CCDC40

Summary

CCDC40 (coiled-coil domain 40 molecular ruler complex subunit, HGNC:26090) is a protein-coding gene on chromosome 17q25.3, encoding Coiled-coil domain-containing protein 40 (Q4G0X9). 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.

This gene encodes a protein that is necessary for motile cilia function. It functions in correct left-right axis formation by regulating the assembly of the inner dynein arm and the dynein regulatory complexes, which control ciliary beat. Mutations in this gene cause ciliary dyskinesia type 15, a disorder due to defects in cilia motility. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55036 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary ciliary dyskinesia 15 (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 1,203 total — 76 pathogenic, 29 likely-pathogenic
• Phenotypes (HPO): 57
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_017950

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26090
Approved symbol	CCDC40
Name	coiled-coil domain 40 molecular ruler complex subunit
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20753, KIAA1640, FLJ32021, CILD15, FAP172, CFAP172
Ensembl gene	ENSG00000141519
Ensembl biotype	protein_coding
OMIM	613799
Entrez	55036

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 8 protein_coding, 6 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000269318, ENST00000374876, ENST00000374877, ENST00000397545, ENST00000571028, ENST00000572083, ENST00000572253, ENST00000572270, ENST00000573474, ENST00000573903, ENST00000574099, ENST00000574799, ENST00000574933, ENST00000575431, ENST00000576033, ENST00000576241, ENST00000897784

RefSeq mRNA: 3 — MANE Select: NM_017950 NM_001243342, NM_001330508, NM_017950

CCDS: CCDS42395, CCDS58604, CCDS82212

Canonical transcript exons

ENST00000397545 — 20 exons

Exon	Start	End
ENSE00000949408	80047279	80047402
ENSE00001464947	80036642	80036691
ENSE00001845941	80099527	80100613
ENSE00003483966	80086003	80086216
ENSE00003492401	80050064	80050283
ENSE00003502684	80058858	80058980
ENSE00003517307	80088011	80088102
ENSE00003518887	80049906	80049989
ENSE00003521199	80097245	80097403
ENSE00003550679	80065485	80065606
ENSE00003558823	80081546	80081789
ENSE00003559085	80081876	80082058
ENSE00003569505	80089764	80089884
ENSE00003579162	80048583	80048761
ENSE00003583120	80058494	80058651
ENSE00003604030	80087607	80087776
ENSE00003613155	80038123	80038186
ENSE00003616891	80095263	80095451
ENSE00003646098	80084743	80084988
ENSE00003684590	80039812	80040270

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 98.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.5660 / max 61.8116, expressed in 1007 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163204	2.5660	1007

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.50	gold quality
bronchial epithelial cell	CL:0002328	93.75	gold quality
sural nerve	UBERON:0015488	90.27	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.87	gold quality
left testis	UBERON:0004533	86.94	gold quality
tendon of biceps brachii	UBERON:0008188	86.76	gold quality
epithelium of bronchus	UBERON:0002031	86.69	gold quality
bronchus	UBERON:0002185	86.39	gold quality
adenohypophysis	UBERON:0002196	86.20	gold quality
right testis	UBERON:0004534	86.09	gold quality
pituitary gland	UBERON:0000007	85.75	gold quality
metanephros cortex	UBERON:0010533	85.49	gold quality
testis	UBERON:0000473	84.06	gold quality
stromal cell of endometrium	CL:0002255	83.30	gold quality
left uterine tube	UBERON:0001303	81.53	gold quality
left lobe of thyroid gland	UBERON:0001120	81.39	gold quality
mucosa of paranasal sinus	UBERON:0005030	81.20	gold quality
ventricular zone	UBERON:0003053	81.16	gold quality
thyroid gland	UBERON:0002046	80.69	gold quality
body of uterus	UBERON:0009853	80.52	gold quality
endocervix	UBERON:0000458	80.27	gold quality
right lobe of thyroid gland	UBERON:0001119	80.06	gold quality
buccal mucosa cell	CL:0002336	79.90	gold quality
caput epididymis	UBERON:0004358	79.75	gold quality
right lung	UBERON:0002167	79.14	gold quality
apex of heart	UBERON:0002098	78.97	gold quality
lower esophagus muscularis layer	UBERON:0035833	78.91	gold quality
lower esophagus	UBERON:0013473	78.80	gold quality
vena cava	UBERON:0004087	78.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.54	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting CCDC40, 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-6867-5P	100.00	82.21	3464
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-758-3P	98.42	68.60	1122
HSA-MIR-4669	97.94	62.71	224
HSA-MIR-634	97.74	67.11	818
HSA-MIR-6818-5P	97.50	67.10	1167
HSA-MIR-194-3P	97.36	65.96	1027
HSA-MIR-6849-3P	97.25	64.57	1371
HSA-MIR-1233-3P	96.81	65.44	573
HSA-MIR-3657	96.33	66.29	608
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-4654	95.86	65.72	751
HSA-MIR-6775-3P	95.76	65.91	982
HSA-MIR-4769-5P	95.37	66.09	570
HSA-MIR-3622B-5P	94.62	64.58	835
HSA-MIR-6808-3P	94.13	65.24	516
HSA-MIR-6767-3P	93.99	66.01	204

