CCDC39

Summary

CCDC39 (coiled-coil domain 39 molecular ruler complex subunit, HGNC:25244) is a protein-coding gene on chromosome 3q26.33, encoding Coiled-coil domain-containing protein 39 (Q9UFE4). Required for assembly of dynein regulatory complex (DRC) and inner dynein arm (IDA) complexes, which are responsible for ciliary beat regulation, thereby playing a central role in motility in cilia and flagella.

The protein encoded by this gene is involved in the motility of cilia and flagella. The encoded protein is essential for the assembly of dynein regulatory and inner dynein arm complexes, which regulate ciliary beat. Defects in this gene are a cause of primary ciliary dyskinesia type 14 (CILD14).

Source: NCBI Gene 339829 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary ciliary dyskinesia 14 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 951 total — 127 pathogenic, 37 likely-pathogenic
• Phenotypes (HPO): 66
• MANE Select transcript: NM_181426

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25244
Approved symbol	CCDC39
Name	coiled-coil domain 39 molecular ruler complex subunit
Location	3q26.33
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434A128, CILD14, FAP59, CFAP59
Ensembl gene	ENSG00000284862
Ensembl biotype	protein_coding
OMIM	613798
Entrez	339829

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 5 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000473854, ENST00000476379, ENST00000489868, ENST00000650641, ENST00000650889, ENST00000651046, ENST00000651818, ENST00000651922, ENST00000652010, ENST00000652024, ENST00000652408, ENST00000936067

RefSeq mRNA: 1 — MANE Select: NM_181426 NM_181426

CCDS: CCDS46964

Canonical transcript exons

ENST00000476379 — 20 exons

Exon	Start	End
ENSE00001727160	180619811	180619970
ENSE00003481747	180616281	180616363
ENSE00003590067	180616826	180616966
ENSE00003630286	180619259	180619365
ENSE00003688969	180616516	180616695
ENSE00003841654	180652163	180652266
ENSE00003841912	180651401	180651533
ENSE00003842695	180660570	180660728
ENSE00003842897	180647079	180647243
ENSE00003843014	180659677	180659769
ENSE00003843179	180659452	180659580
ENSE00003843392	180631469	180631592
ENSE00003846568	180679291	180679489
ENSE00003846667	180614008	180615077
ENSE00003847179	180654762	180654953
ENSE00003847574	180641993	180642201
ENSE00003847607	180661861	180662007
ENSE00003847813	180663867	180663986
ENSE00003849618	180648165	180648359
ENSE00003850735	180644120	180644257

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 95.19.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3205 / max 57.4145, expressed in 106 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45743	0.3205	106

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	95.19	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.19	gold quality
endometrium	UBERON:0001295	86.37	gold quality
right ovary	UBERON:0002118	86.18	gold quality
calcaneal tendon	UBERON:0003701	86.15	gold quality
pituitary gland	UBERON:0000007	86.03	gold quality
lymph node	UBERON:0000029	85.93	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.84	gold quality
adenohypophysis	UBERON:0002196	85.68	gold quality
left ovary	UBERON:0002119	85.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.20	gold quality
corpus callosum	UBERON:0002336	84.95	gold quality
cerebellar hemisphere	UBERON:0002245	84.59	gold quality
tibial nerve	UBERON:0001323	84.51	gold quality
left lobe of thyroid gland	UBERON:0001120	84.49	gold quality
cerebellar cortex	UBERON:0002129	84.44	gold quality
ovary	UBERON:0000992	84.34	gold quality
right lobe of thyroid gland	UBERON:0001119	84.32	gold quality
fallopian tube	UBERON:0003889	84.16	gold quality
thyroid gland	UBERON:0002046	84.11	gold quality
cerebellum	UBERON:0002037	84.06	gold quality
metanephros cortex	UBERON:0010533	84.02	gold quality
spleen	UBERON:0002106	83.62	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.47	gold quality
mucosa of stomach	UBERON:0001199	83.37	gold quality
body of pancreas	UBERON:0001150	83.20	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.11	gold quality
endocervix	UBERON:0000458	82.94	gold quality
ectocervix	UBERON:0012249	82.83	gold quality
right lung	UBERON:0002167	82.65	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-130148	yes	10.83
E-ANND-3	yes	6.39
E-MTAB-6379	no	4.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting CCDC39, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-4328	99.57	71.06	4094

