DNAI1

Summary

DNAI1 (dynein axonemal intermediate chain 1, HGNC:2954) is a protein-coding gene on chromosome 9p13.3, encoding Dynein axonemal intermediate chain 1 (Q9UI46). Component of dynein, a family of motor proteins essential for movement along microtubules.

This gene encodes a member of the dynein intermediate chain family. The encoded protein is part of the dynein complex in respiratory cilia. The inner- and outer-arm dyneins, which bridge between the doublet microtubules in axonemes, are the force-generating proteins responsible for the sliding movement in axonemes. The intermediate and light chains, thought to form the base of the dynein arm, help mediate attachment and may also participate in regulating dynein activity. Mutations in this gene result in abnormal ciliary ultrastructure and function associated with primary ciliary dyskinesia and Kartagener syndrome. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 27019 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary ciliary dyskinesia 1 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 1,076 total — 79 pathogenic, 65 likely-pathogenic
• Phenotypes (HPO): 58
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_012144

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2954
Approved symbol	DNAI1
Name	dynein axonemal intermediate chain 1
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	DIC1, PCD, CILD1, oda6
Ensembl gene	ENSG00000122735
Ensembl biotype	protein_coding
OMIM	604366
Entrez	27019

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000242317, ENST00000437363, ENST00000442556, ENST00000470169, ENST00000470982, ENST00000485580, ENST00000488369, ENST00000488790, ENST00000614641, ENST00000878474, ENST00000878475, ENST00000878476

RefSeq mRNA: 2 — MANE Select: NM_012144 NM_001281428, NM_012144

CCDS: CCDS6557, CCDS75829

Canonical transcript exons

ENST00000242317 — 20 exons

Exon	Start	End
ENSE00001603830	34512109	34512198
ENSE00001606570	34501138	34501181
ENSE00001659762	34500722	34500839
ENSE00001661770	34514394	34514542
ENSE00001703008	34485142	34485240
ENSE00001732219	34513112	34513191
ENSE00001747680	34520658	34520984
ENSE00001782402	34512337	34512424
ENSE00002241195	34506627	34506874
ENSE00003499033	34514640	34514739
ENSE00003593359	34517285	34517467
ENSE00003613629	34485437	34485517
ENSE00003614900	34490369	34490488
ENSE00003621775	34490012	34490124
ENSE00003634876	34493194	34493328
ENSE00003654884	34491495	34491554
ENSE00003676718	34489323	34489449
ENSE00003677912	34483448	34483480
ENSE00003787850	34497115	34497199
ENSE00003849665	34458805	34459053

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 99.36.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5481 / max 171.4123, expressed in 383 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96512	0.9918	273
205465	0.3180	185
96513	0.2058	45
96514	0.0172	5
205466	0.0083	2
96515	0.0070	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.36	gold quality
bronchial epithelial cell	CL:0002328	96.92	gold quality
epithelium of bronchus	UBERON:0002031	96.81	gold quality
bronchus	UBERON:0002185	95.97	gold quality
left testis	UBERON:0004533	94.08	gold quality
right testis	UBERON:0004534	94.01	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.86	gold quality
adenohypophysis	UBERON:0002196	92.95	gold quality
pituitary gland	UBERON:0000007	91.54	gold quality
testis	UBERON:0000473	90.75	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.93	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.86	gold quality
sperm	CL:0000019	82.41	silver quality
right lung	UBERON:0002167	82.02	gold quality
nasal cavity epithelium	UBERON:0005384	81.30	gold quality
nucleus accumbens	UBERON:0001882	80.37	gold quality
caudate nucleus	UBERON:0001873	80.28	gold quality
left uterine tube	UBERON:0001303	78.37	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.24	gold quality
putamen	UBERON:0001874	77.40	gold quality
ventricular zone	UBERON:0003053	77.20	gold quality
epithelium of nasopharynx	UBERON:0001951	76.63	gold quality
nasopharynx	UBERON:0001728	76.62	gold quality
fallopian tube	UBERON:0003889	76.29	gold quality
metanephros cortex	UBERON:0010533	74.40	gold quality
nasal cavity mucosa	UBERON:0001826	74.30	gold quality
hypothalamus	UBERON:0001898	73.43	gold quality
trachea	UBERON:0003126	72.40	gold quality
amygdala	UBERON:0001876	72.07	gold quality
right frontal lobe	UBERON:0002810	70.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXJ1

miRNA regulators (miRDB)