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 9)

• CCDC40 mutations in humans result in a variant of primary ciliary dyskinesia characterized by misplacement of the central pair of microtubules and defective assembly of inner dynein arms and dynein regulatory complexes. (PMID:21131974)
• 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 ccdc40. (PMID:25493340)
• Results identified a novel mutant alleles in CCDC40 gene, which altered the protein sequence and resulted in the ultrastructural defects in the microtubule structure of cilia suggesting that CCDC40 mutation may be a cause for ciliary dyskinesia. (PMID:25619595)
• A novel mutation causing primary ciliary dyskinesia was found in Japanese patients. (PMID:28939216)
• Clinical and genetic spectrum in 33 Egyptian families with suspected primary ciliary dyskinesia. (PMID:31650533)
• CCDC40 mutation as a cause of infertility in a Chinese family with primary ciliary dyskinesia. (PMID:34941110)
• 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	ccdc40	ENSDARG00000100584
mus_musculus	Ccdc40	ENSMUSG00000039963
rattus_norvegicus	Ccdc40	ENSRNOG00000059401
drosophila_melanogaster	l(2)41Ab	FBGN0262123

Protein

Protein identifiers

Coiled-coil domain-containing protein 40 — Q4G0X9 (reviewed: Q4G0X9)

All UniProt accessions (5): Q4G0X9, I3L292, I3L2X6, I3L3G6, I3L477

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 CCDC39 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. Required for axonemal recruitment of CCDC39.

Subcellular location. Cytoplasm. Cell projection. Cilium.

Disease relevance. Ciliary dyskinesia, primary, 15 (CILD15) [MIM:613808] 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.

Similarity. Belongs to the CCDC40 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q4G0X9-1	1	yes
Q4G0X9-2	2
Q4G0X9-3	3
Q4G0X9-4	4
Q4G0X9-5	5

RefSeq proteins (3): NP_001230271, NP_001317437, NP_060420* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR037386	CCDC40	Family

Pfam: PF08647

UniProt features (35 total): sequence conflict 13, splice variant 8, coiled-coil region 5, compositionally biased region 4, region of interest 2, chain 1, modified residue 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-Q4G0X9-F1	71.70	0.24

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 (1): 252

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 220 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_PANCREAS_DEVELOPMENT, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_INNER_DYNEIN_ARM_ASSEMBLY, GOBP_DIGESTIVE_SYSTEM_DEVELOPMENT, GOBP_AXONEMAL_DYNEIN_COMPLEX_ASSEMBLY, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EMBRYONIC_HEART_TUBE_DEVELOPMENT, GOBP_EMBRYONIC_ORGAN_MORPHOGENESIS, GOBP_HEART_MORPHOGENESIS, GOBP_CILIUM_ORGANIZATION