Literature-anchored findings (GeneRIF, showing 9)

• Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex. (PMID:21131972)
• Aiming to delineate the CCDC39/CCDC40 mutation spectrum and associated phenotypes, a large cohort of patients with IDA defects were screened. Biallelic CCDC39 or CCDC40 mutations were identified in 30/34 unrelated families with IDA defects. (PMID:22693285)
• This study shows that CCDC39 and CCDC40 mutations are the major cause of Primary ciliary dyskinesia in patients with the previously termed “radial spoke defect”. (PMID:23255504)
• Lung disease was worse in those with IDA/CA/MTD ultrastructural defects, most of whom had biallelic mutations in ccdc39. (PMID:25493340)
• Clinical and genetic spectrum in 33 Egyptian families with suspected primary ciliary dyskinesia. (PMID:31650533)
• Deep phenotyping, including quantitative ciliary beating parameters, and extensive genotyping in primary ciliary dyskinesia. (PMID:31772028)
• A novel CCDC39 mutation causes multiple morphological abnormalities of the flagella in a primary ciliary dyskinesia patient. (PMID:34674941)
• Biallelic Variants in CCDC39 Gene Lead to Primary Ciliary Dyskinesia and Kartagener Syndrome. (PMID:35795318)
• Primary Ciliary Dyskinesia Associated Disease-Causing Variants in CCDC39 and CCDC40 Cause Axonemal Absence of Inner Dynein Arm Heavy Chains DNAH1, DNAH6, and DNAH7. (PMID:39056782)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	CCDC39	ENSDARG00000100981
mus_musculus	Ccdc39	ENSMUSG00000027676
rattus_norvegicus	Ccdc39	ENSRNOG00000011440
drosophila_melanogaster	Ccdc39	FBGN0037276

Protein

Protein identifiers

Coiled-coil domain-containing protein 39 — Q9UFE4 (reviewed: Q9UFE4)

All UniProt accessions (4): Q9UFE4, A0A494C1Q3, H7C4X6, H7C5I6

UniProt curated annotations — full annotation on UniProt →

Function. Required for assembly of dynein regulatory complex (DRC) and inner dynein arm (IDA) complexes, which are responsible for ciliary beat regulation, thereby playing a central role in motility in cilia and flagella. Probably acts together with CCDC40 to form a molecular ruler that determines the 96 nanometer (nm) repeat length and arrangements of components in cilia and flagella. Not required for outer dynein arm complexes assembly.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme.

Tissue specificity. Mainly expressed in nasal brushings and, to a lesser extent, in lungs and testis.

Disease relevance. Ciliary dyskinesia, primary, 14 (CILD14) [MIM:613807] A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. The disease is caused by variants affecting the gene represented in this entry. The disease is characterized by primary ciliary dyskinesia with inner dynein arm (IDA) defects and axonemal dizorganisation: defects in CCDC39 and CCDC40 constitute the major cause of this phenotype.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the CCDC39 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UFE4-1	1	yes
Q9UFE4-2	2

RefSeq proteins (1): NP_852091* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033290	CCDC39	Family

Pfam: PF24161

UniProt features (16 total): coiled-coil region 4, splice variant 3, sequence conflict 2, compositionally biased region 2, modified residue 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UFE4-F1	79.23	0.26

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 892, 900

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 247 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_NEURON_MATURATION, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_GLIAL_CELL_DEVELOPMENT, GOBP_NEUROGENESIS, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, chr3q26, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_PANCREAS_DEVELOPMENT, GOBP_SPECIFICATION_OF_SYMMETRY

