Primary ciliary dyskinesia 6

Summary

Primary ciliary dyskinesia 6 (MONDO:0012571) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 357

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 6
Mondo ID	MONDO:0012571
MeSH	C567057
OMIM	610852
DOID	DOID:0110606
UMLS	C1970506
MedGen	370930
GARD	0015502
Is cancer (heuristic)	no

Also known as: CILD6 · ciliary dyskinesia, primary, 6 · ciliary dyskinesia, primary, type 6 · NME8 primary ciliary dyskinesia · primary ciliary dyskinesia caused by mutation in NME8 · primary ciliary dyskinesia type 6

Data availability: 357 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 6

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 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

357 retrieved; paginated sample, class counts are floors:

209 uncertain significance, 112 likely benign, 19 benign, 9 benign/likely benign, 8 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1738397	NM_016616.5(NME8):c.416A>T (p.Asp139Val)	NME8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1789278	NM_016616.5(NME8):c.1090G>T (p.Glu364Ter)	NME8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2001991	NM_016616.5(NME8):c.1417G>A (p.Val473Ile)	NME8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241113	NM_016616.5(NME8):c.610A>G (p.Ile204Val)	NME8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
379360	NM_016616.5(NME8):c.271-11T>A	NME8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
409674	NM_016616.5(NME8):c.401C>T (p.Pro134Leu)	NME8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
565917	NM_016616.5(NME8):c.311C>T (p.Pro104Leu)	NME8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
570688	NM_016616.5(NME8):c.742C>A (p.Pro248Thr)	NME8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1412049	NC_000007.13:g.(?36429636)(37956139_?)dup	MATCAP2	Uncertain significance	criteria provided, single submitter
1013923	NM_016616.5(NME8):c.1545G>A (p.Val515=)	NME8	Uncertain significance	criteria provided, single submitter
1017316	NM_016616.5(NME8):c.1600C>G (p.Arg534Gly)	NME8	Uncertain significance	criteria provided, single submitter
1019571	NM_016616.5(NME8):c.365C>G (p.Ala122Gly)	NME8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1027035	NM_016616.5(NME8):c.23T>A (p.Val8Asp)	NME8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1036346	NM_016616.5(NME8):c.1624G>C (p.Glu542Gln)	NME8	Uncertain significance	criteria provided, single submitter
1037079	NM_016616.5(NME8):c.706C>T (p.Pro236Ser)	NME8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1052344	NM_016616.5(NME8):c.953C>G (p.Thr318Arg)	NME8	Uncertain significance	criteria provided, single submitter
1053075	NM_016616.5(NME8):c.171C>G (p.Asn57Lys)	NME8	Uncertain significance	criteria provided, single submitter
1053136	NM_016616.5(NME8):c.1459T>A (p.Phe487Ile)	NME8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1061153	NM_016616.5(NME8):c.679G>A (p.Val227Ile)	NME8	Uncertain significance	criteria provided, single submitter
1354867	NM_016616.5(NME8):c.845A>G (p.His282Arg)	NME8	Uncertain significance	criteria provided, single submitter
1362369	NM_016616.5(NME8):c.382C>T (p.Pro128Ser)	NME8	Uncertain significance	criteria provided, single submitter
1365823	NM_016616.5(NME8):c.569C>G (p.Thr190Arg)	NME8	Uncertain significance	criteria provided, single submitter
1390295	NM_016616.5(NME8):c.1097A>G (p.Glu366Gly)	NME8	Uncertain significance	criteria provided, single submitter
1393708	NM_016616.5(NME8):c.485C>T (p.Pro162Leu)	NME8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1403932	NM_016616.5(NME8):c.165A>T (p.Glu55Asp)	NME8	Uncertain significance	criteria provided, single submitter
1422969	NM_016616.5(NME8):c.921T>A (p.Phe307Leu)	NME8	Uncertain significance	criteria provided, single submitter
1444642	NC_000007.13:g.(?37889849)(37936714_?)del	NME8	Uncertain significance	criteria provided, single submitter
1445830	NM_016616.5(NME8):c.172G>A (p.Glu58Lys)	NME8	Uncertain significance	criteria provided, multiple submitters, no conflicts
1472682	NM_016616.5(NME8):c.461T>A (p.Leu154Ter)	NME8	Uncertain significance	criteria provided, single submitter
1485585	NM_016616.5(NME8):c.1092A>T (p.Glu364Asp)	NME8	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
NME8	Supportive	Autosomal dominant	primary ciliary dyskinesia	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NME8	Orphanet:244	Primary ciliary dyskinesia

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
NME8	HGNC:16473	ENSG00000086288	Q8N427	Protein NME8	gencc,clinvar
MATCAP2	HGNC:22206	ENSG00000164542	Q8NCT3	Putative tyrosine carboxypeptidase MATCAP2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NME8	Protein NME8	Possesses an intrinsic kinase activity.
MATCAP2	Putative tyrosine carboxypeptidase MATCAP2	Putative tyrosine carboxypeptidase.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NME8	Other/Unknown	no		Thioredoxin_domain, Thioredoxin_CS, NDK-like_dom
MATCAP2	Other/Unknown	no		MATCAP

Expression context

Cohort genes with no expression data: 0.

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
primordial germ cell in gonad	2
granulocyte	1
male germ line stem cell (sensu Vertebrata) in testis	1
bronchial epithelial cell	1
choroid plexus epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NME8	155		yes	granulocyte, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
MATCAP2	249	ubiquitous	yes	choroid plexus epithelium, bronchial epithelial cell, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NME8	8,310
MATCAP2	229

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NME8	Q8N427	79.81
MATCAP2	Q8NCT3	59.68

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
DNA catabolic process	1	468.1×	0.015	NME8
cellular response to reactive oxygen species	1	205.5×	0.017	NME8
flagellated sperm motility	1	58.5×	0.040	NME8
cilium assembly	1	36.8×	0.047	NME8
spermatogenesis	1	17.6×	0.067	NME8
proteolysis	1	17.1×	0.067	MATCAP2
cell differentiation	1	14.6×	0.068	NME8

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
NME8	0	0
MATCAP2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	NME8, MATCAP2

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)
NME8	0	—
MATCAP2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.