GO Biological Process (17): heart looping (GO:0001947), cilium movement (GO:0003341), epithelial cilium movement involved in extracellular fluid movement (GO:0003351), regulation of cilium beat frequency (GO:0003356), flagellated sperm motility (GO:0030317), lung development (GO:0030324), axoneme assembly (GO:0035082), determination of pancreatic left/right asymmetry (GO:0035469), inner dynein arm assembly (GO:0036159), motile cilium assembly (GO:0044458), cilium organization (GO:0044782), epithelial cilium movement involved in determination of left/right asymmetry (GO:0060287), protein localization to cilium (GO:0061512), axonemal dynein complex assembly (GO:0070286), determination of digestive tract left/right asymmetry (GO:0071907), determination of liver left/right asymmetry (GO:0071910), determination of left/right symmetry (GO:0007368)

GO Molecular Function (2): molecular_function (GO:0003674), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), cytoplasm (GO:0005737), cilium (GO:0005929), axoneme (GO:0005930), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
determination of left/right symmetry	4
cellular anatomical structure	4
cilium assembly	2
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
microtubule-based movement	1
cilium movement	1
extracellular transport	1
microtubule-based transport	1
regulation of cilium movement	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
microtubule bundle formation	1
cellular component assembly	1
pancreas development	1
axonemal dynein complex assembly	1
organelle organization	1
plasma membrane bounded cell projection organization	1
epithelial cilium movement involved in extracellular fluid movement	1
protein localization to organelle	1
axoneme assembly	1
protein-containing complex assembly	1
digestive tract development	1
liver development	1
determination of bilateral symmetry	1
left/right pattern formation	1
binding	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
cilium	1

Protein interactions and networks

STRING

1456 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC40	CCDC39	Q9UFE4	995
CCDC40	DRC1	Q96MC2	879
CCDC40	DRC2	Q8IXS2	867
CCDC40	RSPH4A	Q5TD94	830
CCDC40	DNAH5	Q8TE73	816
CCDC40	DNAAF1	Q8NEP3	813
CCDC40	DNAAF19	Q8IW40	813
CCDC40	DNAAF11	Q86X45	812
CCDC40	DNAI2	Q9GZS0	806
CCDC40	DNAH11	Q96DT5	804
CCDC40	DNAI1	Q9UI46	799
CCDC40	RSPH9	Q9H1X1	796
CCDC40	ODAD1	Q96M63	778
CCDC40	DNAAF3	Q8N9W5	776
CCDC40	ODAD2	Q5T2S8	756

IntAct

18 interactions, top by confidence:

A	B	Type	Score
IFT122	CDC7	psi-mi:“MI:0914”(association)	0.510
PACRG	CCDC40	psi-mi:“MI:0915”(physical association)	0.400
CCDC40	HNRNPC	psi-mi:“MI:0915”(physical association)	0.400
KRT38	KRBA1	psi-mi:“MI:0914”(association)	0.350
CCDC40	TRAF5	psi-mi:“MI:0914”(association)	0.350
BRK1	KIF5C	psi-mi:“MI:0914”(association)	0.350
	CCDC40	psi-mi:“MI:0915”(physical association)	0.000
VAPB	CCDC40	psi-mi:“MI:0915”(physical association)	0.000
DCAF7	CCDC40	psi-mi:“MI:0915”(physical association)	0.000
CENPH	CCDC40	psi-mi:“MI:0915”(physical association)	0.000
VAPA	CCDC40	psi-mi:“MI:0915”(physical association)	0.000
CCDC40	GTF2H2C	psi-mi:“MI:0915”(physical association)	0.000
CCDC40	TTC21B	psi-mi:“MI:0915”(physical association)	0.000
CCDC40	IFT43	psi-mi:“MI:0915”(physical association)	0.000
CCDC40	PACRG	psi-mi:“MI:0915”(physical association)	0.000
CCDC40	IFT122	psi-mi:“MI:0915”(physical association)	0.000
DISC1	CCDC40	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (53): TRAF5 (Affinity Capture-MS), ANKRD26 (Affinity Capture-MS), UNC13B (Affinity Capture-MS), CENPH (Affinity Capture-MS), HMMR (Affinity Capture-MS), VPS53 (Affinity Capture-MS), TNIP2 (Affinity Capture-MS), COG4 (Affinity Capture-MS), FAM83D (Affinity Capture-MS), STIM1 (Affinity Capture-MS), TMTC4 (Affinity Capture-MS), PSMC3 (Affinity Capture-MS), KIAA0319L (Affinity Capture-MS), CYTH2 (Affinity Capture-MS), CYTH1 (Affinity Capture-MS)