GO Biological Process (31): heart looping (GO:0001947), cilium movement (GO:0003341), regulation of cilium beat frequency (GO:0003356), microglia differentiation (GO:0014004), cerebral cortex development (GO:0021987), central nervous system myelination (GO:0022010), flagellated sperm motility (GO:0030317), lung development (GO:0030324), determination of pancreatic left/right asymmetry (GO:0035469), inner dynein arm assembly (GO:0036159), locomotion (GO:0040011), neuron maturation (GO:0042551), motile cilium assembly (GO:0044458), cilium organization (GO:0044782), neuron projection morphogenesis (GO:0048812), establishment of localization in cell (GO:0051649), synapse maturation (GO:0060074), cilium-dependent cell motility (GO:0060285), epithelial cilium movement involved in determination of left/right asymmetry (GO:0060287), protein localization to cilium (GO:0061512), establishment of left/right asymmetry (GO:0061966), axonemal dynein complex assembly (GO:0070286), determination of digestive tract left/right asymmetry (GO:0071907), determination of liver left/right asymmetry (GO:0071910), cerebrospinal fluid circulation (GO:0090660), neuroinflammatory response (GO:0150076), epithelial cilium movement involved in extracellular fluid movement (GO:0003351), determination of left/right symmetry (GO:0007368), nervous system development (GO:0007399), brain development (GO:0007420), heart development (GO:0007507)

GO Molecular Function (0):

GO Cellular Component (8): extracellular region (GO:0005576), cytosol (GO:0005829), cilium (GO:0005929), axoneme (GO:0005930), motile cilium (GO:0031514), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
determination of left/right symmetry	2
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
microtubule-based movement	1
regulation of cilium movement	1
central nervous system development	1
glial cell differentiation	1
macrophage differentiation	1
pallium development	1
anatomical structure development	1
oligodendrocyte development	1
axon ensheathment in central nervous system	1
myelination	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
respiratory tube development	1
animal organ development	1
respiratory system development	1
pancreas development	1
axonemal dynein complex assembly	1
biological_process	1
cell maturation	1
neuron development	1
cilium assembly	1
organelle organization	1
plasma membrane bounded cell projection organization	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
establishment of localization	1
cellular localization	1
nervous system development	1
developmental maturation	1
synapse organization	1
cilium or flagellum-dependent cell motility	1
cilium movement	1
epithelial cilium movement involved in extracellular fluid movement	1
protein localization to organelle	1
cytoplasm	1

Protein interactions and networks

STRING

1194 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC39	CCDC40	Q4G0X9	995
CCDC39	DRC1	Q96MC2	867
CCDC39	DRC2	Q8IXS2	855
CCDC39	DNAAF3	Q8N9W5	829
CCDC39	RSPH9	Q9H1X1	828
CCDC39	RSPH4A	Q5TD94	820
CCDC39	DNAAF19	Q8IW40	819
CCDC39	DNAH5	Q8TE73	818
CCDC39	DNAI2	Q9GZS0	818
CCDC39	DNAAF11	Q86X45	804
CCDC39	DNAH11	Q96DT5	802
CCDC39	DNAI1	Q9UI46	802
CCDC39	DNAAF1	Q8NEP3	797
CCDC39	ODAD2	Q5T2S8	782
CCDC39	ZMYND10	O75800	775

IntAct

6 interactions, top by confidence:

A	B	Type	Score
DYNC1LI1	DYNC1LI2	psi-mi:“MI:0914”(association)	0.530
CCDC39	HYOU1	psi-mi:“MI:0915”(physical association)	0.400
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
YWHAH	BRAF	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): CCDC39 (Affinity Capture-MS), HYOU1 (Proximity Label-MS), CCDC39 (Affinity Capture-MS), CCDC39 (Affinity Capture-MS), CCDC39 (Affinity Capture-MS), TRO (Cross-Linking-MS (XL-MS)), PRCC (Cross-Linking-MS (XL-MS)), NEFM (Cross-Linking-MS (XL-MS)), TIPRL (Cross-Linking-MS (XL-MS)), CCDC39 (Cross-Linking-MS (XL-MS)), EEA1 (Cross-Linking-MS (XL-MS)), CD207 (Cross-Linking-MS (XL-MS)), TOPAZ1 (Cross-Linking-MS (XL-MS)), CCDC39 (Co-fractionation), CCDC39 (Affinity Capture-RNA)

ESM2 similar proteins: A8HUA1, A8I4E9, A8IQE0, A8JF70, B2GUE2, B2RW38, B6MFW3, D3Z8K2, E1BM70, E2R1I5, E9Q9F7, F1MA98, F1QNW4, F6ZDS4, M1V4Y8, O01789, O15697, O35594, P0CK98, P0DL09, P10999, P12270, P14732, P16568, P21910, P70403, P83829, Q03427, Q08C53, Q0V9R4, Q13948, Q2T9W6, Q567U6, Q5EE04, Q5R8V1, Q5T655, Q5TZ80, Q5ZKI4, Q640U7, Q66H60

