Primary ciliary dyskinesia 12

Summary

Primary ciliary dyskinesia 12 (MONDO:0012979) is a disease caused by RSPH9 (GenCC Strong), with 4 cohort genes.

At a glance

• Causal gene: RSPH9 (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 37

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 12
Mondo ID	MONDO:0012979
MeSH	C567211
OMIM	612650
DOID	DOID:0110601
UMLS	C2675228
MedGen	436379
GARD	0015575
Is cancer (heuristic)	no

Also known as: CILD12 · ciliary dyskinesia, primary, 12 · ciliary dyskinesia, primary, type 12 · primary ciliary dyskinesia caused by mutation in RSPH9 · primary ciliary dyskinesia type 12 · RSPH9 primary ciliary dyskinesia

Data availability: 37 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 12

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 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

37 retrieved; paginated sample, class counts are floors:

20 uncertain significance, 7 conflicting classifications of pathogenicity, 3 benign, 3 pathogenic, 2 benign/likely benign, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4755432	Single allele	COL10A1	Pathogenic	criteria provided, single submitter
3393107	NM_152732.5(RSPH9):c.800_*71del (p.Glu267fs)	RSPH9	Pathogenic	criteria provided, single submitter
66994	NM_152732.5(RSPH9):c.801GAA[1] (p.Lys268del)	RSPH9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
66995	NM_152732.5(RSPH9):c.52C>T (p.Gln18Ter)	RSPH9	Pathogenic	no assertion criteria provided
3382264	NM_152732.5(RSPH9):c.19del (p.Leu7fs)	RSPH9	Likely pathogenic	criteria provided, single submitter
165063	NM_152732.5(RSPH9):c.421G>A (p.Val141Met)	RSPH9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1767533	NM_152732.5(RSPH9):c.95T>C (p.Leu32Pro)	RSPH9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
216823	NM_152732.5(RSPH9):c.798C>T (p.Gly266=)	RSPH9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357018	NM_152732.5(RSPH9):c.512G>A (p.Arg171Gln)	RSPH9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357020	NM_152732.5(RSPH9):c.819C>T (p.Pro273=)	RSPH9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
912058	NM_152732.5(RSPH9):c.393+13G>A	RSPH9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1038336	NM_152703.5(SAMD9L):c.1549T>C (p.Trp517Arg)	SAMD9L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4157448	NM_001010892.3(RSPH4A):c.1955A>G (p.Tyr652Cys)	RSPH4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1376100	NM_152732.5(RSPH9):c.272A>G (p.Glu91Gly)	RSPH9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1444848	NM_152732.5(RSPH9):c.281C>T (p.Ala94Val)	RSPH9	Uncertain significance	criteria provided, multiple submitters, no conflicts
220293	NM_152732.5(RSPH9):c.415C>T (p.Arg139Cys)	RSPH9	Uncertain significance	criteria provided, multiple submitters, no conflicts
2435487	NM_152732.5(RSPH9):c.825G>C (p.Met275Ile)	RSPH9	Uncertain significance	criteria provided, multiple submitters, no conflicts
2608222	NM_152732.5(RSPH9):c.605T>G (p.Leu202Arg)	RSPH9	Uncertain significance	criteria provided, multiple submitters, no conflicts
357016	NM_152732.5(RSPH9):c.276G>A (p.Met92Ile)	RSPH9	Uncertain significance	criteria provided, multiple submitters, no conflicts
357017	NM_152732.5(RSPH9):c.385G>A (p.Glu129Lys)	RSPH9	Uncertain significance	criteria provided, multiple submitters, no conflicts
357019	NM_152732.5(RSPH9):c.598A>G (p.Thr200Ala)	RSPH9	Uncertain significance	criteria provided, single submitter
3654723	NM_152732.5(RSPH9):c.157_174del (p.Leu53_Tyr58del)	RSPH9	Uncertain significance	criteria provided, multiple submitters, no conflicts
3764784	NM_152732.5(RSPH9):c.228-10T>G	RSPH9	Uncertain significance	criteria provided, single submitter
454994	NM_152732.5(RSPH9):c.760C>T (p.Arg254Cys)	RSPH9	Uncertain significance	criteria provided, multiple submitters, no conflicts
908041	NM_152732.5(RSPH9):c.648C>A (p.Ser216=)	RSPH9	Uncertain significance	criteria provided, single submitter
908042	NM_152732.5(RSPH9):c.787G>A (p.Val263Met)	RSPH9	Uncertain significance	criteria provided, multiple submitters, no conflicts
908043	NM_152732.5(RSPH9):c.804G>C (p.Lys268Asn)	RSPH9	Uncertain significance	criteria provided, single submitter
908044	NM_152732.5(RSPH9):c.806A>T (p.Asn269Ile)	RSPH9	Uncertain significance	criteria provided, single submitter
909997	NM_152732.5(RSPH9):c.*13C>A	RSPH9	Uncertain significance	criteria provided, single submitter
910837	NM_152732.5(RSPH9):c.112G>T (p.Asp38Tyr)	RSPH9	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 6 · 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
RSPH9	Strong	Autosomal recessive	primary ciliary dyskinesia 12	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RSPH9	Orphanet:244	Primary ciliary dyskinesia
SAMD9L	Orphanet:2585	Ataxia-pancytopenia syndrome
SAMD9L	Orphanet:619367	SAMD9L-associated autoinflammatory syndrome
SAMD9L	Orphanet:631106	Spinocerebellar ataxia type 49
RSPH4A	Orphanet:244	Primary ciliary dyskinesia
COL10A1	Orphanet:174	Metaphyseal chondrodysplasia, Schmid type