ESM2 similar proteins: A0JMY4, A2AJB1, A5D8V7, A6QQM8, A7MBH5, A7S8T5, B0BMJ2, F1RKB1, J3QPZ5, M1V4Y8, Q2T9W3, Q2TA16, Q32KY1, Q3SZX9, Q3USS3, Q3V079, Q494V2, Q4G0X9, Q4R7G7, Q4R7Y8, Q4R8V8, Q4V8F7, Q5JU67, Q5PQQ6, Q5SV66, Q5T5S1, Q5XI65, Q5XIJ8, Q6NTM6, Q6P5U8, Q7T0Y4, Q80VN0, Q80W32, Q8BI79, Q8BSN3, Q8C5T8, Q8C9J3, Q8CDV6, Q8IXS2, Q8NA47

Diamond homologs: Q4G0X9, Q56A40, Q8BI79

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1203 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	76
Likely pathogenic	29
Uncertain significance	465
Likely benign	360
Benign	131

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1065352	NM_017950.4(CCDC40):c.2832+489_2832+491dup	Pathogenic
1071463	NM_017950.4(CCDC40):c.1579del (p.Ala527fs)	Pathogenic
1076172	NM_017950.4(CCDC40):c.3349G>T (p.Glu1117Ter)	Pathogenic
1209988	NM_017950.4(CCDC40):c.1855C>T (p.Gln619Ter)	Pathogenic
1324026	NM_017950.4(CCDC40):c.2457del (p.Ile819fs)	Pathogenic
1344605	NM_017950.4(CCDC40):c.3358C>T (p.Gln1120Ter)	Pathogenic
1368509	NM_017950.4(CCDC40):c.901C>T (p.Arg301Ter)	Pathogenic
1390823	NM_017950.4(CCDC40):c.1225C>T (p.Gln409Ter)	Pathogenic
1452507	NM_017950.4(CCDC40):c.394_395del (p.Ser131_Val132insTer)	Pathogenic
1452881	NM_017950.4(CCDC40):c.783_784del (p.Arg261fs)	Pathogenic
1459089	NC_000017.10:g.(?78039264)(78039425_?)del	Pathogenic
1704380	NM_017950.4(CCDC40):c.798del (p.Ser267fs)	Pathogenic
1756199	NM_017950.4(CCDC40):c.1233dup (p.Arg412fs)	Pathogenic
1790829	NM_017950.4(CCDC40):c.2408del (p.Lys803fs)	Pathogenic
1797707	NM_017950.4(CCDC40):c.2920C>T (p.Gln974Ter)	Pathogenic
194774	NM_017950.4(CCDC40):c.2824_2825insCTGT (p.Arg942fs)	Pathogenic
2051445	NM_017950.4(CCDC40):c.2944dup (p.Asp982fs)	Pathogenic
2054714	NM_017950.4(CCDC40):c.390_391dup (p.Ser131fs)	Pathogenic
2129833	NM_017950.4(CCDC40):c.163del (p.Glu55fs)	Pathogenic
216117	NM_017950.4(CCDC40):c.3097A>T (p.Lys1033Ter)	Pathogenic
216118	NM_017950.4(CCDC40):c.961C>T (p.Arg321Ter)	Pathogenic
228326	NM_017950.4(CCDC40):c.940-2A>G	Pathogenic
241235	NM_017950.4(CCDC40):c.1620del (p.Ile541fs)	Pathogenic
241240	NM_017950.4(CCDC40):c.2852dup (p.Lys952fs)	Pathogenic
2431510	NM_017950.4(CCDC40):c.1266_1281dup (p.Glu428fs)	Pathogenic
2505169	NM_017950.4(CCDC40):c.2619+45G>A	Pathogenic
2505170	NM_017950.4(CCDC40):c.2236-213_2832+2269del	Pathogenic
2505511	NM_017950.4(CCDC40):c.967C>T (p.Gln323Ter)	Pathogenic
2720299	NM_017950.4(CCDC40):c.1741_1760del (p.Ser581fs)	Pathogenic
2747974	NM_017950.4(CCDC40):c.1696C>T (p.Gln566Ter)	Pathogenic

