Ciliary dyskinesia, primary, 39

Summary

Ciliary dyskinesia, primary, 39 (MONDO:0032637) is a disease caused by LRRC56 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: LRRC56 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 26

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ciliary dyskinesia, primary, 39
Mondo ID	MONDO:0032637
OMIM	618254
DOID	DOID:0111854
UMLS	C4748841
MedGen	1648363
GARD	0025710
Is cancer (heuristic)	no

Also known as: CILD39

Data availability: 26 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 › ciliary dyskinesia, primary, 39

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 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, 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

26 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
2050626	NM_198075.4(LRRC56):c.159C>A (p.Tyr53Ter)	LRRC56	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
599210	NM_198075.4(LRRC56):c.423+1G>A	LRRC56	Pathogenic	no assertion criteria provided
599211	NM_198075.4(LRRC56):c.419T>C (p.Leu140Pro)	LRRC56	Pathogenic	no assertion criteria provided
599212	NM_198075.4(LRRC56):c.760G>T (p.Glu254Ter)	LRRC56	Pathogenic	criteria provided, single submitter
599213	NM_198075.4(LRRC56):c.326+1G>A	LRRC56	Pathogenic	no assertion criteria provided
4372415	NM_198075.4(LRRC56):c.1316-2A>G	LRRC56	Likely pathogenic	criteria provided, single submitter
4845867	NM_198075.4(LRRC56):c.1398_1404dup (p.Ser469fs)	LRRC56	Likely pathogenic	criteria provided, single submitter
1662645	NM_198075.4(LRRC56):c.1291T>A (p.Ser431Thr)	LRRC56	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3064490	NM_198075.4(LRRC56):c.494T>C (p.Leu165Pro)	LRRC56	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1370786	NM_198075.4(LRRC56):c.972T>C (p.His324=)	LRRC56	Uncertain significance	criteria provided, multiple submitters, no conflicts
1386531	NM_198075.4(LRRC56):c.914C>A (p.Pro305His)	LRRC56	Uncertain significance	criteria provided, multiple submitters, no conflicts
1523693	NM_198075.4(LRRC56):c.53_55del (p.Val18_Arg19delinsGly)	LRRC56	Uncertain significance	criteria provided, multiple submitters, no conflicts
3599790	NM_198075.4(LRRC56):c.424-14C>G	LRRC56	Uncertain significance	criteria provided, single submitter
1233089	NM_198075.4(LRRC56):c.899G>A (p.Arg300His)	LRRC56	Benign	criteria provided, multiple submitters, no conflicts
1245409	NM_198075.4(LRRC56):c.1182-22T>C	LRRC56	Benign	criteria provided, multiple submitters, no conflicts
1249013	NM_198075.4(LRRC56):c.1400G>A (p.Arg467Gln)	LRRC56	Benign	criteria provided, multiple submitters, no conflicts
1252876	NM_198075.4(LRRC56):c.384C>T (p.Leu128=)	LRRC56	Benign	criteria provided, multiple submitters, no conflicts
1257303	NM_198075.4(LRRC56):c.*23C>G	LRRC56	Benign	criteria provided, multiple submitters, no conflicts
1261003	NM_198075.4(LRRC56):c.729G>A (p.Pro243=)	LRRC56	Benign	criteria provided, multiple submitters, no conflicts
1268835	NM_198075.4(LRRC56):c.423+30C>G	LRRC56	Benign	criteria provided, multiple submitters, no conflicts
1278878	NM_198075.4(LRRC56):c.1567G>C (p.Asp523His)	LRRC56	Benign	criteria provided, multiple submitters, no conflicts
1286573	NM_198075.4(LRRC56):c.1519C>G (p.Arg507Gly)	LRRC56	Benign	criteria provided, multiple submitters, no conflicts
1535836	NM_198075.4(LRRC56):c.424-9G>A	LRRC56	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1569956	NM_198075.4(LRRC56):c.655G>A (p.Val219Met)	LRRC56	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1598826	NM_198075.4(LRRC56):c.35G>A (p.Arg12Gln)	LRRC56	Benign	criteria provided, multiple submitters, no conflicts
1601027	NM_198075.4(LRRC56):c.544C>A (p.Gln182Lys)	LRRC56	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

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
LRRC56	Strong	Autosomal recessive	ciliary dyskinesia, primary, 39	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LRRC56	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
LRRC56	HGNC:25430	ENSG00000161328	Q8IYG6	Leucine-rich repeat-containing protein 56	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LRRC56	Leucine-rich repeat-containing protein 56	Required for the assembly of dynein arms.

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)
LRRC56	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_4, LRR_dom_sf

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
left testis	1
right testis	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LRRC56	129	broad	marker	right uterine tube, right testis, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LRRC56	914

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LRRC56	Q8IYG6	56.07

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
cell projection organization	1	374.5×	0.003	LRRC56

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
LRRC56	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	LRRC56

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)
LRRC56	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.