Primary ciliary dyskinesia 21

Summary

Primary ciliary dyskinesia 21 (MONDO:0014123) is a disease caused by DRC1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: DRC1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 34

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 21
Mondo ID	MONDO:0014123
OMIM	615294
DOID	DOID:0110596
UMLS	C3809087
MedGen	815417
GARD	0015940
Is cancer (heuristic)	no

Also known as: CILD21 · ciliary dyskinesia, primary, 21 · ciliary dyskinesia, primary, type 21 · DRC1 primary ciliary dyskinesia · primary ciliary dyskinesia caused by mutation in DRC1 · primary ciliary dyskinesia type 21

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 21

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 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

34 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 6 benign, 4 pathogenic, 4 conflicting classifications of pathogenicity, 4 likely pathogenic, 3 pathogenic/likely pathogenic, 2 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1034291	NM_145038.5(DRC1):c.1976del (p.Ser659fs)	DRC1	Pathogenic	criteria provided, multiple submitters, no conflicts
1172761	NC_000002.12:g.26398040_26425787del	DRC1	Pathogenic	criteria provided, single submitter
2504575	NM_145038.5(DRC1):c.1009C>T (p.Gln337Ter)	DRC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4820312	NM_145038.5(DRC1):c.503del (p.Leu167_Leu168insTer)	DRC1	Pathogenic	criteria provided, single submitter
55839	NM_145038.5(DRC1):c.2056A>T (p.Lys686Ter)	DRC1	Pathogenic	no assertion criteria provided
55840	NM_145038.5(DRC1):c.352C>T (p.Gln118Ter)	DRC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
663966	NM_145038.5(DRC1):c.109dup (p.Gln37fs)	DRC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3367126	NM_145038.5(DRC1):c.1196G>A (p.Trp399Ter)	DRC1	Likely pathogenic	criteria provided, single submitter
4528941	NM_145038.5(DRC1):c.1945C>T (p.Gln649Ter)	DRC1	Likely pathogenic	criteria provided, single submitter
4528942	NM_145038.5(DRC1):c.1901del (p.Met634fs)	DRC1	Likely pathogenic	criteria provided, single submitter
525424	NM_145038.5(DRC1):c.1599+1G>A	DRC1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1374288	NM_145038.5(DRC1):c.1391G>A (p.Arg464His)	DRC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
454988	NM_145038.5(DRC1):c.2223A>C (p.Ter741Cys)	DRC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
525259	NM_145038.5(DRC1):c.2075C>G (p.Thr692Ser)	DRC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
695946	NM_145038.5(DRC1):c.1124G>A (p.Arg375His)	DRC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2428723	NM_145038.5(DRC1):c.116G>C (p.Arg39Pro)	DRC1	Uncertain significance	criteria provided, single submitter
3779288	NM_145038.5(DRC1):c.319C>G (p.His107Asp)	DRC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3779289	NM_145038.5(DRC1):c.349C>T (p.Arg117Cys)	DRC1	Uncertain significance	criteria provided, single submitter
407099	NM_145038.5(DRC1):c.421T>G (p.Trp141Gly)	DRC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
407102	NM_145038.5(DRC1):c.1418C>T (p.Ala473Val)	DRC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
454984	NM_145038.5(DRC1):c.1913A>C (p.Lys638Thr)	DRC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
525352	NM_145038.5(DRC1):c.2190_2193dup (p.Thr732fs)	DRC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
575005	NM_145038.5(DRC1):c.1424C>T (p.Ala475Val)	DRC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
657775	NM_145038.5(DRC1):c.1247C>G (p.Ala416Gly)	DRC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
948125	NM_145038.5(DRC1):c.2079_2086del (p.Arg694fs)	DRC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1627791	NM_145038.5(DRC1):c.2166+16_2166+17insA	DRC1	Benign	criteria provided, multiple submitters, no conflicts
2045269	NM_145038.5(DRC1):c.765+15C>T	DRC1	Likely benign	criteria provided, multiple submitters, no conflicts
241940	NM_145038.5(DRC1):c.36G>C (p.Pro12=)	DRC1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
262564	NM_145038.5(DRC1):c.1195T>C (p.Trp399Arg)	DRC1	Benign	criteria provided, multiple submitters, no conflicts
262565	NM_145038.5(DRC1):c.1397-15A>G	DRC1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
DRC1	Strong	Autosomal recessive	primary ciliary dyskinesia 21	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DRC1	Orphanet:244	Primary ciliary dyskinesia
DRC1	Orphanet:276234	Non-syndromic male infertility due to sperm motility disorder

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
DRC1	HGNC:24245	ENSG00000157856	Q96MC2	Dynein regulatory complex protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DRC1	Dynein regulatory complex protein 1	Component of the nexin-dynein regulatory complex (N-DRC) a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes.

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)
DRC1	Other/Unknown	no		DRC1_C, DRC1/2_N, DRC1/DRC2

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
bronchus	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DRC1	141	broad	marker	right uterine tube, bronchial epithelial cell, bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DRC1	465

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DRC1	Q96MC2	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
regulation of cilium movement	1	4213.0×	0.002	DRC1
cilium-dependent cell motility	1	1404.3×	0.002	DRC1
mucociliary clearance	1	1296.3×	0.002	DRC1
axonemal dynein complex assembly	1	1053.2×	0.002	DRC1
sperm flagellum assembly	1	674.1×	0.002	DRC1
determination of left/right symmetry	1	255.3×	0.005	DRC1
single fertilization	1	183.2×	0.006	DRC1
heart development	1	78.8×	0.013	DRC1

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
DRC1	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	DRC1

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)
DRC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.