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RSPH9	HGNC:21057	ENSG00000172426	Q9H1X1	Radial spoke head protein 9 homolog	gencc,clinvar
SAMD9L	HGNC:1349	ENSG00000177409	Q8IVG5	Sterile alpha motif domain-containing protein 9-like	clinvar
RSPH4A	HGNC:21558	ENSG00000111834	Q5TD94	Radial spoke head protein 4 homolog A	clinvar
COL10A1	HGNC:2185	ENSG00000123500	Q03692	Collagen alpha-1(X) chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RSPH9	Radial spoke head protein 9 homolog	Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.
SAMD9L	Sterile alpha motif domain-containing protein 9-like	May be involved in endosome fusion.
RSPH4A	Radial spoke head protein 4 homolog A	Component of the axonemal radial spoke head which plays an important role in ciliary motility.
COL10A1	Collagen alpha-1(X) chain	Type X collagen is a product of hypertrophic chondrocytes and has been localized to presumptive mineralization zones of hyaline cartilage.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 4 · 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	4	1.8×	0.097

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RSPH9	Other/Unknown	no		RSP9
SAMD9L	Other/Unknown	no		SAM, SAM/pointed_sf
RSPH4A	Other/Unknown	no		Radial_spoke
COL10A1	Other/Unknown	no		C1q_dom, Collagen, Tumour_necrosis_fac-like_dom

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
mucosa of paranasal sinus	2
buccal mucosa cell	2
bronchial epithelial cell	1
bronchus	1
leukocyte	1
pancreatic ductal cell	1
olfactory segment of nasal mucosa	1
right uterine tube	1
periodontal ligament	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RSPH9	167	broad	marker	bronchial epithelial cell, bronchus, mucosa of paranasal sinus
SAMD9L	231	ubiquitous	marker	pancreatic ductal cell, buccal mucosa cell, leukocyte
RSPH4A	164	tissue_specific	marker	right uterine tube, olfactory segment of nasal mucosa, mucosa of paranasal sinus
COL10A1	162	broad	marker	tibia, periodontal ligament, buccal mucosa cell

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL10A1	1,949
RSPH4A	1,637
SAMD9L	1,608
RSPH9	1,230

Intra-cohort edges

A	B	Sources
RSPH4A	RSPH9	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RSPH9	Q9H1X1	1
RSPH4A	Q5TD94	1
COL10A1	Q03692	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SAMD9L	Q8IVG5	83.85

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 4 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Collagen chain trimerization	1	259.6×	0.007	COL10A1
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.007	COL10A1
Collagen degradation	1	175.7×	0.007	COL10A1
Collagen biosynthesis and modifying enzymes	1	170.4×	0.007	COL10A1
Non-integrin membrane-ECM interactions	1	154.3×	0.007	COL10A1
Integrin cell surface interactions	1	134.3×	0.007	COL10A1

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
radial spoke assembly	2	3744.9×	6e-07	RSPH9, RSPH4A
cilium movement involved in cell motility	2	449.4×	3e-05	RSPH9, RSPH4A
axoneme assembly	2	362.4×	3e-05	RSPH9, RSPH4A
cilium movement	2	261.3×	5e-05	RSPH9, RSPH4A
maintenance of ciliary planar beating movement pattern	1	5617.3×	4e-04	RSPH4A
axonemal central apparatus assembly	1	936.2×	0.002	RSPH9
epithelial cilium movement involved in extracellular fluid movement	1	255.3×	0.006	RSPH4A
motile cilium assembly	1	193.7×	0.006	RSPH9
establishment of localization in cell	1	53.5×	0.021	RSPH4A
skeletal system development	1	41.9×	0.024	COL10A1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 4 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
RSPH9	0	0
SAMD9L	0	0
RSPH4A	0	0
COL10A1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	4	RSPH9, SAMD9L, RSPH4A, COL10A1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RSPH9	0	—
SAMD9L	0	—
RSPH4A	0	—
COL10A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.