SpliceAI

3960 predictions. Top by Δscore:

Variant	Effect	Δscore
17:80038163:G:GT	donor_gain	1.0000
17:80039801:C:G	acceptor_gain	1.0000
17:80039802:A:AG	acceptor_gain	1.0000
17:80039803:C:G	acceptor_gain	1.0000
17:80039807:TACA:T	acceptor_loss	1.0000
17:80039809:C:G	acceptor_gain	1.0000
17:80039809:CA:C	acceptor_loss	1.0000
17:80039810:A:AG	acceptor_gain	1.0000
17:80039810:AG:A	acceptor_gain	1.0000
17:80039810:AGGT:A	acceptor_gain	1.0000
17:80039811:G:GA	acceptor_gain	1.0000
17:80039811:GG:G	acceptor_gain	1.0000
17:80039811:GGT:G	acceptor_gain	1.0000
17:80039811:GGTG:G	acceptor_gain	1.0000
17:80039811:GGTGT:G	acceptor_gain	1.0000
17:80040266:GATTG:G	donor_gain	1.0000
17:80047472:G:T	donor_gain	1.0000
17:80048581:A:AG	acceptor_gain	1.0000
17:80048581:AGT:A	acceptor_gain	1.0000
17:80048582:G:GG	acceptor_gain	1.0000
17:80048582:GTG:G	acceptor_gain	1.0000
17:80048742:T:TA	donor_gain	1.0000
17:80048743:G:GA	donor_gain	1.0000
17:80048762:G:GG	donor_gain	1.0000
17:80048767:G:GT	donor_gain	1.0000
17:80049904:A:AG	acceptor_gain	1.0000
17:80049905:G:GG	acceptor_gain	1.0000
17:80049986:GCTG:G	donor_gain	1.0000
17:80050059:TCCA:T	acceptor_loss	1.0000
17:80050061:CAGGT:C	acceptor_loss	1.0000

AlphaMissense

7555 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:80088098:G:C	A903P	0.993
17:80089801:G:C	A917P	0.993
17:80089780:T:A	W910R	0.991
17:80089780:T:C	W910R	0.991
17:80058877:T:C	L446P	0.990
17:80065485:G:C	A481P	0.989
17:80089799:T:C	L916P	0.988
17:80058628:G:C	A432P	0.987
17:80087772:T:C	L872P	0.987
17:80087676:T:C	L840P	0.986
17:80065539:T:A	W499R	0.983
17:80065539:T:C	W499R	0.983
17:80065570:G:C	R509P	0.980
17:80086100:T:C	L778P	0.979
17:80087685:T:C	L843P	0.978
17:80089787:A:T	K912I	0.978
17:80065541:G:C	W499C	0.977
17:80065541:G:T	W499C	0.977
17:80084909:G:C	R719P	0.977
17:80086109:A:C	Q781P	0.977
17:80088090:T:C	L900P	0.977
17:80089769:A:C	Q906P	0.977
17:80089778:T:C	L909P	0.977
17:80058650:A:C	Q439P	0.976
17:80089782:G:C	W910C	0.975
17:80089782:G:T	W910C	0.975
17:80086096:T:A	W777R	0.973
17:80086096:T:C	W777R	0.973
17:80086208:G:C	R814P	0.973
17:80099570:T:C	L1075P	0.973

dbSNP variants (sampled 300 via entrez): RS1000030766 (17:80091856 A>C), RS1000039494 (17:80051049 A>G), RS1000041281 (17:80097392 C>T), RS1000098547 (17:80046222 T>C,G), RS1000107267 (17:80063500 C>T), RS1000175559 (17:80077283 G>T), RS1000180694 (17:80036583 C>A,G,T), RS1000238092 (17:80070992 G>A), RS1000288694 (17:80082655 T>A), RS1000303943 (17:80052124 G>T), RS1000418951 (17:80096346 T>G), RS1000437541 (17:80087492 T>A,C,G), RS1000457262 (17:80052390 C>G,T), RS1000468581 (17:80087723 G>C), RS1000471972 (17:80061537 C>G)

