	DNAH7	no classifications from unflagged records	no classifications from unflagged records
3065247	NM_018897.3(DNAH7):c.6311C>G (p.Pro2104Arg)	DNAH7	Uncertain significance	criteria provided, single submitter
3065248	NM_018897.3(DNAH7):c.6347A>G (p.Asn2116Ser)	DNAH7	Uncertain significance	criteria provided, multiple submitters, no conflicts
3065318	NM_018897.3(DNAH7):c.1754+1G>A	DNAH7	no classifications from unflagged records	no classifications from unflagged records
3065342	NM_018897.3(DNAH7):c.5411del (p.Leu1804fs)	DNAH7	no classifications from unflagged records	no classifications from unflagged records
3067995	NM_018897.3(DNAH7):c.10971C>A (p.Ser3657Arg)	DNAH7	Uncertain significance	criteria provided, single submitter
4277844	NM_018897.3(DNAH7):c.7042_7043insCC (p.Gln2348fs)	DNAH7	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
DNAH7	Strong	Autosomal recessive	primary ciliary dyskinesia	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNAH7	Orphanet:244	Primary ciliary dyskinesia
DNAH9	Orphanet:101063	Situs inversus totalis
DNAH9	Orphanet:157769	Situs ambiguus
DNAH9	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
DNAH7	HGNC:18661	ENSG00000118997	Q8WXX0	Dynein axonemal heavy chain 7	gencc,clinvar
DNAH9	HGNC:2953	ENSG00000007174	Q9NYC9	Dynein axonemal heavy chain 9	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNAH7	Dynein axonemal heavy chain 7	Force generating protein that plays an important role in respiratory cilia and sperm flagella beating.
DNAH9	Dynein axonemal heavy chain 9	Force generating protein required for cilia beating in respiratory epithelia.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNAH7	Other/Unknown	no		EF_hand_dom, AAA+_ATPase, Dhc_D6_P-loop
DNAH9	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail

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	2
epithelium of bronchus	2
right uterine tube	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNAH7	212	broad	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus
DNAH9	184	broad	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DNAH9	1,841
DNAH7	1,537

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DNAH7	Q8WXX0	2
DNAH9	Q9NYC9	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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 2 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	2	674.1×	2e-05	DNAH7, DNAH9
cilium movement	2	391.9×	3e-05	DNAH7, DNAH9
cilium-dependent cell motility	1	702.2×	0.003	DNAH7
mucociliary clearance	1	648.1×	0.003	DNAH9
inner dynein arm assembly	1	443.5×	0.003	DNAH7
cerebrospinal fluid circulation	1	443.5×	0.003	DNAH9
cell projection organization	1	187.2×	0.006	DNAH9
establishment of localization in cell	1	80.2×	0.012	DNAH9

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
DNAH7	0	0
DNAH9	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	DNAH7, DNAH9

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)
DNAH7	0	—
DNAH9	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.