23 targeting DNAI1, 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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-18A-5P	99.29	71.05	806
HSA-MIR-18B-5P	99.29	71.05	806
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-6881-5P	98.16	67.38	665
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-3649	96.85	64.10	340
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-6738-5P	96.33	63.61	815
HSA-MIR-4772-5P	95.60	68.04	617
HSA-MIR-1914-3P	95.07	63.37	762

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 8)

• A total of 10% of patients with PCD are estimated to harbor mutations in DNAI1; most occur as a common founder IVS1+2_3insT or in exons 13, 16, and 17. (PMID:16858015)
• DNAI1 gene mutation is not a common cause of primary ciliary dyskinesia. (PMID:18434704)
• Male carriers of the mutations always exhibit asthenozoospermia, whereas female carriers manifest no alterations in either fertility or pulmonary clearance. (PMID:18492703)
• Two dynein genes, encoding ODA intermediate chain (DNAI1) and heavy chain (DNAH5), have been seen to be mutated in approximately 30-38% of the families (PMID:19300264)
• The worldwide involvement of DNAI1 mutations in PCD pathogenesis in families not preselected for ODA defects ranges from 7 to 10%. (PMID:21143860)
• A novel mutation causing primary ciliary dyskinesia was found in Japanese patients. (PMID:28939216)
• Deep phenotyping, including quantitative ciliary beating parameters, and extensive genotyping in primary ciliary dyskinesia. (PMID:31772028)
• Identification and Classification of Novel Genetic Variants: En Route to the Diagnosis of Primary Ciliary Dyskinesia. (PMID:34445527)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnai1.2	ENSDARG00000038788
danio_rerio	dnai1.1	ENSDARG00000100081
mus_musculus	Dnai1	ENSMUSG00000061322
rattus_norvegicus	Dnai1	ENSRNOG00000013734
drosophila_melanogaster	CG9313	FBGN0034566

Paralogs (7): DYNC1I2 (ENSG00000077380), DYNC2I2 (ENSG00000119333), DYNC2I1 (ENSG00000126870), DNAI4 (ENSG00000152763), DYNC1I1 (ENSG00000158560), DNAI3 (ENSG00000162643), DNAI2 (ENSG00000171595)

Protein

Protein identifiers

Dynein axonemal intermediate chain 1 — Q9UI46 (reviewed: Q9UI46)

Alternative names: Axonemal dynein intermediate chain 1

All UniProt accessions (6): A0A087WWV9, A0A140VJI0, Q9UI46, H0Y6V0, H0YDT9, Q5T8G8

UniProt curated annotations — full annotation on UniProt →

Function. Component of dynein, a family of motor proteins essential for movement along microtubules. Required for structural and functional integrity of cilia. Part of the dynein complex of respiratory cilia.

Subunit / interactions. Dynein consists of at least two heavy chains and a number of intermediate and light chains. Part of the ciliary outer dynein arms (ODAs), at least consisting of dynein axonemal heavy chains, light chains and intermediate chains. The ODAs interact with DNAAF9; this interaction inactivates the dyneins. Interacts with BICD2. Interacts with CFAP45 and CFAP52. Interacts with CFAP53. Interacts with CFAP70 and DNAI2.

Subcellular location. Dynein axonemal particle. Cytoplasm. Cytoskeleton. Cilium axoneme. Cell projection. Cilium. Flagellum.

Tissue specificity. Expressed in respiratory ciliated cells (at protein level).

