Primary ciliary dyskinesia 22

Summary

Primary ciliary dyskinesia 22 (MONDO:0014192) is a disease caused by ZMYND10 (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: ZMYND10 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 34

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 22
Mondo ID	MONDO:0014192
OMIM	615444
DOID	DOID:0110597
UMLS	C3809543
MedGen	815873
GARD	0015968
Is cancer (heuristic)	no

Also known as: CILD22 · ciliary dyskinesia, primary, 22 · ciliary dyskinesia, primary, type 22 · primary ciliary dyskinesia caused by mutation in ZMYND10 · primary ciliary dyskinesia type 22 · ZMYND10 primary ciliary dyskinesia

Data availability: 34 ClinVar variants · 4 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 22

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 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

34 retrieved; paginated sample, class counts are floors:

10 pathogenic, 5 uncertain significance, 5 benign/likely benign, 5 likely pathogenic, 3 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic, 2 likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1460085	NM_001277115.2(DNAH11):c.860dup (p.Asn287fs)	DNAH11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1332867	NM_015896.4(ZMYND10):c.747del (p.Ser250fs)	ZMYND10	Pathogenic	criteria provided, single submitter
1705506	NM_015896.4(ZMYND10):c.490C>T (p.Gln164Ter)	ZMYND10	Pathogenic	criteria provided, multiple submitters, no conflicts
2040520	NM_015896.4(ZMYND10):c.183_187del (p.Leu62fs)	ZMYND10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3383004	NM_015896.4(ZMYND10):c.31del (p.Glu11fs)	ZMYND10	Pathogenic	criteria provided, single submitter
3617264	NM_015896.4(ZMYND10):c.931C>T (p.Gln311Ter)	ZMYND10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3775188	NM_015896.4(ZMYND10):c.700+2T>C	ZMYND10	Pathogenic	criteria provided, single submitter
66021	NM_015896.4(ZMYND10):c.47T>G (p.Val16Gly)	ZMYND10	Pathogenic	criteria provided, multiple submitters, no conflicts
66022	NM_015896.4(ZMYND10):c.300del (p.Phe101fs)	ZMYND10	Pathogenic	criteria provided, single submitter
66023	NM_015896.4(ZMYND10):c.486dup (p.Ser163fs)	ZMYND10	Pathogenic	no assertion criteria provided
66024	NM_015896.4(ZMYND10):c.967C>T (p.Gln323Ter)	ZMYND10	Pathogenic	criteria provided, single submitter
66025	NM_015896.4(ZMYND10):c.593_594del (p.Val198fs)	ZMYND10	Pathogenic	no assertion criteria provided
66026	NM_015896.4(ZMYND10):c.797T>C (p.Leu266Pro)	ZMYND10	Pathogenic	criteria provided, multiple submitters, no conflicts
4820192	NM_001277115.2(DNAH11):c.6475C>T (p.Gln2159Ter)	DNAH11	Likely pathogenic	criteria provided, single submitter
3370459	NM_015896.4(ZMYND10):c.1024G>T (p.Glu342Ter)	RASSF1	Likely pathogenic	criteria provided, single submitter
2431468	NM_015896.4(ZMYND10):c.510+1del	ZMYND10	Likely pathogenic	criteria provided, single submitter
2626965	NM_015896.4(ZMYND10):c.1248-1G>T	ZMYND10	Likely pathogenic	criteria provided, single submitter
3255381	NM_015896.4(ZMYND10):c.967del (p.Gln323fs)	ZMYND10	Likely pathogenic	criteria provided, single submitter
1438577	NM_015896.4(ZMYND10):c.778G>A (p.Gly260Arg)	ZMYND10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
410633	NM_015896.4(ZMYND10):c.229G>A (p.Ala77Thr)	ZMYND10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
639060	NM_015896.4(ZMYND10):c.485G>A (p.Gly162Glu)	ZMYND10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1806284	NM_015896.4(ZMYND10):c.373-1G>A	ZMYND10	Uncertain significance	criteria provided, single submitter
454842	NM_015896.4(ZMYND10):c.637C>T (p.His213Tyr)	ZMYND10	Uncertain significance	criteria provided, multiple submitters, no conflicts
574473	NM_015896.4(ZMYND10):c.1171C>T (p.Arg391Trp)	ZMYND10	Uncertain significance	criteria provided, multiple submitters, no conflicts
646011	NM_015896.4(ZMYND10):c.235G>A (p.Glu79Lys)	ZMYND10	Uncertain significance	criteria provided, multiple submitters, no conflicts
961694	NM_015896.4(ZMYND10):c.1291G>A (p.Val431Ile)	ZMYND10	Uncertain significance	criteria provided, multiple submitters, no conflicts
1656861	NM_015896.4(ZMYND10):c.88G>A (p.Glu30Lys)	ZMYND10	Likely benign	criteria provided, multiple submitters, no conflicts
241065	NM_015896.4(ZMYND10):c.1019G>A (p.Arg340Gln)	ZMYND10	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
241066	NM_015896.4(ZMYND10):c.1073A>G (p.Gln358Arg)	ZMYND10	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
241067	NM_015896.4(ZMYND10):c.1105C>T (p.Arg369Trp)	ZMYND10	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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
ZMYND10	Strong	Autosomal recessive	primary ciliary dyskinesia 22	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ZMYND10	Orphanet:244	Primary ciliary dyskinesia
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
ZMYND10	HGNC:19412	ENSG00000004838	O75800	Zinc finger MYND domain-containing protein 10	gencc,clinvar
DNAH11	HGNC:2942	ENSG00000105877	Q96DT5	Dynein axonemal heavy chain 11	clinvar
RASSF1	HGNC:9882	ENSG00000068028	Q9NS23	Ras association domain-containing protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZMYND10	Zinc finger MYND domain-containing protein 10	Plays a role in axonemal structure organization and motility.
DNAH11	Dynein axonemal heavy chain 11	Force generating protein required for cilia beating in respiratory epithelia.
RASSF1	Ras association domain-containing protein 1	Potential tumor suppressor.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	2.8×	0.587
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ZMYND10	Transcription factor	no		Znf_MYND, UCP037948_Znf-MYND, ZMYND10
DNAH11	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
RASSF1	Other/Unknown	no		RA_dom, PKC_DAG/PE, SARAH_dom

