Primary ciliary dyskinesia 9

Summary

Primary ciliary dyskinesia 9 (MONDO:0012906) is a disease caused by DNAI2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: DNAI2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 135

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 9
Mondo ID	MONDO:0012906
MeSH	C567310
OMIM	612444
DOID	DOID:0110622
UMLS	C2676235
MedGen	390990
GARD	0015558
Is cancer (heuristic)	no

Also known as: CILD9 · ciliary dyskinesia, primary, 9 · ciliary dyskinesia, primary, type 9 · DNAI2 primary ciliary dyskinesia · primary ciliary dyskinesia 9 · primary ciliary dyskinesia caused by mutation in DNAI2 · primary ciliary dyskinesia type 9

Data availability: 135 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 9

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 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

135 retrieved; paginated sample, class counts are floors:

42 uncertain significance, 32 conflicting classifications of pathogenicity, 18 benign, 15 pathogenic/likely pathogenic, 11 likely pathogenic, 11 benign/likely benign, 4 pathogenic, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1071724	NM_023036.6(DNAI2):c.250del (p.Asp84fs)	DNAI2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075745	NM_023036.6(DNAI2):c.739C>T (p.Arg247Ter)	DNAI2	Pathogenic	criteria provided, multiple submitters, no conflicts
1312393	NM_023036.6(DNAI2):c.740G>A (p.Arg247Gln)	DNAI2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2119577	NM_023036.6(DNAI2):c.1173G>A (p.Trp391Ter)	DNAI2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
228335	NM_023036.6(DNAI2):c.1304G>A (p.Trp435Ter)	DNAI2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2632611	NM_023036.6(DNAI2):c.314_318del (p.Asn105fs)	DNAI2	Pathogenic/Likely pathogenic	no assertion criteria provided
2741230	NM_023036.6(DNAI2):c.231dup (p.Glu78fs)	DNAI2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2836226	NM_023036.6(DNAI2):c.1326C>A (p.Cys442Ter)	DNAI2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4081631	NM_023036.6(DNAI2):c.127G>T (p.Glu43Ter)	DNAI2	Pathogenic	criteria provided, single submitter
408961	NM_023036.6(DNAI2):c.883C>T (p.Arg295Ter)	DNAI2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
454933	NM_023036.6(DNAI2):c.1414C>T (p.Gln472Ter)	DNAI2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
454939	NM_023036.6(DNAI2):c.610+1G>A	DNAI2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4953	NM_023036.6(DNAI2):c.1494+1G>A	DNAI2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4954	NM_023036.6(DNAI2):c.346-3T>G	DNAI2	Pathogenic	criteria provided, multiple submitters, no conflicts
4955	NM_023036.6(DNAI2):c.787C>T (p.Arg263Ter)	DNAI2	Pathogenic	criteria provided, multiple submitters, no conflicts
525359	NM_023036.6(DNAI2):c.718C>T (p.Gln240Ter)	DNAI2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
567508	NM_023036.6(DNAI2):c.1422del (p.Thr475fs)	DNAI2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
851971	NM_023036.6(DNAI2):c.421G>T (p.Glu141Ter)	DNAI2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
860672	NM_023036.6(DNAI2):c.1429dup (p.Thr477fs)	DNAI2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1347762	NM_023036.6(DNAI2):c.1348-1G>A	DNAI2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1687254	NM_023036.6(DNAI2):c.341_344del (p.Gly114fs)	DNAI2	Likely pathogenic	criteria provided, single submitter
2439890	NM_023036.6(DNAI2):c.1631_1632insAGCG (p.Val545fs)	DNAI2	Likely pathogenic	criteria provided, single submitter
2501698	NM_023036.6(DNAI2):c.87dup (p.Asp30fs)	DNAI2	Likely pathogenic	criteria provided, single submitter
2577156	NM_023036.6(DNAI2):c.987+1G>A	DNAI2	Likely pathogenic	criteria provided, single submitter
3582812	NM_023036.6(DNAI2):c.219dup (p.Val74fs)	DNAI2	Likely pathogenic	criteria provided, single submitter
3582813	NM_023036.6(DNAI2):c.246_253delinsTCC (p.Lys83fs)	DNAI2	Likely pathogenic	criteria provided, single submitter
3582816	NM_023036.6(DNAI2):c.658del (p.Leu219_Val220insTer)	DNAI2	Likely pathogenic	criteria provided, single submitter
3582817	NM_023036.6(DNAI2):c.1215C>A (p.Tyr405Ter)	DNAI2	Likely pathogenic	criteria provided, single submitter
3582818	NM_023036.6(DNAI2):c.1723-1G>A	DNAI2	Likely pathogenic	criteria provided, single submitter
804422	NM_023036.6(DNAI2):c.674del (p.Asn225fs)	DNAI2	Likely pathogenic	criteria provided, single submitter

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
DNAI2	Strong	Autosomal recessive	primary ciliary dyskinesia 9	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNAI2	Orphanet:244	Primary ciliary dyskinesia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DNAI2	HGNC:18744	ENSG00000171595	Q9GZS0	Dynein axonemal intermediate chain 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNAI2	Dynein axonemal intermediate chain 2	Component of dynein, a family of motor proteins essential for movement along microtubules.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNAI2	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
epithelium of bronchus	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNAI2	115	tissue_specific	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
DNAI2	1,115

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DNAI2	Q9GZS0	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 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 1 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	1	732.7×	0.005	DNAI2
cilium movement	1	391.9×	0.005	DNAI2
determination of left/right symmetry	1	255.3×	0.005	DNAI2
cilium assembly	1	73.6×	0.014	DNAI2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
DNAI2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	DNAI2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DNAI2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.