Disease relevance. Ciliary dyskinesia, primary, 1 (CILD1) [MIM:244400] 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. Kartagener syndrome (KTGS) [MIM:244400] An autosomal recessive disorder characterized by the association of primary ciliary dyskinesia with situs inversus. Clinical features include recurrent respiratory infections, bronchiectasis, infertility, and lateral transposition of the viscera of the thorax and abdomen. The situs inversus is most often total, although it can be partial in some cases (isolated dextrocardia or isolated transposition of abdominal viscera). The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the dynein intermediate chain family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UI46-1	1	yes
Q9UI46-2	2

RefSeq proteins (2): NP_001268357, NP_036276* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR050687	Dynein_IC	Family

Pfam: PF00400

UniProt features (22 total): repeat 7, sequence variant 6, modified residue 2, splice variant 2, sequence conflict 2, region of interest 2, chain 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-Q9UI46-F1	79.54	0.50

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): 131, 134

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 265 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, AACYNNNNTTCCS_UNKNOWN, AP2_Q3, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_SPECIFICATION_OF_SYMMETRY, PAX8_B, GOBP_AXONEMAL_DYNEIN_COMPLEX_ASSEMBLY, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_RESPONSE_TO_INSULIN, BRN2_01, TGCTGAY_UNKNOWN, GOBP_CILIUM_ORGANIZATION

GO Biological Process (8): cilium movement (GO:0003341), epithelial cilium movement involved in extracellular fluid movement (GO:0003351), determination of left/right symmetry (GO:0007368), heart development (GO:0007507), insulin receptor signaling pathway (GO:0008286), flagellated sperm motility (GO:0030317), outer dynein arm assembly (GO:0036158), cell projection organization (GO:0030030)

GO Molecular Function (4): cytoskeletal motor activity (GO:0003774), dynein light chain binding (GO:0045503), dynein heavy chain binding (GO:0045504), protein binding (GO:0005515)

GO Cellular Component (13): extracellular region (GO:0005576), centrosome (GO:0005813), cytoskeleton (GO:0005856), microtubule (GO:0005874), cilium (GO:0005929), outer dynein arm (GO:0036157), glial cell projection (GO:0097386), 9+2 motile cilium (GO:0097729), dynein axonemal particle (GO:0120293), cytoplasm (GO:0005737), microtubule cytoskeleton (GO:0015630), dynein complex (GO:0030286), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein binding	2
intracellular membraneless organelle	2
plasma membrane bounded cell projection	2
microtubule-based movement	1
cilium movement	1
extracellular transport	1
microtubule-based transport	1
determination of bilateral symmetry	1
left/right pattern formation	1
animal organ development	1
circulatory system development	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
axonemal dynein complex assembly	1
cellular component organization	1
molecular_function	1
binding	1
centriole	1
microtubule organizing center	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
intraciliary transport particle	1
membrane-bounded organelle	1
axonemal dynein complex	1
radial spoke	1
motile cilium	1
inner dynein arm	1
outer dynein arm	1
axonemal central pair	1
axonemal doublet microtubule	1
cytoplasm	1
intracellular anatomical structure	1
cytoskeleton	1
microtubule associated complex	1
catalytic complex	1

Protein interactions and networks

STRING

1222 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAI1	DNAH5	Q8TE73	983
DNAI1	DNAH11	Q96DT5	975
DNAI1	DNAAF2	Q9NVR5	958
DNAI1	RSPH4A	Q5TD94	950
DNAI1	RSPH9	Q9H1X1	949
DNAI1	NME8	Q8N427	939
DNAI1	DNAAF1	Q8NEP3	939
DNAI1	DNALI1	O14645	825
DNAI1	ODAD1	Q96M63	806
DNAI1	CCDC39	Q9UFE4	802
DNAI1	CCDC40	Q4G0X9	799
DNAI1	RPGR	Q92834	798
DNAI1	DNAAF11	Q86X45	792
DNAI1	DNAH9	Q9NYC9	780
DNAI1	DNAAF19	Q8IW40	780

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ATG16L1		psi-mi:“MI:0914”(association)	0.350
DNAI1	ESPN	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): SQSTM1 (Affinity Capture-Western), DNAI1 (Reconstituted Complex), HIF1A (Affinity Capture-Western), HSPA8 (Affinity Capture-MS), ESPN (Affinity Capture-MS), ZNF318 (Affinity Capture-MS), DNAI1 (Affinity Capture-MS), DNAI1 (Proximity Label-MS), STRN3 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2AC93, B2RY71, E7F6H7, E9PYY5, E9Q5M6, O14576, O43815, O55106, O88485, O88487, P27766, P36872, P70483, Q0III3, Q13409, Q13610, Q16959, Q16960, Q29RQ3, Q2HJ56, Q32KS2, Q32LP9, Q4QR00, Q4V8G4, Q5DQR4, Q5NVM2, Q5SQE2, Q5VTH9, Q5XIL8, Q5ZLK1, Q62871, Q63100, Q66HC9, Q6GPB9, Q8BPM2, Q8C0M8, Q8C0P5, Q8IVH8, Q8IWG1, Q92828

