Primary ciliary dyskinesia 5

Summary

Primary ciliary dyskinesia 5 (MONDO:0012088) is a disease caused by HYDIN (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: HYDIN (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 127

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 5
Mondo ID	MONDO:0012088
MeSH	C563886
OMIM	608647
DOID	DOID:0110617
UMLS	C1837615
MedGen	324840
GARD	0015438
Is cancer (heuristic)	no

Also known as: CILD5 · ciliary dyskinesia, primary, 5 · ciliary dyskinesia, primary, type 5 · HYDIN primary ciliary dyskinesia · primary ciliary dyskinesia caused by mutation in HYDIN · primary ciliary dyskinesia type 5

Data availability: 127 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 5

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 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, 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

127 retrieved; paginated sample, class counts are floors:

58 uncertain significance, 36 likely pathogenic, 16 pathogenic, 9 conflicting classifications of pathogenicity, 5 benign, 2 likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323082	NM_001270974.2(HYDIN):c.8008C>T (p.Gln2670Ter)	HYDIN	Pathogenic	criteria provided, single submitter
1323084	NM_001270974.2(HYDIN):c.3175C>T (p.Arg1059Ter)	HYDIN	Pathogenic	criteria provided, single submitter
3027473	NM_001270974.2(HYDIN):c.10012G>T (p.Glu3338Ter)	HYDIN	Pathogenic	criteria provided, single submitter
3027482	NM_001270974.2(HYDIN):c.1147C>T (p.Arg383Ter)	HYDIN	Pathogenic	criteria provided, single submitter
3027483	NM_001270974.2(HYDIN):c.4888A>T (p.Lys1630Ter)	HYDIN	Pathogenic	criteria provided, single submitter
3027487	NM_001270974.2(HYDIN):c.13709del (p.Pro4570fs)	HYDIN	Pathogenic	criteria provided, single submitter
3027488	NM_001270974.2(HYDIN):c.1529del (p.Phe510fs)	HYDIN	Pathogenic	criteria provided, single submitter
3027494	NM_001270974.2(HYDIN):c.3252dup (p.Val1085fs)	HYDIN	Pathogenic	criteria provided, single submitter
3893230	NM_001270974.2(HYDIN):c.2047G>T (p.Glu683Ter)	HYDIN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39699	NM_001270974.2(HYDIN):c.922A>T (p.Lys308Ter)	HYDIN	Pathogenic	no assertion criteria provided
4056784	NM_001270974.2(HYDIN):c.8674_8675delinsG (p.Gln2892fs)	HYDIN	Pathogenic	criteria provided, single submitter
4073579	NM_001270974.2(HYDIN):c.2616_2617insTGGCACTGAC (p.Leu873delinsTrpHisTer)	HYDIN	Pathogenic	criteria provided, single submitter
4755444	NM_001270974.2(HYDIN):c.1330C>T (p.Arg444Ter)	HYDIN	Pathogenic	criteria provided, single submitter
4819537	NM_001270974.2(HYDIN):c.6491C>A (p.Ser2164Ter)	HYDIN	Pathogenic	criteria provided, single submitter
65472	NM_001270974.2(HYDIN):c.3786-1G>T	HYDIN	Pathogenic	no assertion criteria provided
869381	NM_001270974.2(HYDIN):c.12530del (p.Pro4177fs)	HYDIN	Pathogenic	criteria provided, single submitter
39698	NM_001270974.2(HYDIN):c.3985G>T (p.Val1329Leu)	LOC121587554	Pathogenic	no assertion criteria provided
1324558	NM_001270974.2(HYDIN):c.9397C>T (p.Gln3133Ter)	HYDIN	Likely pathogenic	criteria provided, single submitter
1344890	NM_001270974.2(HYDIN):c.6344_6345dup (p.Ile2116fs)	HYDIN	Likely pathogenic	criteria provided, single submitter
1806491	NM_001270974.2(HYDIN):c.11712del (p.Gln3905fs)	HYDIN	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2431690	NM_001270974.2(HYDIN):c.3829_3832del (p.Leu1277fs)	HYDIN	Likely pathogenic	criteria provided, single submitter
2442393	NM_001270974.2(HYDIN):c.12444-1G>A	HYDIN	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2584824	NM_001270974.2(HYDIN):c.13402-2A>G	HYDIN	Likely pathogenic	criteria provided, single submitter
3027471	NM_001270974.2(HYDIN):c.15037_15048delinsGATGATATA (p.Tyr5013_Pro5016delinsAspAspIle)	HYDIN	Likely pathogenic	criteria provided, single submitter
3027472	NM_001270974.2(HYDIN):c.1670G>C (p.Arg557Thr)	HYDIN	Likely pathogenic	criteria provided, single submitter
3027474	NM_001270974.2(HYDIN):c.283C>T (p.Gln95Ter)	HYDIN	Likely pathogenic	criteria provided, single submitter
3027476	NM_001270974.2(HYDIN):c.2419_2422del (p.Val807fs)	HYDIN	Likely pathogenic	criteria provided, single submitter
3027477	NM_001270974.2(HYDIN):c.5620-311_5788+1198del	HYDIN	Likely pathogenic	criteria provided, single submitter
3027479	NM_001270974.2(HYDIN):c.1095del (p.Phe365fs)	HYDIN	Likely pathogenic	criteria provided, single submitter
3027480	NM_001270974.2(HYDIN):c.2376+752_2529+9004del	HYDIN	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 3 · 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
HYDIN	Definitive	Autosomal recessive	primary ciliary dyskinesia 5	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HYDIN	Orphanet:244	Primary ciliary dyskinesia
KCNN4	Orphanet:3202	Dehydrated hereditary stomatocytosis
KCNN4	Orphanet:586	Cystic fibrosis

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HYDIN	HGNC:19368	ENSG00000157423	Q4G0P3	Hydrocephalus-inducing protein homolog	gencc,clinvar
KCNN4	HGNC:6293	ENSG00000104783	O15554	Intermediate conductance calcium-activated potassium channel protein 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HYDIN	Hydrocephalus-inducing protein homolog	Required for ciliary motility.
KCNN4	Intermediate conductance calcium-activated potassium channel protein 4	Intermediate conductance calcium-activated potassium channel that mediates the voltage-independent transmembrane transfer of potassium across the cell membrane through a constitutive interaction with calmodulin which binds the intracellula…

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Ion channel	1	55.8×	0.036
Antibody/Immunoglobulin	1	14.6×	0.067

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HYDIN	Antibody/Immunoglobulin	yes		Ig-like_fold, P-loop_NTPase, Hydin-like
KCNN4	Ion channel	yes		CaM-bd_dom, K_chnl_dom, K_chnl_Ca-activ_SK

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus callosum	1
male germ line stem cell (sensu Vertebrata) in testis	1
right uterine tube	1
olfactory segment of nasal mucosa	1
parotid gland	1
saliva-secreting gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HYDIN	136	broad	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, corpus callosum
KCNN4	200	ubiquitous	marker	olfactory segment of nasal mucosa, parotid gland, saliva-secreting gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNN4	1,698
HYDIN	1,412

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCNN4	O15554	17
HYDIN	Q4G0P3	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 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
Ca2+ activated K+ channels	1	1142.0×	0.003	KCNN4
Potassium Channels	1	134.3×	0.011	KCNN4
Neuronal System	1	44.3×	0.023	KCNN4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
stabilization of membrane potential	1	2808.7×	0.004	KCNN4
trachea development	1	2808.7×	0.004	HYDIN
axonemal central apparatus assembly	1	1404.3×	0.004	HYDIN
regulation of calcium ion import across plasma membrane	1	1404.3×	0.004	KCNN4
saliva secretion	1	1053.2×	0.004	KCNN4
macropinocytosis	1	936.2×	0.004	KCNN4
epithelial cell development	1	766.0×	0.004	HYDIN
positive regulation of potassium ion transmembrane transport	1	495.6×	0.006	KCNN4
ventricular system development	1	421.3×	0.006	HYDIN
positive regulation of T cell receptor signaling pathway	1	383.0×	0.006	KCNN4
phospholipid translocation	1	312.1×	0.006	KCNN4
cell volume homeostasis	1	300.9×	0.006	KCNN4
immune system process	1	195.9×	0.008	KCNN4
cilium movement	1	195.9×	0.008	HYDIN
positive regulation of protein secretion	1	172.0×	0.009	KCNN4
protein homotetramerization	1	118.7×	0.012	KCNN4
defense response	1	108.0×	0.012	KCNN4
potassium ion transport	1	95.8×	0.013	KCNN4
calcium ion transport	1	90.6×	0.013	KCNN4
establishment of localization in cell	1	80.2×	0.014	KCNN4
potassium ion transmembrane transport	1	68.0×	0.015	KCNN4
actin cytoskeleton organization	1	39.6×	0.025	HYDIN

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
KCNN4	CLOTRIMAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KCNN4	2	4
HYDIN	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CLOTRIMAZOLE	4	KCNN4
SENICAPOC	3	KCNN4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
KCNN4	27	Binding:27

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

2 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.

Compound	Max phase	Cohort target (bioactivity)
CLOTRIMAZOLE	4	KCNN4
SENICAPOC	3	KCNN4

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	KCNN4
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	HYDIN
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
HYDIN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.