DNAH9

Summary

DNAH9 (dynein axonemal heavy chain 9, HGNC:2953) is a protein-coding gene on chromosome 17p12, encoding Dynein axonemal heavy chain 9 (Q9NYC9). Force generating protein required for cilia beating in respiratory epithelia.

This gene encodes the heavy chain subunit of axonemal dynein, a large multi-subunit molecular motor. Axonemal dynein attaches to microtubules and hydrolyzes ATP to mediate the movement of cilia and flagella. The gene expresses at least two transcript variants; additional variants have been described, but their full length nature has not been determined.

Source: NCBI Gene 1770 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliary dyskinesia, primary, 40 (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 2,561 total — 94 pathogenic, 64 likely-pathogenic
• Phenotypes (HPO): 65
• MANE Select transcript: NM_001372

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2953
Approved symbol	DNAH9
Name	dynein axonemal heavy chain 9
Location	17p12
Locus type	gene with protein product
Status	Approved
Aliases	Dnahc9, KIAA0357, HL20, HL-20, DNAL1, DYH9
Ensembl gene	ENSG00000007174
Ensembl biotype	protein_coding
OMIM	603330
Entrez	1770

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 7 protein_coding, 6 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000262442, ENST00000396001, ENST00000454412, ENST00000578834, ENST00000579406, ENST00000579602, ENST00000579703, ENST00000579813, ENST00000579828, ENST00000580255, ENST00000581682, ENST00000583192, ENST00000584663, ENST00000585197, ENST00000608377

RefSeq mRNA: 2 — MANE Select: NM_001372 NM_001372, NM_004662

CCDS: CCDS11160, CCDS11161

Canonical transcript exons

ENST00000262442 — 69 exons

Exon	Start	End
ENSE00001595011	11752833	11752960
ENSE00001597644	11679757	11679979
ENSE00001597711	11822801	11823034
ENSE00001598212	11834638	11834898
ENSE00001613096	11644631	11644699
ENSE00001613245	11699731	11699883
ENSE00001618406	11768453	11768626
ENSE00001618552	11769122	11769329
ENSE00001620167	11694321	11694447
ENSE00001623797	11701122	11701247
ENSE00001623872	11640270	11640384
ENSE00001624687	11881209	11881413
ENSE00001630555	11756568	11756676
ENSE00001633448	11689566	11690436
ENSE00001645553	11704203	11704442
ENSE00001649751	11821920	11822062
ENSE00001653749	11738880	11739037
ENSE00001657977	11807732	11807894
ENSE00001671632	11793503	11793664
ENSE00001676505	11763440	11763614
ENSE00001679330	11651069	11651324
ENSE00001694939	11822438	11822599
ENSE00001695217	11680723	11680889
ENSE00001701865	11652761	11653002
ENSE00001709160	11747556	11747766
ENSE00001716540	11810246	11810369
ENSE00001727926	11669064	11669260
ENSE00001729757	11742175	11742313
ENSE00001729855	11664833	11664968
ENSE00001736393	11757545	11757692
ENSE00001740441	11797597	11797793
ENSE00001741827	11784300	11784539
ENSE00001763956	11869134	11869253
ENSE00001771381	11693868	11693998
ENSE00001778974	11744797	11745084
ENSE00001789228	11636634	11636784
ENSE00001793868	11871598	11871786
ENSE00001796724	11632587	11632703
ENSE00001798120	11781009	11781174
ENSE00001798455	11783646	11783748
ENSE00001801558	11669370	11669794
ENSE00001802718	11705025	11705185
ENSE00001805043	11647072	11647198
ENSE00001849329	11969300	11969748
ENSE00002382704	11727818	11727922
ENSE00002420293	11719334	11719490
ENSE00002725911	11598470	11598915
ENSE00003494599	11608129	11608325
ENSE00003536319	11617411	11617622
ENSE00003542814	11883586	11883750
ENSE00003543798	11874949	11875184
ENSE00003546410	11629417	11629584
ENSE00003561306	11886825	11886965
ENSE00003563660	11854003	11854428
ENSE00003607107	11619548	11619781
ENSE00003652131	11610396	11610554
ENSE00003663740	11611650	11611780
ENSE00003702770	11923814	11923941
ENSE00003702847	11902719	11902912
ENSE00003703373	11891777	11891947
ENSE00003704013	11894374	11894496
ENSE00003704281	11937352	11937522
ENSE00003705220	11933880	11934071
ENSE00003705265	11929866	11930093
ENSE00003705787	11961867	11962256
ENSE00003705968	11905661	11905809
ENSE00003708521	11932014	11932205
ENSE00003708996	11942303	11942485
ENSE00003785709	11880078	11880200