Diamond homologs: E9PYY5, F1QHZ6, Q16959, Q32KS2, Q39578, Q4V8G4, Q5VTH9, Q5XIL8, Q6GPB9, Q8C0M8, Q9UI46, Q54ED4, Q55C80, A4R2Q6, A8IZG4, G0SA60, O94244, Q04225, Q0UNA9, Q1JQD2, Q29RH4, Q2GSM6, Q4I7L0, Q4P553, Q54YD8, Q5XI13, Q6BLS5, Q6H8D5, Q6H8D6, Q810D6, Q8L828, Q8VE80, Q96J01, Q9BQ67, Q9C827, Q9CAA0, Q9P783, Q9USR0, Q9ZUN8, Q4QR85

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FOXJ1	“up-regulates quantity by expression”	DNAI1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

1076 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	79
Likely pathogenic	65
Uncertain significance	288
Likely benign	528
Benign	26

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1067969	NM_012144.4(DNAI1):c.1490G>T (p.Gly497Val)	Pathogenic
1071038	NM_012144.4(DNAI1):c.146_149del (p.Val49fs)	Pathogenic
1071319	NM_012144.4(DNAI1):c.1358_1359del (p.Ser453fs)	Pathogenic
1072135	NM_012144.4(DNAI1):c.458T>A (p.Leu153Ter)	Pathogenic
1075263	NM_012144.4(DNAI1):c.1127del (p.Pro376fs)	Pathogenic
1076070	NM_012144.4(DNAI1):c.859G>T (p.Glu287Ter)	Pathogenic
1076692	NM_012144.4(DNAI1):c.688_689del (p.Ile230fs)	Pathogenic
1184556	NM_012144.4(DNAI1):c.565_566del (p.Leu188_Thr189insTer)	Pathogenic
1343809	NM_012144.4(DNAI1):c.1871del (p.Pro624fs)	Pathogenic
1365696	NM_012144.4(DNAI1):c.264del (p.Gly89fs)	Pathogenic
1372407	NM_012144.4(DNAI1):c.1202dup (p.Gly402fs)	Pathogenic
1372912	NM_012144.4(DNAI1):c.465_466del (p.Glu156fs)	Pathogenic
1395381	NM_012144.4(DNAI1):c.663_664del (p.Ala223fs)	Pathogenic
1435836	NM_012144.4(DNAI1):c.1569+1G>A	Pathogenic
1437225	NM_012144.4(DNAI1):c.1887del (p.Asn630fs)	Pathogenic
1456764	NM_012144.4(DNAI1):c.1191_1193del (p.Tyr397_Leu398delinsTer)	Pathogenic
1459390	NC_000009.11:g.(?34513100)(34514747_?)del	Pathogenic
1731355	NM_012144.4(DNAI1):c.342del (p.Ser115fs)	Pathogenic
1990327	NM_012144.4(DNAI1):c.1498_1502del (p.Thr500fs)	Pathogenic
2008295	NM_012144.4(DNAI1):c.92C>G (p.Ser31Ter)	Pathogenic
2012973	NM_012144.4(DNAI1):c.718A>T (p.Lys240Ter)	Pathogenic
2014988	NM_012144.4(DNAI1):c.402_403insAT (p.Val135fs)	Pathogenic
2022304	NM_012144.4(DNAI1):c.43A>T (p.Lys15Ter)	Pathogenic
2026405	NM_012144.4(DNAI1):c.-1_4del (p.Met1fs)	Pathogenic
2030571	NM_012144.4(DNAI1):c.1134C>G (p.Tyr378Ter)	Pathogenic
2075089	NM_012144.4(DNAI1):c.484_485del (p.Asp162fs)	Pathogenic
2106380	NM_012144.4(DNAI1):c.864del (p.Met289fs)	Pathogenic
2116429	NM_012144.4(DNAI1):c.947dup (p.Thr318fs)	Pathogenic
2126586	NM_012144.4(DNAI1):c.1720_1725delinsTGATAGGAATAAGGGCTAAATGCAGGAAAGGGGATGGAGAATCTAGAGGGTGACTTTAGCCCAGCTCAGCATCTTTTCCTCCGGGCCCTCCCTCCCTTCCTGGGAGTTGAGGTAGAAGGGGGGATTCGGAGGAGTTAGAATATTTTGGGAAAACTTCCTGGAGGAGATTTGTACTTGAGCTGAGCTTGGAAGGCCAGAATTATCTCTGAATACTGGGTACATCCCAGCCAGCAGGATGGAACCTCACGGTCAGTTTCTACACA (p.Thr574_Pro575delinsTer)	Pathogenic
2136544	NM_012144.4(DNAI1):c.1289_1310dup (p.Val438fs)	Pathogenic

