Primary ciliary dyskinesia 11

Summary

Primary ciliary dyskinesia 11 (MONDO:0012978) is a disease caused by RSPH4A (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: RSPH4A (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 88

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 11
Mondo ID	MONDO:0012978
MeSH	C567212
OMIM	612649
DOID	DOID:0110602
UMLS	C2675229
MedGen	390741
GARD	0015574
Is cancer (heuristic)	no

Also known as: CILD11 · ciliary dyskinesia, primary, 11 · ciliary dyskinesia, primary, type 11 · primary ciliary dyskinesia 11 · primary ciliary dyskinesia caused by mutation in RSPH4A · primary ciliary dyskinesia type 11 · RSPH4A primary ciliary dyskinesia

Data availability: 88 ClinVar variants · 3 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 11

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 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

88 retrieved; paginated sample, class counts are floors:

37 uncertain significance, 16 conflicting classifications of pathogenicity, 14 pathogenic, 7 benign/likely benign, 7 benign, 3 pathogenic/likely pathogenic, 2 likely pathogenic, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
666983	NM_001010892.3(RSPH4A):c.116C>A (p.Ser39Ter)	LOC129997052	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069488	NM_001010892.3(RSPH4A):c.1558C>T (p.Arg520Ter)	RSPH4A	Pathogenic	criteria provided, multiple submitters, no conflicts
1330295	NM_001010892.3(RSPH4A):c.1631G>A (p.Trp544Ter)	RSPH4A	Pathogenic	criteria provided, single submitter
3600353	NM_001010892.3(RSPH4A):c.160C>T (p.Gln54Ter)	RSPH4A	Pathogenic	criteria provided, single submitter
441117	NM_001010892.3(RSPH4A):c.1662+2_1662+5del	RSPH4A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4537496	NM_001010892.3(RSPH4A):c.1963_1966del (p.Asp655fs)	RSPH4A	Pathogenic	criteria provided, single submitter
454520	NM_001010892.3(RSPH4A):c.1351C>T (p.Gln451Ter)	RSPH4A	Pathogenic	criteria provided, multiple submitters, no conflicts
454521	NM_001010892.3(RSPH4A):c.1453C>T (p.Arg485Ter)	RSPH4A	Pathogenic	criteria provided, multiple submitters, no conflicts
4819014	NM_001010892.3(RSPH4A):c.844G>T (p.Glu282Ter)	RSPH4A	Pathogenic	criteria provided, single submitter
503	NM_001010892.3(RSPH4A):c.460C>T (p.Gln154Ter)	RSPH4A	Pathogenic	criteria provided, multiple submitters, no conflicts
504	NM_001010892.3(RSPH4A):c.325C>T (p.Gln109Ter)	RSPH4A	Pathogenic	criteria provided, single submitter
505	NM_001010892.3(RSPH4A):c.1468C>T (p.Arg490Ter)	RSPH4A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
525269	NM_001010892.3(RSPH4A):c.430C>T (p.Gln144Ter)	RSPH4A	Pathogenic	criteria provided, multiple submitters, no conflicts
66992	NM_001010892.3(RSPH4A):c.667del (p.Ser223fs)	RSPH4A	Pathogenic	no assertion criteria provided
66993	NM_001010892.3(RSPH4A):c.1270del (p.Thr424fs)	RSPH4A	Pathogenic	criteria provided, single submitter
88863	NM_001010892.3(RSPH4A):c.921+3_921+6del	RSPH4A	Pathogenic	criteria provided, multiple submitters, no conflicts
957527	NM_001010892.3(RSPH4A):c.1774_1775del (p.Leu592fs)	RSPH4A	Pathogenic	criteria provided, multiple submitters, no conflicts
3382688	NM_001010892.3(RSPH4A):c.1213G>T (p.Glu405Ter)	RSPH4A	Likely pathogenic	criteria provided, single submitter
4818926	NM_001010892.3(RSPH4A):c.610_613dup (p.Ser205fs)	RSPH4A	Likely pathogenic	criteria provided, single submitter
165058	NM_001010892.3(RSPH4A):c.584C>G (p.Pro195Arg)	RSPH4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
197172	NM_001010892.3(RSPH4A):c.1708G>C (p.Glu570Gln)	RSPH4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
215480	NM_001010892.3(RSPH4A):c.1917-4A>G	RSPH4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
227901	NM_001010892.3(RSPH4A):c.1662+15C>T	RSPH4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
227903	NM_001010892.3(RSPH4A):c.1974A>G (p.Thr658=)	RSPH4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
257048	NM_001010892.3(RSPH4A):c.1563T>C (p.Asn521=)	RSPH4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355118	NM_001010892.3(RSPH4A):c.237A>G (p.Thr79=)	RSPH4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355119	NM_001010892.3(RSPH4A):c.930C>T (p.Asn310=)	RSPH4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355124	NM_001010892.3(RSPH4A):c.1990C>T (p.Pro664Ser)	RSPH4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355125	NM_001010892.3(RSPH4A):c.2101G>C (p.Glu701Gln)	RSPH4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
650407	NM_001010892.3(RSPH4A):c.1103T>G (p.Val368Gly)	RSPH4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
RSPH4A	Strong	Autosomal recessive	primary ciliary dyskinesia 11	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RSPH4A	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
RSPH4A	HGNC:21558	ENSG00000111834	Q5TD94	Radial spoke head protein 4 homolog A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RSPH4A	Radial spoke head protein 4 homolog A	Component of the axonemal radial spoke head which plays an important role in ciliary motility.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RSPH4A	Other/Unknown	no		Radial_spoke

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
mucosa of paranasal sinus	1
olfactory segment of nasal mucosa	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RSPH4A	164	tissue_specific	marker	right uterine tube, olfactory segment of nasal mucosa, mucosa of paranasal sinus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RSPH4A	1,637

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RSPH4A	Q5TD94	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
maintenance of ciliary planar beating movement pattern	1	16852.0×	4e-04	RSPH4A
radial spoke assembly	1	5617.3×	6e-04	RSPH4A
epithelial cilium movement involved in extracellular fluid movement	1	766.0×	0.003	RSPH4A
cilium movement involved in cell motility	1	674.1×	0.003	RSPH4A
axoneme assembly	1	543.6×	0.003	RSPH4A
cilium movement	1	391.9×	0.003	RSPH4A
establishment of localization in cell	1	160.5×	0.006	RSPH4A

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
RSPH4A	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	RSPH4A

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)
RSPH4A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.