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
right uterine tube	2
left testis	1
right testis	1
bronchial epithelial cell	1
bronchus	1
granulocyte	1
tibial nerve	1
upper lobe of left lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZMYND10	175	broad	marker	right uterine tube, left testis, right testis
DNAH11	163	broad	marker	right uterine tube, bronchial epithelial cell, bronchus
RASSF1	203	ubiquitous	marker	granulocyte, tibial nerve, upper lobe of left lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RASSF1	2,238
DNAH11	1,666
ZMYND10	1,317

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ZMYND10	O75800	2
RASSF1	Q9NS23	1

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
positive regulation of motile cilium assembly	1	5617.3×	0.004	ZMYND10
determination of left/right asymmetry in nervous system	1	2808.7×	0.004	DNAH11
protein localization to motile cilium	1	1123.5×	0.006	DNAH11
regulation of cilium beat frequency	1	702.2×	0.007	DNAH11
regulation of cell cycle G1/S phase transition	1	510.7×	0.007	RASSF1
epithelial cilium movement involved in determination of left/right asymmetry	1	432.1×	0.007	DNAH11
cardiac septum morphogenesis	1	401.2×	0.007	DNAH11
inner dynein arm assembly	1	295.6×	0.009	ZMYND10
outer dynein arm assembly	1	244.2×	0.009	ZMYND10
cilium movement involved in cell motility	1	224.7×	0.009	DNAH11
motile cilium assembly	1	193.7×	0.010	ZMYND10
protein localization to cilium	1	133.8×	0.012	ZMYND10
cilium movement	1	130.6×	0.012	ZMYND10
determination of left/right symmetry	1	85.1×	0.017	DNAH11
learning or memory	1	80.2×	0.017	DNAH11
positive regulation of protein ubiquitination	1	71.1×	0.018	RASSF1
Ras protein signal transduction	1	68.5×	0.018	RASSF1
flagellated sperm motility	1	39.0×	0.030	DNAH11
regulation of cell cycle	1	24.9×	0.044	RASSF1
protein stabilization	1	22.3×	0.046	RASSF1
DNA damage response	1	17.8×	0.055	RASSF1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 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
ZMYND10	0	0
DNAH11	0	0
RASSF1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	ZMYND10, DNAH11, RASSF1

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)
ZMYND10	0	—
DNAH11	0	—
RASSF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.