SpliceAI

3999 predictions. Top by Δscore:

Variant	Effect	Δscore
9:34483479:GA:G	donor_gain	1.0000
9:34483481:G:GG	donor_gain	1.0000
9:34485136:GTCTA:G	acceptor_loss	1.0000
9:34485137:TCTAG:T	acceptor_loss	1.0000
9:34485138:CTAG:C	acceptor_loss	1.0000
9:34485139:TA:T	acceptor_loss	1.0000
9:34485241:GTGA:G	donor_gain	1.0000
9:34485245:G:GG	donor_gain	1.0000
9:34485436:GGA:G	acceptor_gain	1.0000
9:34485518:G:GG	donor_gain	1.0000
9:34489320:TA:T	acceptor_loss	1.0000
9:34489321:A:T	acceptor_loss	1.0000
9:34489322:G:GC	acceptor_loss	1.0000
9:34489322:GGAA:G	acceptor_gain	1.0000
9:34489447:C:T	donor_gain	1.0000
9:34489447:CAGG:C	donor_loss	1.0000
9:34489448:AG:A	donor_loss	1.0000
9:34489449:GG:G	donor_loss	1.0000
9:34489450:G:GA	donor_loss	1.0000
9:34489451:T:G	donor_loss	1.0000
9:34490364:TTCA:T	acceptor_loss	1.0000
9:34490365:TCA:T	acceptor_loss	1.0000
9:34490366:CA:C	acceptor_loss	1.0000
9:34490367:A:AC	acceptor_loss	1.0000
9:34490368:GGC:G	acceptor_gain	1.0000
9:34490368:GGCA:G	acceptor_gain	1.0000
9:34490421:A:T	donor_gain	1.0000
9:34490451:G:GG	donor_gain	1.0000
9:34490542:G:T	donor_gain	1.0000
9:34514392:A:AG	acceptor_gain	1.0000

AlphaMissense

4657 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:34514503:G:T	S560I	0.999
9:34514526:T:A	W568R	0.999
9:34514526:T:C	W568R	0.999
9:34514689:T:A	W590R	0.999
9:34514689:T:C	W590R	0.999
9:34490441:T:C	F192L	0.998
9:34490443:C:A	F192L	0.998
9:34490443:C:G	F192L	0.998
9:34514497:C:T	S558F	0.998
9:34514502:A:C	S560R	0.998
9:34514504:C:A	S560R	0.998
9:34514504:C:G	S560R	0.998
9:34514508:G:C	D562H	0.998
9:34485459:G:C	R68P	0.997
9:34485465:T:C	L70S	0.997
9:34500787:T:A	W323R	0.997
9:34500787:T:C	W323R	0.997
9:34512115:T:A	W440R	0.997
9:34512115:T:C	W440R	0.997
9:34513166:G:A	G515D	0.997
9:34513178:G:T	G519V	0.997
9:34514466:T:A	W548R	0.997
9:34514466:T:C	W548R	0.997
9:34514471:C:A	N549K	0.997
9:34514471:C:G	N549K	0.997
9:34514496:T:C	S558P	0.997
9:34517406:G:A	G647D	0.997
9:34485230:T:C	L57S	0.996
9:34490447:T:C	F194L	0.996
9:34490449:C:A	F194L	0.996

dbSNP variants (sampled 300 via entrez): RS1000077379 (9:34464134 G>A), RS1000088231 (9:34479068 G>A), RS1000131997 (9:34509486 T>A), RS1000161908 (9:34468530 TAAA>T,TAA), RS1000210979 (9:34478247 G>A), RS1000298619 (9:34461317 A>G), RS1000321423 (9:34471474 G>A), RS1000369311 (9:34457727 T>C), RS1000408460 (9:34475384 A>G), RS1000459884 (9:34461574 A>T), RS1000518988 (9:34477087 C>T), RS1000599024 (9:34521114 T>G), RS1000600239 (9:34513030 G>A), RS1000635280 (9:34482141 G>A,C), RS1000730619 (9:34505811 TAGCCTTCCACCTCTCC>T)

Disease associations

OMIM: gene MIM:604366 | disease phenotypes: MIM:244400

GenCC curated gene-disease

Disease	Classification	Inheritance
primary ciliary dyskinesia 1	Strong	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 1	Definitive	AR

Mondo (4): primary ciliary dyskinesia 1 (MONDO:0009484), primary ciliary dyskinesia (MONDO:0016575), infertility disorder (MONDO:0005047), male infertility (MONDO:0005372)

Orphanet (2): Primary ciliary dyskinesia (Orphanet:244), Primary ciliary dyskinesia, Kartagener type (Orphanet:98861)

HPO phenotypes

58 total (30 of 58 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:0000458	Anosmia
HP:0000481	Abnormal cornea morphology
HP:0000510	Rod-cone dystrophy
HP:0000750	Delayed speech and language development
HP:0000924	Abnormality of the skeletal system
HP:0001217	Clubbing
HP:0001334	Communicating hydrocephalus
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:0002090	Pneumonia
HP:0002110	Bronchiectasis
HP:0002119	Ventriculomegaly
HP:0002257	Chronic rhinitis
HP:0002315	Headache
HP:0002566	Intestinal malrotation
HP:0002643	Neonatal respiratory distress
HP:0002688	Absent frontal sinuses

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010993_1	Anti-drug antibodies in autoimmune disease (time to event)	5.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010559	anti-drug antibody measurement

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
D007246	Infertility	C12.100.750
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

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	3
Cadmium Chloride	decreases expression, increases abundance	2
propionaldehyde	increases expression	1
2,3-pentanedione	decreases expression	1
sodium arsenite	increases expression	1
aflatoxin B2	increases methylation	1
entinostat	increases expression	1
abrine	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Cadmium	increases abundance, decreases expression	1
Diacetyl	decreases expression	1
Smoke	increases abundance, increases expression	1
Testosterone	decreases expression	1
Acrylamide	decreases expression	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_D3BF	PCD2	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

298 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
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
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
NCT00975117	PHASE3	COMPLETED	Spermotrend in the Treatment of Male Infertility
NCT01407432	PHASE3	COMPLETED	Impact of Folates in the Care of the Male Infertility
NCT01895816	PHASE3	COMPLETED	Herbal Tonic Fertile Supplement(ZO2C5)
NCT02605070	PHASE3	TERMINATED	Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
NCT07402759	PHASE3	ACTIVE_NOT_RECRUITING	Impact of tdrd9 Gene Mutations in the Therapeutic Response to L-carnitine in Oligoasthenozoospermic Men
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
NCT01880086	PHASE2	COMPLETED	Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
NCT02061384	PHASE2	COMPLETED	RA-2 13-cis Retinoic Acid (Isotretinoin)
NCT02421887	PHASE2	COMPLETED	Males, Antioxidants, and Infertility Trial
NCT05200663	PHASE2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
NCT05290558	PHASE2	ACTIVE_NOT_RECRUITING	The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial
NCT06091969	PHASE2	NOT_YET_RECRUITING	Supplementation for Male Subfertility
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
NCT01595308	PHASE1	COMPLETED	A Pilot Study to Evaluate the Effect of Pomegranate Juice on Semen Parameters in Healthy Male Volunteers
NCT02122211	PHASE1	COMPLETED	Choline Dehydrogenase and Sperm Function: Effects of Betaine