Diamond homologs: A8IQE0, D3Z8K2, E1BM70, E2R1I5, Q0V9R4, Q9D5Y1, Q9UFE4, P0CK98

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

951 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	127
Likely pathogenic	37
Uncertain significance	269
Likely benign	384
Benign	53

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012311	NM_181426.2(CCDC39):c.2040_2043del (p.Cys680fs)	Pathogenic
1069445	NM_181426.2(CCDC39):c.1485dup (p.Ser496fs)	Pathogenic
1070035	NM_181426.2(CCDC39):c.1674_1675dup (p.Ile559fs)	Pathogenic
1073617	NM_181426.2(CCDC39):c.1208_1209insGGTGTGCTGTTGCGTGAACCTGGGAGGCGGAGCTTGCAGTGAGCCGAGATCGCGCCACTGCACTCCAGCCTGGGCGACAGAGCGAGACTCCGTCTCAAAAAAAAAAAAAAAAAGGTGTGCTGTT (p.Phe403fs)	Pathogenic
1322040	NM_181426.2(CCDC39):c.1456dup (p.Glu486fs)	Pathogenic
1344600	NM_181426.2(CCDC39):c.1356C>A (p.Tyr452Ter)	Pathogenic
1344601	NM_181426.2(CCDC39):c.436del (p.Trp146fs)	Pathogenic
1344602	NM_181426.2(CCDC39):c.1484_1485del (p.Lys495fs)	Pathogenic
1363237	NM_181426.2(CCDC39):c.2017G>T (p.Glu673Ter)	Pathogenic
1388230	NM_181426.2(CCDC39):c.2350C>T (p.Gln784Ter)	Pathogenic
1456279	NM_181426.2(CCDC39):c.2542_2546del (p.Glu848fs)	Pathogenic
1776672	NM_181426.2(CCDC39):c.1625_1632del (p.Arg542fs)	Pathogenic
1782193	NM_181426.2(CCDC39):c.1898_1901del (p.Ser633fs)	Pathogenic
1786892	NM_181426.2(CCDC39):c.216_217del (p.Cys73fs)	Pathogenic
1795913	NM_181426.2(CCDC39):c.277G>T (p.Glu93Ter)	Pathogenic
188300	NM_181426.2(CCDC39):c.526_527del (p.Leu176fs)	Pathogenic
1901749	NM_181426.2(CCDC39):c.841A>T (p.Lys281Ter)	Pathogenic
1916247	NM_181426.2(CCDC39):c.210+2T>C	Pathogenic
2027682	NC_000003.12:g.180652267_180652268insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGAGGTCAGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAGAATCCAGC	Pathogenic
2053107	NM_181426.2(CCDC39):c.891T>G (p.Tyr297Ter)	Pathogenic
2115243	NM_181426.2(CCDC39):c.2391_2394del (p.Glu797_Arg798insTer)	Pathogenic
216139	NM_181426.2(CCDC39):c.1644del (p.Asp548fs)	Pathogenic
216140	NM_181426.2(CCDC39):c.610-2A>G	Pathogenic
2166862	NM_181426.2(CCDC39):c.949dup (p.Thr317fs)	Pathogenic
2180412	NM_181426.2(CCDC39):c.610-2A>C	Pathogenic
2188873	NM_181426.2(CCDC39):c.2194C>T (p.Gln732Ter)	Pathogenic
2203463	NM_181426.2(CCDC39):c.485dup (p.Tyr163fs)	Pathogenic
242167	NM_181426.2(CCDC39):c.1073_1076del (p.Thr358fs)	Pathogenic
242169	NM_181426.2(CCDC39):c.163_164del (p.Met55fs)	Pathogenic
2694714	NM_181426.2(CCDC39):c.1381del (p.Val461fs)	Pathogenic

SpliceAI

4809 predictions. Top by Δscore:

Variant	Effect	Δscore
3:180602886:TTAAG:T	acceptor_loss	1.0000
3:180602887:TAAGA:T	acceptor_loss	1.0000
3:180602888:A:AG	acceptor_gain	1.0000
3:180602888:AAGAA:A	acceptor_loss	1.0000
3:180602889:A:G	acceptor_gain	1.0000
3:180602890:G:GC	acceptor_gain	1.0000
3:180602890:GA:G	acceptor_gain	1.0000
3:180602890:GAA:G	acceptor_gain	1.0000
3:180602890:GAAA:G	acceptor_gain	1.0000
3:180602890:GAAAA:G	acceptor_gain	1.0000
3:180603014:AGG:A	donor_loss	1.0000
3:180603016:G:GG	donor_gain	1.0000
3:180603016:GTC:G	donor_loss	1.0000
3:180603017:T:A	donor_loss	1.0000
3:180603021:T:G	donor_gain	1.0000
3:180603120:TTA:T	acceptor_loss	1.0000
3:180603122:A:AG	acceptor_gain	1.0000
3:180603122:AGAT:A	acceptor_loss	1.0000
3:180603123:G:GA	acceptor_gain	1.0000
3:180603123:GAT:G	acceptor_gain	1.0000
3:180603123:GATC:G	acceptor_gain	1.0000
3:180603123:GATCA:G	acceptor_gain	1.0000
3:180603229:G:GT	donor_gain	1.0000
3:180603283:G:GT	donor_gain	1.0000
3:180603319:TCACA:T	donor_gain	1.0000
3:180603320:CACA:C	donor_gain	1.0000
3:180603322:CA:C	donor_gain	1.0000
3:180603323:AGTAA:A	donor_loss	1.0000
3:180603324:G:C	donor_loss	1.0000
3:180603324:G:GG	donor_gain	1.0000

AlphaMissense

6307 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:180659511:A:G	W227R	0.994
3:180659511:A:T	W227R	0.994
3:180661950:C:G	A90P	0.994
3:180661995:C:G	A75P	0.994
3:180659562:C:G	A210P	0.993
3:180659522:A:G	L223P	0.992
3:180642071:C:G	R599P	0.991
3:180619275:A:G	L750P	0.990
3:180659565:C:G	A209P	0.990
3:180619948:A:G	L674P	0.989
3:180619967:C:G	A668P	0.988
3:180619970:C:G	A667P	0.987
3:180659682:C:G	A202P	0.986
3:180661931:C:G	R96P	0.985
3:180619907:C:G	A688P	0.983
3:180662003:A:G	L72P	0.983
3:180631554:A:G	L638P	0.982
3:180619873:A:G	L699P	0.981
3:180663925:C:G	R51P	0.981
3:180659549:C:G	R214P	0.979
3:180660650:A:G	W146R	0.979
3:180660650:A:T	W146R	0.979
3:180660653:C:G	A145P	0.978
3:180631544:T:A	R641S	0.977
3:180631544:T:G	R641S	0.977
3:180642170:A:G	L566P	0.977
3:180631575:C:G	R631P	0.976
3:180619885:A:G	L695P	0.975
3:180647218:C:G	R463P	0.975
3:180660662:C:G	A142P	0.975

dbSNP variants (sampled 300 via entrez): RS1000004216 (3:180617589 T>C), RS1000016331 (3:180663499 C>T), RS1000035459 (3:180617381 G>A), RS1000047663 (3:180620791 T>G), RS1000095153 (3:180613646 T>A), RS1000120597 (3:180619132 TATCTA>T), RS1000196138 (3:180650704 A>G), RS1000254233 (3:180639547 T>A,C), RS1000262079 (3:180644356 C>T), RS1000293436 (3:180631142 A>C), RS1000374371 (3:180680099 C>T), RS1000451241 (3:180663786 T>C), RS1000481091 (3:180658441 C>CA), RS1000508512 (3:180658196 G>A), RS1000591534 (3:180640761 A>C)

Disease associations

OMIM: gene MIM:613798 | disease phenotypes: MIM:244400, MIM:613807, MIM:225500

GenCC curated gene-disease

Disease	Classification	Inheritance
primary ciliary dyskinesia 14	Definitive	Autosomal recessive
primary ciliary dyskinesia	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
primary ciliary dyskinesia 14	Definitive	AR