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 98.83.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6700 / max 50.3412, expressed in 202 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159604	0.4145	165
159606	0.1524	60
159605	0.1032	57

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	98.83	gold quality
bronchial epithelial cell	CL:0002328	96.22	gold quality
epithelium of bronchus	UBERON:0002031	95.53	gold quality
bronchus	UBERON:0002185	94.52	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.41	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.03	gold quality
epithelium of nasopharynx	UBERON:0001951	81.72	gold quality
nasopharynx	UBERON:0001728	81.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.44	gold quality
sperm	CL:0000019	80.26	silver quality
nasal cavity mucosa	UBERON:0001826	79.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.69	gold quality
male germ cell	CL:0000015	78.93	silver quality
fallopian tube	UBERON:0003889	78.85	gold quality
caudate nucleus	UBERON:0001873	78.64	gold quality
secondary oocyte	CL:0000655	78.45	gold quality
hypothalamus	UBERON:0001898	78.17	gold quality
spinal cord	UBERON:0002240	78.03	gold quality
nucleus accumbens	UBERON:0001882	77.87	gold quality
right testis	UBERON:0004534	77.83	gold quality
prefrontal cortex	UBERON:0000451	77.79	gold quality
amygdala	UBERON:0001876	77.46	gold quality
left testis	UBERON:0004533	77.45	gold quality
nasal cavity epithelium	UBERON:0005384	77.15	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.97	gold quality
cranial nerve II	UBERON:0000941	76.88	gold quality
choroid plexus epithelium	UBERON:0003911	76.37	silver quality
Brodmann (1909) area 9	UBERON:0013540	76.37	gold quality
Ammon’s horn	UBERON:0001954	76.09	gold quality
testis	UBERON:0000473	75.78	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	2917.44
E-MTAB-10287	yes	25.20
E-MTAB-9388	yes	7.06
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR2

miRNA regulators (miRDB)

8 targeting DNAH9, 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-1250-3P	99.96	70.04	4038
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-6847-3P	96.50	67.30	582
HSA-MIR-642B-5P	96.37	67.26	745

Literature-anchored findings (GeneRIF, showing 8)

• DNAH9 gene has a role in early smoke exposure in bronchial hyperresponsiveness (PMID:26797031)
• DNAH9 is widely expressed in the airways. (PMID:30471717)
• The beta-HC paralogs DNAH9 and DNAH11 achieved specific functional roles for the distinct axonemal compartments during evolution. (PMID:30471718)
• Novel variants in DNAH9 lead to nonsyndromic severe asthenozoospermia. (PMID:33610189)
• Whole-exome sequencing reveals a combination of extremely rare single-nucleotide polymorphism of DNAH9 and RSPH1 genes in a Japanese fetus with situs viscerum inversus. (PMID:34008076)
• Biallelic DNAH9 mutations are identified in Chinese patients with defective left-right patterning and cilia-related complex congenital heart disease. (PMID:35050399)
• Clustering of Genetic Anomalies of Cilia Outer Dynein Arm and Central Apparatus in Patients with Transposition of the Great Arteries. (PMID:36140829)
• Meta-analysis of Transcriptomic Data from Lung Autopsy and Cellular Models of SARS-CoV-2 Infection. (PMID:37486510)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnah9	ENSDARG00000103383
mus_musculus	Dnah9	ENSMUSG00000056752
rattus_norvegicus	Dnah9	ENSRNOG00000004171
drosophila_melanogaster	Dhc93AB	FBGN0013812
drosophila_melanogaster	CG3339	FBGN0039510
drosophila_melanogaster	kl-5	FBGN0267433