Disease associations

OMIM: gene MIM:613799 | disease phenotypes: MIM:244400, MIM:613808, MIM:602723, MIM:608644, MIM:616638, MIM:243700, MIM:276900, MIM:232200

GenCC curated gene-disease

Disease	Classification	Inheritance
primary ciliary dyskinesia 15	Definitive	Autosomal recessive
primary ciliary dyskinesia	Supportive	Autosomal dominant
autoimmune disease	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
primary ciliary dyskinesia 15	Definitive	AR

Mondo (13): primary ciliary dyskinesia (MONDO:0016575), primary ciliary dyskinesia 15 (MONDO:0013435), psoriasis 2 (MONDO:0011269), pityriasis rubra pilaris (MONDO:0100017), primary ciliary dyskinesia 1 (MONDO:0009484), primary ciliary dyskinesia 3 (MONDO:0012085), male infertility (MONDO:0005372), macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome (MONDO:0014716), combined immunodeficiency due to DOCK8 deficiency (MONDO:0009478), glycogen storage disease II (MONDO:0009290), Usher syndrome (MONDO:0019501), disorder of glycogen metabolism (MONDO:0002412), autoimmune disease (MONDO:0007179)

Orphanet (9): Primary ciliary dyskinesia (Orphanet:244), Situs ambiguus (Orphanet:157769), Pityriasis rubra pilaris (Orphanet:2897), Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome (Orphanet:457485), Combined immunodeficiency due to DOCK8 deficiency (Orphanet:217390), Glycogen storage disease due to acid maltase deficiency (Orphanet:365), Usher syndrome (Orphanet:886), Glycogen storage disease (Orphanet:79201), Primary ciliary dyskinesia, Kartagener type (Orphanet:98861)

HPO phenotypes

57 total (30 of 57 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: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:0000789	Infertility
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:0004469	Chronic bronchitis
HP:0005301	Persistent left superior vena cava

GWAS associations

0 associations (top):

