Primary ciliary dyskinesia 16

Summary

Primary ciliary dyskinesia 16 (MONDO:0013525) is a disease caused by DNAL1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: DNAL1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 103

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 16
Mondo ID	MONDO:0013525
OMIM	614017
DOID	DOID:0110613
UMLS	C3151460
MedGen	462810
GARD	0015743
Is cancer (heuristic)	no

Also known as: CILD16 · ciliary dyskinesia, primary, 16 · ciliary dyskinesia, primary, type 16 · DNAL1 primary ciliary dyskinesia · primary ciliary dyskinesia caused by mutation in DNAL1 · primary ciliary dyskinesia type 16

Data availability: 103 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 16

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 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

103 retrieved; paginated sample, class counts are floors:

59 likely benign, 25 uncertain significance, 7 pathogenic, 4 benign, 4 conflicting classifications of pathogenicity, 3 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3244015	NC_000014.8:g.(?74111743)(74551097_?)del	ALDH6A1	Pathogenic	criteria provided, single submitter
228252	NM_031427.4(DNAL1):c.224_230del (p.Ile74_Leu75insTer)	DNAL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2426971	NC_000014.8:g.(?74153942)(74156238_?)del	DNAL1	Pathogenic	criteria provided, single submitter
2955850	NM_031427.4(DNAL1):c.296G>A (p.Trp99Ter)	DNAL1	Pathogenic	criteria provided, single submitter
30816	NM_031427.4(DNAL1):c.449A>G (p.Asn150Ser)	DNAL1	Pathogenic	criteria provided, single submitter
406527	NM_031427.4(DNAL1):c.486G>A (p.Trp162Ter)	DNAL1	Pathogenic	criteria provided, single submitter
406536	NM_031427.4(DNAL1):c.384del (p.Asp129fs)	DNAL1	Pathogenic	criteria provided, single submitter
662859	NC_000014.9:g.(?73671522)(73671617_?)del	DNAL1	Pathogenic	criteria provided, single submitter
3576682	NM_031427.4(DNAL1):c.151G>T (p.Glu51Ter)	DNAL1	Likely pathogenic	criteria provided, single submitter
3576683	NM_031427.4(DNAL1):c.438_439dup (p.Phe147fs)	DNAL1	Likely pathogenic	criteria provided, single submitter
3576684	NM_031427.4(DNAL1):c.490G>T (p.Glu164Ter)	DNAL1	Likely pathogenic	criteria provided, single submitter
178765	NM_031427.4(DNAL1):c.415C>G (p.Leu139Val)	DNAL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
195386	NM_031427.4(DNAL1):c.4-15T>C	DNAL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
261960	NM_031427.4(DNAL1):c.43-4A>G	DNAL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
497477	NM_031427.4(DNAL1):c.517C>T (p.Leu173=)	DNAL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
656294	NC_000014.8:g.(?74111723)(74727642_?)dup	ALDH6A1	Uncertain significance	criteria provided, single submitter
1004436	NM_031427.4(DNAL1):c.530A>G (p.Asp177Gly)	DNAL1	Uncertain significance	criteria provided, single submitter
1378690	NM_031427.4(DNAL1):c.136A>G (p.Met46Val)	DNAL1	Uncertain significance	criteria provided, single submitter
1687458	NM_031427.4(DNAL1):c.263T>C (p.Leu88Pro)	DNAL1	Uncertain significance	criteria provided, single submitter
2004901	NM_031427.4(DNAL1):c.16A>G (p.Thr6Ala)	DNAL1	Uncertain significance	criteria provided, single submitter
2021509	NM_031427.4(DNAL1):c.516del (p.Lys172fs)	DNAL1	Uncertain significance	criteria provided, single submitter
2098165	NM_031427.4(DNAL1):c.559G>A (p.Glu187Lys)	DNAL1	Uncertain significance	criteria provided, single submitter
2176179	NM_031427.4(DNAL1):c.200A>G (p.Asn67Ser)	DNAL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
220484	NM_031427.4(DNAL1):c.81G>C (p.Glu27Asp)	DNAL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2317773	NM_031427.4(DNAL1):c.469T>G (p.Ser157Ala)	DNAL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
314018	NM_031427.4(DNAL1):c.490G>A (p.Glu164Lys)	DNAL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
417385	NC_000014.9:g.(?73671542)(73671597_?)del	DNAL1	Uncertain significance	criteria provided, single submitter
4617729	NM_031427.4(DNAL1):c.442G>A (p.Val148Ile)	DNAL1	Uncertain significance	criteria provided, multiple submitters, no conflicts
471908	NM_031427.4(DNAL1):c.533-2A>G	DNAL1	Uncertain significance	criteria provided, single submitter
4723169	NM_031427.4(DNAL1):c.505_508dup (p.Val170fs)	DNAL1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
DNAL1	Strong	Autosomal recessive	primary ciliary dyskinesia 16	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNAL1	Orphanet:244	Primary ciliary dyskinesia
ALDH6A1	Orphanet:289307	Developmental delay due to methylmalonate semialdehyde dehydrogenase deficiency

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
DNAL1	HGNC:23247	ENSG00000119661	Q4LDG9	Dynein axonemal light chain 1	gencc,clinvar
ALDH6A1	HGNC:7179	ENSG00000119711	Q02252	Methylmalonate-semialdehyde/malonate-semialdehyde dehydrogenase [acylating], mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNAL1	Dynein axonemal light chain 1	Part of the multisubunit axonemal ATPase complexes that generate the force for cilia motility and govern beat frequency.
ALDH6A1	Methylmalonate-semialdehyde/malonate-semialdehyde dehydrogenase [acylating], mitochondrial	Malonate and methylmalonate semialdehyde dehydrogenase involved in the catabolism of valine, thymine, and compounds catabolized by way of beta-alanine, including uracil and cytidine.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNAL1	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_4, LRR_dom_sf
ALDH6A1	Enzyme (other)	yes	1.2.1.18	MeMal-semiAld_DH, Aldehyde_DH_dom, Ald_DH_CS_CYS

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
buccal mucosa cell	1
left testis	1
oviduct epithelium	1
adult organism	1
nephron tubule	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNAL1	224	ubiquitous	marker	buccal mucosa cell, oviduct epithelium, left testis
ALDH6A1	293	ubiquitous	marker	adult organism, nephron tubule, renal medulla

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALDH6A1	1,906
DNAL1	1,371

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ALDH6A1	Q02252	5
DNAL1	Q4LDG9	1

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
Branched-chain amino acid catabolism	1	475.8×	0.006	ALDH6A1
Metabolism of amino acids and derivatives	1	67.6×	0.022	ALDH6A1
Metabolism	1	11.6×	0.086	ALDH6A1

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
obsolete valine metabolic process	1	8426.0×	4e-04	ALDH6A1
thymine metabolic process	1	8426.0×	4e-04	ALDH6A1
thymine catabolic process	1	2808.7×	8e-04	ALDH6A1
L-valine catabolic process	1	1685.2×	0.001	ALDH6A1
branched-chain amino acid catabolic process	1	526.6×	0.003	ALDH6A1
outer dynein arm assembly	1	366.4×	0.003	DNAL1
brown fat cell differentiation	1	216.1×	0.005	ALDH6A1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
DNAL1	0	0
ALDH6A1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALDH6A1	1.2.1.18, 1.2.1.27	malonate-semialdehyde dehydrogenase (acetylating), methylmalonate-semialdehyde dehydrogenase (CoA-acylating)

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	1	ALDH6A1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	DNAL1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DNAL1	0	—
ALDH6A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.