Paralogs (15): DNAH5 (ENSG00000039139), DNAH11 (ENSG00000105877), DNAH1 (ENSG00000114841), DNAH6 (ENSG00000115423), DNAH7 (ENSG00000118997), DNAH8 (ENSG00000124721), DNAH3 (ENSG00000158486), DNAH12 (ENSG00000174844), DNHD1 (ENSG00000179532), DNAH2 (ENSG00000183914), DNAH14 (ENSG00000185842), DYNC2H1 (ENSG00000187240), DNAH17 (ENSG00000187775), DYNC1H1 (ENSG00000197102), DNAH10 (ENSG00000197653)

Protein

Protein identifiers

Dynein axonemal heavy chain 9 — Q9NYC9 (reviewed: Q9NYC9)

Alternative names: Axonemal beta dynein heavy chain 9, Ciliary dynein heavy chain 9

All UniProt accessions (6): Q9NYC9, E7EP17, J3QLM9, J3QQK8, K7EMX3, K7EP21

UniProt curated annotations — full annotation on UniProt →

Function. Force generating protein required for cilia beating in respiratory epithelia. Produces force towards the minus ends of microtubules. Key component of dynein, a family of motor proteins essential for movement along microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Required for structural and functional integrity of cilia.

Subunit / interactions. 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 ODAD1.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme. Cell projection. Cilium. Flagellum.

Tissue specificity. Expressed in upper and lower respiratory airway epithelia (at protein level). Not detected in spermatozoa (at protein level).

Disease relevance. Ciliary dyskinesia, primary, 40 (CILD40) [MIM:618300] A form of primary ciliary dyskinesia, 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. Some patients exhibit randomization of left-right body asymmetry and situs inversus. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD40 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Dynein heavy chains probably consist of an N-terminal stem (which binds cargo and interacts with other dynein components), and the head or motor domain. The motor contains six tandemly-linked AAA domains in the head, which form a ring. A stalk-like structure (formed by two of the coiled coil domains) protrudes between AAA 4 and AAA 5 and terminates in a microtubule-binding site. A seventh domain may also contribute to this ring; it is not clear whether the N-terminus or the C-terminus forms this extra domain. There are four well-conserved and two non-conserved ATPase sites, one per AAA domain. Probably only one of these (within AAA 1) actually hydrolyzes ATP, the others may serve a regulatory function.

Similarity. Belongs to the dynein heavy chain family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NYC9-1	1	yes
Q9NYC9-2	2
Q9NYC9-3	3

RefSeq proteins (2): NP_001363, NP_004653 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR004273	Dhc_D6_P-loop	Domain
IPR013594	Dynein_heavy_tail	Domain
IPR013602	Dhc_linker	Domain
IPR024317	Dhc_D4	Domain
IPR024743	Dynein_HC_stalk	Domain
IPR026983	DHC	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR035699	Dhc_AAA	Domain
IPR035706	AAA_9	Domain
IPR041228	Dhc_C	Domain
IPR041466	Dhc_AAA5_ext	Domain
IPR041589	DNAH3_AAA_lid_1	Domain
IPR041658	AAA_lid_11	Domain
IPR042219	AAA_lid_11_sf	Homologous_superfamily
IPR042222	Dynein_2_N	Homologous_superfamily
IPR042228	Dynein_linker_3	Homologous_superfamily
IPR043157	Dynein_AAA1S	Homologous_superfamily
IPR043160	Dynein_C_barrel	Homologous_superfamily

