Primary ciliary dyskinesia 32

Summary

Primary ciliary dyskinesia 32 (MONDO:0014657) is a disease caused by RSPH3 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: RSPH3 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 278

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 32
Mondo ID	MONDO:0014657
OMIM	616481
DOID	DOID:0110603
UMLS	C4225311
MedGen	896106
GARD	0016122
Is cancer (heuristic)	no

Also known as: CILD32 · ciliary dyskinesia, primary, 32 · ciliary dyskinesia, primary, type 32 · primary ciliary dyskinesia caused by mutation in RSPH3 · primary ciliary dyskinesia type 32 · RSPH3 primary ciliary dyskinesia

Data availability: 278 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 32

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 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

278 retrieved; paginated sample, class counts are floors:

115 uncertain significance, 104 likely benign, 24 pathogenic, 17 benign, 6 benign/likely benign, 6 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1031472	NM_031924.8(RSPH3):c.-143del	RSPH3	Pathogenic	criteria provided, single submitter
1301790	NM_031924.8(RSPH3):c.-260dup	RSPH3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1366054	NM_031924.8(RSPH3):c.-95G>A	RSPH3	Pathogenic	criteria provided, multiple submitters, no conflicts
1375407	NC_000006.11:g.(?159420447)(159421008_?)del	RSPH3	Pathogenic	criteria provided, single submitter
1420769	NM_031924.8(RSPH3):c.-417A>T	RSPH3	Pathogenic	criteria provided, single submitter
1455833	NM_031924.8(RSPH3):c.-220del	RSPH3	Pathogenic	criteria provided, single submitter
1456876	NC_000006.11:g.(?159414851)(159414978_?)del	RSPH3	Pathogenic	criteria provided, single submitter
1457344	NM_031924.8(RSPH3):c.-302_-301del	RSPH3	Pathogenic	criteria provided, single submitter
1514354	NM_031924.8(RSPH3):c.859+1G>A	RSPH3	Pathogenic	criteria provided, single submitter
1937576	NM_031924.8(RSPH3):c.-292del	RSPH3	Pathogenic	criteria provided, single submitter
204498	NM_031924.8(RSPH3):c.190C>T (p.Gln64Ter)	RSPH3	Pathogenic	no assertion criteria provided
204500	NM_031924.8(RSPH3):c.766C>T (p.Arg256Ter)	RSPH3	Pathogenic	no assertion criteria provided
204501	NM_031924.8(RSPH3):c.894_897del (p.Asn298fs)	RSPH3	Pathogenic	no assertion criteria provided
204502	NM_031924.8(RSPH3):c.679C>T (p.Arg227Ter)	RSPH3	Pathogenic	no assertion criteria provided
209010	NM_031924.8(RSPH3):c.205-2A>G	RSPH3	Pathogenic	criteria provided, multiple submitters, no conflicts
2804278	NM_031924.8(RSPH3):c.-88_-86del	RSPH3	Pathogenic	criteria provided, single submitter
2843362	NM_031924.8(RSPH3):c.-5del	RSPH3	Pathogenic	criteria provided, single submitter
2895815	NM_031924.8(RSPH3):c.-273G>T	RSPH3	Pathogenic	criteria provided, single submitter
2980542	NM_031924.8(RSPH3):c.859+1G>T	RSPH3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3253653	NM_031924.8(RSPH3):c.454dup (p.Thr152fs)	RSPH3	Pathogenic	criteria provided, single submitter
3651133	NM_031924.8(RSPH3):c.330del (p.His110fs)	RSPH3	Pathogenic	criteria provided, single submitter
3705611	NM_031924.8(RSPH3):c.-261_-260del	RSPH3	Pathogenic	criteria provided, single submitter
570047	NM_031924.8(RSPH3):c.685C>T (p.Arg229Ter)	RSPH3	Pathogenic	criteria provided, single submitter
646115	NM_031924.8(RSPH3):c.-207TG[1]	RSPH3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
650363	NM_031924.8(RSPH3):c.169C>T (p.Arg57Ter)	RSPH3	Pathogenic	criteria provided, single submitter
665656	NC_000006.12:g.(?158980754)(158986441_?)del	RSPH3	Pathogenic	criteria provided, single submitter
946339	NM_031924.8(RSPH3):c.823_824del (p.Arg275fs)	RSPH3	Pathogenic	criteria provided, single submitter
1526208	NM_031924.8(RSPH3):c.346+1G>T	RSPH3	Likely pathogenic	criteria provided, single submitter
2671830	NM_031924.8(RSPH3):c.280C>T (p.Gln94Ter)	RSPH3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4748136	NM_031924.8(RSPH3):c.346+1del	RSPH3	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
RSPH3	Definitive	Autosomal recessive	primary ciliary dyskinesia 32	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RSPH3	Orphanet:244	Primary ciliary dyskinesia

Cohort genes → proteins

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RSPH3	HGNC:21054	ENSG00000130363	Q86UC2	Radial spoke head protein 3 homolog	gencc,clinvar
FNDC1	HGNC:21184	ENSG00000164694	Q4ZHG4	Fibronectin type III domain-containing protein 1	clinvar
TAGAP-AS1	HGNC:55239	ENSG00000271913		TAGAP antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RSPH3	Radial spoke head protein 3 homolog	Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.
FNDC1	Fibronectin type III domain-containing protein 1	May be an activator of G protein signaling.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Antibody/Immunoglobulin	1	9.7×	0.199
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RSPH3	Other/Unknown	no		Radial_spoke_3
FNDC1	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, FN3_sf
TAGAP-AS1	Other/Unknown	no

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
bronchus	1
oviduct epithelium	1
cartilage tissue	1
synovial joint	1
tendon of biceps brachii	1
bone marrow	1
bone marrow cell	1
granulocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RSPH3	243	ubiquitous	marker	bronchial epithelial cell, oviduct epithelium, bronchus
FNDC1	183	broad	marker	tendon of biceps brachii, synovial joint, cartilage tissue
TAGAP-AS1	134	ubiquitous	yes	bone marrow cell, bone marrow, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RSPH3	2,848
FNDC1	897
TAGAP-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RSPH3	Q86UC2	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FNDC1	Q4ZHG4	54.19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 3 evidence-associated genes (0 with Reactome annotation).

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
RSPH3	0	0
FNDC1	0	0
TAGAP-AS1	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	1	FNDC1
E	Difficult family or no structure, no drug	2	RSPH3, TAGAP-AS1

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)
RSPH3	0	—
FNDC1	0	—
TAGAP-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.