Mondo (4): primary ciliary dyskinesia (MONDO:0016575), primary ciliary dyskinesia 14 (MONDO:0013434), infertility disorder (MONDO:0005047), Ellis-van Creveld syndrome (MONDO:0009162)

Orphanet (3): Primary ciliary dyskinesia (Orphanet:244), Ellis Van Creveld syndrome (Orphanet:289), Situs ambiguus (Orphanet:157769)

HPO phenotypes

66 total (30 of 66 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000119	Abnormality of the genitourinary system
HP:0000238	Hydrocephalus
HP:0000365	Hearing impairment
HP:0000388	Otitis media
HP:0000389	Chronic otitis media
HP:0000403	Recurrent otitis media
HP:0000405	Conductive hearing impairment
HP:0000510	Rod-cone dystrophy
HP:0000750	Delayed speech and language development
HP:0000924	Abnormality of the skeletal system
HP:0001217	Clubbing
HP:0001627	Abnormal heart morphology
HP:0001669	Transposition of the great arteries
HP:0001696	Situs inversus totalis
HP:0001719	Double outlet right ventricle
HP:0001742	Nasal congestion
HP:0001746	Asplenia
HP:0001748	Polysplenia
HP:0002011	Morphological central nervous system abnormality
HP:0002110	Bronchiectasis
HP:0002119	Ventriculomegaly
HP:0002205	Recurrent respiratory infections
HP:0002257	Chronic rhinitis
HP:0002566	Intestinal malrotation
HP:0002643	Neonatal respiratory distress
HP:0002878	Respiratory failure
HP:0003251	Male infertility
HP:0003577	Congenital onset
HP:0003593	Infantile onset

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002539_51	Schizophrenia	2.000000e-08
GCST004495_19	BMI (adjusted for smoking behaviour)	6.000000e-10
GCST004497_116	Body mass index (joint analysis main effects and smoking interaction)	1.000000e-10
GCST004498_5	BMI in smokers	8.000000e-07
GCST004499_20	BMI in non-smokers	3.000000e-06
GCST010989_235	Body size at age 10	5.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior
EFO:0004340	body mass index
EFO:0009819	comparative body size at age 10, self-reported

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D002925	Ciliary Motility Disorders	C08.200; C09.150; C16.131.077.245.500; C16.320.184.500
D004613	Ellis-Van Creveld Syndrome	C05.116.099.708.327; C16.131.077.350.398; C16.131.831.350.398; C16.320.850.250.398; C17.800.804.350.398; C17.800.827.250.398
D007246	Infertility	C12.100.750
D007619	Kartagener Syndrome	C08.127.384.500; C08.200.531; C08.695.501; C09.150.531; C14.240.400.280.500; C14.280.400.280.500; C16.131.077.245.500.531; C16.131.240.400.280.500; C16.131.740.501; C16.131.810.250.500; C16.320.184.500.531; C16.320.480

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	affects expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Air Pollutants	increases abundance, increases expression	1
Benzophenoneidum	increases expression	1
Phthalic Acids	decreases methylation	1
Smoke	increases abundance, increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