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D001327	Autoimmune Diseases	C20.111
D002925	Ciliary Motility Disorders	C08.200; C09.150; C16.131.077.245.500; C16.320.184.500
D006008	Glycogen Storage Disease	C16.320.565.202.449; C18.452.648.202.449
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430
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
D010916	Pityriasis Rubra Pilaris	C17.800.859.600.685
D052245	Usher Syndromes	C09.218.458.341.186.500.500; C09.218.458.341.887.886; C10.597.751.418.341.186.500.500; C10.597.751.418.341.887.886; C10.597.751.941.162.625.500; C11.768.585.658.500.813; C11.966.075.375.500; C16.131.077.299.500; C16.320.290.684.500; C23.888.592.763.393.341.887.886
C535278	Primary ciliary dyskinesia, 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression	2
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	decreases expression	1
aflatoxin B2	increases methylation	1
abrine	decreases expression	1
jinfukang	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	increases expression	1
Methotrexate	decreases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_VF21	UHOMi001-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001658	PHASE4	COMPLETED	Amoxicillin for the Treatment of Pediatric Autoimmune Disorders Associated With Streptococcal Infections
NCT00820469	PHASE4	COMPLETED	Study of the Influence of Plasma Exchange on the Pharmacokinetics of Rituximab
NCT00862693	PHASE4	UNKNOWN	Calcitriol in the Treatment of Immunoglobulin A Nephropathy
NCT01065285	PHASE4	COMPLETED	Vaccination Against Influenza in Autoimmune Diseases
NCT04015596	PHASE4	TERMINATED	Trial of Naproxen Sodium for the Treatment of OCD in Children With PANDAS
NCT04127747	PHASE4	UNKNOWN	Efficacy of Individualized Rituximab in Maintaining Remission of Moderate and Severe Systemic Lupus Erythematosus
NCT04297592	PHASE4	ENROLLING_BY_INVITATION	Antibiotic Prophylaxis in High-Risk Arthroplasty Patients
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT06723548	PHASE4	NOT_YET_RECRUITING	Telitacicept and Low-dose Steroids in Refractory Myasthenia Gravis
NCT06964269	PHASE4	RECRUITING	Use of Acthar Gel Single-Dose Pre-Filled SelfJectTM Injector in Patients With Moderate-Severe Keratitis and Autoimmune Disease
NCT00815633	PHASE4	TERMINATED	A Pilot Study of Alefacept for the Treatment of Pityriasis Rubra Pilaris
NCT07497620	PHASE4	NOT_YET_RECRUITING	Bimzelx (Bimekizumab) For The Treatment Of Adult Onset PRP
NCT02202382	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Male Infertility
NCT02204826	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study
NCT03802864	PHASE4	COMPLETED	Post-operative Pain Control of Testicular Sperm Extraction Using Liposomal Bupivacaine
NCT06100432	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Eurycoma Longifolia (DLBS5055) and Multivitamins (Vitamin C+Vitamin E+ β-carotene) for Infertile Males
NCT07523022	PHASE4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
NCT00455195	PHASE4	COMPLETED	Late-Onset Treatment Study Extension Protocol
NCT00483379	PHASE4	COMPLETED	High Dose or High Dose Frequency Study of Alglucosidase Alfa
NCT00486889	PHASE4	COMPLETED	Growth and Development Study of Alglucosidase Alfa
NCT00701129	PHASE4	COMPLETED	An Exploratory Study of the Safety and Efficacy of Prophylactic Immunomodulatory Treatment in Myozyme-naive Cross-Reacting Immunologic Material (CRIM[-]) Patients With Infantile-Onset Pompe Disease
NCT00701701	PHASE4	TERMINATED	Immune Tolerance Induction Study
NCT01288027	PHASE4	COMPLETED	Exploratory Muscle Biopsy Assessment Study in Patients With Late-Onset Pompe Disease Treated With Alglucosidase Alfa
NCT01410890	PHASE4	COMPLETED	Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease
NCT01526785	PHASE4	TERMINATED	A Study to Evaluate the Efficacy and Safety of Alglucosidase Alfa Produced at the 4000 L Scale for Pompe Disease
NCT01597596	PHASE4	TERMINATED	A Noninferiority Study of Alglucosidase Alfa Manufactured at the 160 L and 4000 L Scales in Treatment Naïve Patients With Infantile-Onset Pompe Disease
NCT02405598	PHASE4	COMPLETED	Evaluation of Salbutamol as an Adjuvant Therapy for Pompe Disease
NCT02405624	PHASE4	UNKNOWN	CPAP for Infantile Pompe Disease
NCT02525172	PHASE4	UNKNOWN	Immune Modulation Therapy for Pompe Disease
NCT03687333	PHASE4	COMPLETED	Evaluate Efficacy and Safety in Chinese Patients With Infantile-Onset Pompe Disease With One Year Alglucosidase Alfa Treatment
NCT05164055	PHASE4	ACTIVE_NOT_RECRUITING	Avalglucosidase Alfa French Post-trial Access for Participants With Pompe Disease (PTA Avalglucosidase)
NCT06575829	PHASE4	NOT_YET_RECRUITING	Treatment Frequency Reduction in Pompe Disease
NCT06666413	PHASE4	RECRUITING	China Post-approval Commitment (PAC) Study of Avalglucosidase Alfa in Participants With IOPD
NCT00001768	PHASE3	COMPLETED	Treatment of Childhood Onset Psychiatric Disorders With Intravenous Immunoglobulin (IVIg)
NCT00035308	PHASE3	COMPLETED	Safety and Efficacy Study of LJP 394 (Abetimus Sodium) to Treat Lupus Kidney Disease
NCT00351377	PHASE3	COMPLETED	Gastrointestinal and Health-related Quality of Life Outcomes in Patients With Autoimmune Diseases Treated With Mycophenolate
NCT00419419	PHASE3	COMPLETED	Phase III Study of a Topical Gel Formulation for Treatment and Prevention of Raynaud’s Phenomenon
NCT01004432	PHASE3	COMPLETED	Golimumab in Rheumatoid Arthritis Participants With an Inadequate Response to Etanercept (ENBREL) or Adalimumab (HUMIRA)
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus