DNAI2 (dynein axonemal intermediate chain 2)

Gene

• Entrez ID: 64446
• Gene name: Dynein axonemal intermediate chain 2
• Gene symbol: DNAI2
• Synonyms (NCBI Gene): CILD9, DIC2, oda6
• Chromosome: 17
• Chromosome location: 17q25.1
• Summary: The protein encoded by this gene belongs to the dynein intermediate chain family, and is part of the dynein complex of respiratory cilia and sperm flagella. Mutations in this gene are associated with primary ciliary dyskinesia type 9. Alternatively splice

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs137852998	C>G,T	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant, missense variant
rs139935771	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant, non coding transcript variant
rs140326154	G>A	Conflicting-interpretations-of-pathogenicity, benign	Coding sequence variant, non coding transcript variant, missense variant
rs200708870	C>T	Pathogenic	Non coding transcript variant, stop gained, coding sequence variant
rs397515358	T>G	Pathogenic	Intron variant
rs397515565	G>A,C,T	Pathogenic	Splice donor variant
rs752924362	G>A,C	Pathogenic, pathogenic-likely-pathogenic	Coding sequence variant, stop gained, missense variant, non coding transcript variant
rs756868374	C>T	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs758109864	G>A	Likely-pathogenic	Splice donor variant
rs770946088	C>A	Pathogenic	Stop gained, non coding transcript variant, coding sequence variant
rs780116486	C>T	Pathogenic	Intron variant, non coding transcript variant, stop gained, coding sequence variant
rs878855078	G>A,C	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1060502202	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs1240172375	G>-	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs1555614910	->G	Pathogenic	Frameshift variant, intron variant, non coding transcript variant, coding sequence variant
rs1598278059	G>A	Likely-pathogenic	Splice acceptor variant
rs1598293348	A>-	Likely-pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant, intron variant
rs1598330492	A>T	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs1598342751	AC>CATT	Pathogenic	Frameshift variant, coding sequence variant, non coding transcript variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003341	Process	Cilium movement	IBA
GO:0003341	Process	Cilium movement	IMP	18950741, 23261302
GO:0003777	Function	Microtubule motor activity	IMP	11153919
GO:0005515	Function	Protein binding	IPI	25232951, 28176794
GO:0005737	Component	Cytoplasm	IEA
GO:0005856	Component	Cytoskeleton	IEA
GO:0005858	Component	Axonemal dynein complex	IMP	11153919
GO:0005874	Component	Microtubule	IEA
GO:0005929	Component	Cilium	IEA
GO:0005930	Component	Axoneme	IDA	18950741, 23849778
GO:0005930	Component	Axoneme	IEA
GO:0005930	Component	Axoneme	IMP	11153919
GO:0007368	Process	Determination of left/right symmetry	IMP	18950741
GO:0009897	Component	External side of plasma membrane	IEA
GO:0030030	Process	Cell projection organization	IEA
GO:0030286	Component	Dynein complex	IEA
GO:0036126	Component	Sperm flagellum	IDA	18950741
GO:0036157	Component	Outer dynein arm	IBA
GO:0036157	Component	Outer dynein arm	IMP	18950741
GO:0036158	Process	Outer dynein arm assembly	IBA
GO:0036158	Process	Outer dynein arm assembly	IMP	18950741, 23261302
GO:0042995	Component	Cell projection	IEA
GO:0045503	Function	Dynein light chain binding	IBA
GO:0045504	Function	Dynein heavy chain binding	IBA
GO:0060271	Process	Cilium assembly	IMP	11153919
GO:0097386	Component	Glial cell projection	IEA
GO:0097729	Component	9+2 motile cilium	IEA
GO:0120293	Component	Dynein axonemal particle	IEA
GO:0120293	Component	Dynein axonemal particle	ISS

Other IDs

• MIM: 605483
• HGNC: 18744
• e!Ensembl: ENSG00000171595

Protein

• UniProt ID: Q9GZS0
• Protein name: Dynein axonemal intermediate chain 2 (Axonemal dynein intermediate chain 2)
• Protein function: Part of the dynein complex of respiratory cilia.
• PDB: 8J07
• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in trachea and testis. Expressed in respiratory ciliated cells (at protein level) (PubMed:33139725). {ECO:0000269|PubMed:33139725}.
• Sequence:

  MEIVYVYVKKRSEFGKQCNFSDRQAELNIDIMPNPELAEQFVERNPVDTGIQCSISMSEH
  EANSERFEMETRGVNHVEGGWPKDVNPLELEQTIRFRKKVEKDENYVNAIMQLGSIMEHC
  IKQNNAIDIYEEYFNDEEAMEVMEEDPSAKTINVFRDPQEIKRAATHLSWHPDGNRKLAV
  AYSCLDFQRAPVGMSSDSYIWDLENPNKPELALKPSSPLVTLEFNPKDSHVLLGGCYNGQ
  IACWDTRKGSLVAELSTIESSHRDPVYGTIWLQSKTGTECFSASTDGQVMWWDIRKMSEP
  TEVVILDITKKEQLENALGAISLEFESTLPTKFMVGTEQGIVISCNRKAKTSAEKIVCTF
  PGHHGPIYALQRNPFYPKNFLTVGDWTARIWSEDSRESSIMWTKYHMAYLTDAAWSPVRP
  TVFFTTRMDGTLDIWDFMFEQCDPTLSLKVCDEALFCLRVQDNGCLIACGSQLGTTTLLE
  VSPGLSTLQRNEKNVASSMFERETRREKILEARHREMRLKEKGKAEGRDEEQTDEELAVD
  LEALVSKAEEEFFDIIFAELKKKEADAIKLTPVPQQPSPEEDQVVEEGEEAAGEEGDEEV
  EEDLA

• Sequence length: 605

Pathways

KEGG:

Motor proteins
Amyotrophic lateral sclerosis
Huntington disease
Pathways of neurodegeneration - multiple diseases

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
DNAI2-related disorder	Likely pathogenic; Pathogenic	rs1442078154, rs141581673	RCV003406223 RCV004754437	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Primary ciliary dyskinesia	Likely pathogenic; Pathogenic	rs2143940594, rs764381446, rs769251936, rs2144026301, rs545536618, rs2144112404, rs755060592, rs2144105381, rs745755917, rs1374403931, rs2144035068, rs1567875399, rs776777011, rs397515565, rs755714858, rs751056551, rs2144112583, rs2144113081, rs2144077639, rs2143903171, rs2509762743, rs2053123483, rs2509766413, rs1567840448, rs2509752143, rs397515358, rs137852998, rs1183237509, rs2509710080, rs2509737683, rs2509692411, rs2509774238, rs2509734575, rs1261918364, rs752924362, rs878855078, rs2509752841, rs2509693120, rs2509682200, rs2509692803, rs770946088, rs2509692646, rs2509693023, rs760845605, rs2509773951, rs1194460219, rs2509762865, rs758109864, rs2051791551, rs537816710, rs2509773849, rs2509766795, rs2509752180, rs2509766818, rs2509774436, rs2509773839, rs1242821238, rs2053427700, rs773436223, rs1060502202, rs200708870, rs141581673, rs1555614910, rs756868374, rs897911822, rs780116486, rs1240172375, rs1448501611, rs1598330492, rs1598342751, rs1598278059, rs1598348312, rs772133192, rs2051792816, rs2053367000, rs1567876609, rs2053693881, rs1177965342, rs2053566684	RCV001377385 RCV001387980 RCV001384248 RCV001382308 RCV001389419 RCV001390892 RCV002539154 RCV002037644 RCV002043982 RCV001949220 RCV001891115 RCV002013322 RCV002048662 RCV001960164 RCV001896711 RCV001953410 RCV001951047 RCV001946835 RCV002029263 RCV001983404 RCV001984747 RCV002355874 RCV002442006 RCV003058748 RCV003083103 RCV002589246 RCV001383568 RCV001385859 RCV000810716 RCV002690842 RCV002819899 RCV002876644 RCV002899114 RCV002895655 RCV002937543 RCV003054727 RCV000220262 RCV000234217 RCV003536313 RCV003536510 RCV003537695 RCV003536496 RCV003536531 RCV003535414 RCV003535508 RCV003536874 RCV003537013 RCV003648221 RCV003647505 RCV003649707 RCV003651133 RCV003651187 RCV003651297 RCV003652305 RCV003653704 RCV003652712 RCV003653883 RCV003653990 RCV003654169 RCV003650044 RCV003826648 RCV003835033 RCV000474701 RCV000471217 RCV000456361 RCV000527031 RCV000550209 RCV000560492 RCV000629457 RCV000629414 RCV000687614 RCV000686069 RCV001869133 RCV000818675 RCV000800651 RCV000806403 RCV000826102 RCV001056487 RCV001056656 RCV001057264 RCV001067024 RCV001223601 RCV001202302 RCV001244997	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Primary ciliary dyskinesia 9	Likely pathogenic; Pathogenic	rs769251936, rs545536618, rs755060592, rs745755917, rs2143904159, rs397515565, rs397515358, rs137852998, rs1261918364, rs752924362, rs2509774595, rs2509681813, rs766662586, rs1442078154, rs2509692646, rs537816710, rs200708870, rs758109864, rs756868374, rs780116486, rs1240172375, rs1598293348, rs772133192, rs1567876609	RCV005023142 RCV005014546 RCV004813185 RCV005014695 RCV002250936 RCV000005241 RCV000005242 RCV000005243 RCV005019576 RCV000410372 RCV003144790 RCV003227564 RCV003324233 RCV005636922 RCV005014788 RCV005030186 RCV004698835 RCV005018900 RCV002490939 RCV002477376 RCV005027845 RCV000991402 RCV005029629 RCV005021412	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Respiratory ciliopathies including non-CF bronchiectasis	Likely pathogenic; Pathogenic	rs758109864	RCV004584143	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CILIARY DYSKINESIA, PRIMARY, 9	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CILIARY MOTILITY DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL ATRESIA OF NASOPHARYNX	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Asthenozoospermia	Asthenozoospermia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	HPO_DG			★☆☆☆☆ Found in Text Mining only
B-Cell Lymphomas	B-Cell Lymphoma	BEFREE	30387321		★☆☆☆☆ Found in Text Mining only
Bronchiectasis	Bronchiectasis	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Bronchiectasis	Bronchiectasis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Bronchitis, Chronic	Gastric Cancer	HPO_DG			★☆☆☆☆ Found in Text Mining only
Chronic otitis media	Otitis media	HPO_DG			★☆☆☆☆ Found in Text Mining only
Chronic rhinitis	Rhinitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Chronic sinusitis	Sinusitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ciliary Dyskinesia, Primary, 1, With Or Without Situs Inversus	Ciliary Dyskinesia	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
CILIARY DYSKINESIA, PRIMARY, 9	Ciliary dyskinesia	GENOMICS_ENGLAND_DG	18950741		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CILIARY DYSKINESIA, PRIMARY, 9	Ciliary dyskinesia	CLINVAR_DG	23261302, 23891469, 25802884		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CILIARY DYSKINESIA, PRIMARY, 9	Ciliary dyskinesia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ciliary Motility Disorders	Ciliary dyskinesia	CLINVAR_DG	18950741, 23261302, 23891469, 25802884		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ciliary Motility Disorders	Ciliary dyskinesia	Pubtator	18950741, 24203976, 25186273, 33167880	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ciliary Motility Disorders	Ciliary dyskinesia	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Conductive hearing loss	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital absence of spleen	Asplenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital pectus excavatum	Congenital Pectus Excavatum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Corneal dystrophy	Corneal Dystrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Disseminated Intravascular Coagulation	Disseminated Intravascular Coagulation	BEFREE	28679481		★☆☆☆☆ Found in Text Mining only
Hydrocephalus	Hydrocephalus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hydrocephalus Normal Pressure	Normal pressure hydrocephalus	Pubtator	33167880	Associate	★☆☆☆☆ Found in Text Mining only
Hypoalphalipoproteinemias	Hypoalphalipoproteinemia	Pubtator	32541515	Associate	★☆☆☆☆ Found in Text Mining only
Kartagener Syndrome	Kartagener Syndrome	BEFREE	11153919, 18950741		★☆☆☆☆ Found in Text Mining only
Kartagener Syndrome	Kartagener Syndrome	LHGDN	18950741		★☆☆☆☆ Found in Text Mining only
Lung diseases	Lung Diseases	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Lung Diseases, Obstructive	Lung Diseases	HPO_DG			★☆☆☆☆ Found in Text Mining only
Nasal Polyps	Nasal polyposis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Nasopharyngeal Carcinoma	Nasopharyngeal carcinoma	Pubtator	30935420, 32541515	Associate	★☆☆☆☆ Found in Text Mining only
Otitis Media with Effusion	Otitis media	HPO_DG			★☆☆☆☆ Found in Text Mining only
Primary Ciliary Dyskinesia	Ciliary dyskinesia	BEFREE	11153919, 18950741, 23261302, 24203976		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Primary ciliary dyskinesia	Ciliary dyskinesia	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Primary Ciliary Dyskinesia	Ciliary dyskinesia	GENOMICS_ENGLAND_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Recurrent otitis media	Otitis media	HPO_DG			★☆☆☆☆ Found in Text Mining only
Recurrent sinusitis	Sinusitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Rhinitis	Rhinitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Situs inversus totalis	Situs Inversus	HPO_DG			★☆☆☆☆ Found in Text Mining only