174 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01388907	PHASE4	COMPLETED	Efficacity Assessment of PREVADH® in Adhesion Prevention in Gynaecologic Surgery
NCT01430650	PHASE4	COMPLETED	Endometrial Priming for Embryo Transfer
NCT02607319	PHASE4	COMPLETED	Low Molecular Weight Heparin to Improve Pregnancy Outcome in Patients With Recurrent Implantation Failure
NCT03169166	PHASE4	COMPLETED	The Use of GnRH Agonist Trigger for Final Follicle Maturation in Women Undergoing Assisted Reproductive Technologies
NCT03177122	PHASE4	UNKNOWN	Myo-Inositol- Based Co-treatment in Women With PCOS Undergoing Assisted Reproductive Technology
NCT03477929	PHASE4	UNKNOWN	Cetrorelix and Ganirelix Flexible Protocol for (IVF)
NCT03619707	PHASE4	COMPLETED	Oral Versus Vaginal Progesterone in the Luteal Support in Cryo-warmed Embryo Transfer Cycles
NCT03846544	PHASE4	COMPLETED	Double Pick up in Poor Prognosis Women
NCT05725512	PHASE4	RECRUITING	Prednisolone Administration in Patients With Unexplained REcurrent MIscarriages
NCT06195163	PHASE4	NOT_YET_RECRUITING	TRAP Study: Testosterone for Androgen Receptor Polymorphism
NCT06763926	PHASE4	NOT_YET_RECRUITING	Intranasal Nafarelin For Triggering Oocyte Maturation
NCT00749853	PHASE3	SUSPENDED	Efficacy of Ovarian Stimulation Based on FSHR Genotype Status
NCT03238092	PHASE3	UNKNOWN	Comparison Between Testosterone and Estradiol Over the Homogenization of Follicular Cohort
NCT03803228	PHASE3	COMPLETED	Dual Ovarian Stimulation (DUOSTIM) for Poor Ovarian Responders
NCT02871778	PHASE2	COMPLETED	Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia
NCT07318974	PHASE2	ACTIVE_NOT_RECRUITING	Melatonin Therapy for Improving ICSI Outcomes in Women With Diminished Ovarian Reserve
NCT04701034	PHASE2	COMPLETED	Intravenous Immunoglobulin and Prednisolone for RPL After ART.
NCT04850261	PHASE2	WITHDRAWN	Injection Free IVF
NCT06997900	PHASE2	RECRUITING	Menopur And Rekovelle Combination Study Version 2.0
NCT05737485	PHASE1	COMPLETED	Study Evaluating the Safety and Tolerability of RCT1100 in Healthy and PCD Subjects
NCT06600425	PHASE1	COMPLETED	A Study to Assess the Safety, Tolerability, Ciliary Rescue, and Pharmacodynamics of RCT1100 in Adults With PCD
NCT06633757	PHASE1	COMPLETED	Study of Inhaled RCT1100 in Adults With PCD Caused by Pathogenic Mutations in the DNAI1 Gene to Measure Mucociliary Clearance
NCT04901715	EARLY_PHASE1	COMPLETED	Functional Studies of Novel Genes Mutated in Primary Ciliary Dyskinesia II: Genotype to Phenotype
NCT00005650	Not specified	COMPLETED	Genetic Study of Patients With Primary Ciliary Dyskinesia
NCT00323167	Not specified	COMPLETED	Rare Genetic Disorders of the Breathing Airways
NCT00368446	Not specified	COMPLETED	Genetic Disorders of Mucociliary Clearance in Nontuberculous Mycobacterial Lung Disease
NCT00450918	Not specified	COMPLETED	Evaluating Progression of and Diagnostic Tools for Primary Ciliary Dyskinesia in Children and Adolescents
NCT00608556	Not specified	COMPLETED	Dyskinesia, Heterotaxy and Congenital Heart Disease
NCT00686309	Not specified	UNKNOWN	Comparison of On-line and Off-line Measurements of Exhaled Nitric Oxide (NO)
NCT00722878	Not specified	COMPLETED	Long-term Lung Function and Disease Progression in Children With Early Onset Primary Ciliary Dyskinesia Lung Disease
NCT00739817	Not specified	UNKNOWN	Screening for Primary Ciliary Dyskinesia Using Nasal Nitric Oxide
NCT00783887	Not specified	COMPLETED	Diagnosis of Primary Ciliary Dyskinesia
NCT00807482	Not specified	RECRUITING	Pathogenesis of Primary Ciliary Dyskinesia (PCD) Lung Disease
NCT01070914	Not specified	UNKNOWN	Early Detection and Characterization of Primary Ciliary Dyskinesia
NCT01155115	Not specified	COMPLETED	Inflammatory and Microbiologic Markers in Sputum: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia
NCT01246258	Not specified	COMPLETED	Otolith Function in Patients With Primary Ciliary Dyskinesia
NCT01929356	Not specified	RECRUITING	Chest Physiotherapy and Lung Function in Primary Ciliary Dyskinesia
NCT02389049	Not specified	COMPLETED	Genetics of Primary Ciliary Dyskinesia
NCT02419365	Not specified	RECRUITING	International Primary Ciliary Dyskinesia (PCD) Registry
NCT02699177	Not specified	UNKNOWN	In Vivo Measurements of Nasal Ciliary Beat Frequency by Using Interferometry