Pfam: PF03028, PF08385, PF08393, PF12774, PF12775, PF12777, PF12780, PF12781, PF17852, PF17857, PF18198, PF18199

UniProt features (53 total): sequence variant 27, region of interest 8, coiled-coil region 8, binding site 4, sequence conflict 3, splice variant 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

No AlphaFold model available for Q9NYC9 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Ligand- & substrate-binding residues (4): 1870–1877; 2151–2158; 2478–2485; 2825–2832

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 352 (showing top): chr17p12, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, TGCGCANK_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_RESPIRATORY_SYSTEM_PROCESS, GOCC_MICROTUBULE_ORGANIZING_CENTER, EFC_Q6, GOBP_AXONEMAL_DYNEIN_COMPLEX_ASSEMBLY, chr14q24, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, KEGG_HUNTINGTONS_DISEASE

GO Biological Process (7): cilium movement (GO:0003341), cell projection organization (GO:0030030), establishment of localization in cell (GO:0051649), cilium movement involved in cell motility (GO:0060294), cerebrospinal fluid circulation (GO:0090660), mucociliary clearance (GO:0120197), microtubule-based movement (GO:0007018)

GO Molecular Function (7): ATP binding (GO:0005524), minus-end-directed microtubule motor activity (GO:0008569), dynein intermediate chain binding (GO:0045505), dynein light intermediate chain binding (GO:0051959), nucleotide binding (GO:0000166), protein binding (GO:0005515), ATP hydrolysis activity (GO:0016887)

GO Cellular Component (13): extracellular region (GO:0005576), microtubule (GO:0005874), axoneme (GO:0005930), dynein complex (GO:0030286), motile cilium (GO:0031514), outer dynein arm (GO:0036157), glial cell projection (GO:0097386), 9+2 motile cilium (GO:0097729), distal portion of axoneme (GO:0120135), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
epithelial cilium movement involved in extracellular fluid movement	2
protein binding	2
plasma membrane bounded cell projection	2
microtubule-based movement	1
cellular component organization	1
establishment of localization	1
cellular localization	1
cilium movement	1
cell motility	1
cilium-dependent cell motility	1
nervous system process	1
respiratory system process	1
microtubule-based process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
microtubule motor activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
microtubule associated complex	1
catalytic complex	1
cilium	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
axoneme	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1814 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAH9	DNAI2	Q9GZS0	804
DNAH9	DNAI1	Q9UI46	780
DNAH9	DNAAF1	Q8NEP3	714
DNAH9	DNALI1	O14645	701
DNAH9	RSPH4A	Q5TD94	620
DNAH9	DNAAF19	Q8IW40	617
DNAH9	DRC4	O95995	603
DNAH9	RSPH1	Q8WYR4	602
DNAH9	DNAAF3	Q8N9W5	600
DNAH9	CCDC39	Q9UFE4	596
DNAH9	DYNC1I2	Q13409	595
DNAH9	CCDC40	Q4G0X9	594
DNAH9	SPAG6	O75602	591
DNAH9	DNAH12	Q6ZR08	590
DNAH9	ODAD1	Q96M63	586

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ODAD1	DNAH9	psi-mi:“MI:0915”(physical association)	0.510
BCL6	CACNA1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): FAM103A1 (Co-fractionation), DNAH9 (Biochemical Activity), DNAH9 (Affinity Capture-MS), DNAH9 (Proximity Label-MS), DNAH9 (Affinity Capture-MS), DNAH9 (Affinity Capture-MS), DNAH9 (Affinity Capture-MS), DNAH9 (Proximity Label-MS), DNAH9 (Affinity Capture-MS), DNAH9 (Affinity Capture-MS), DNAH9 (Cross-Linking-MS (XL-MS)), NEFM (Cross-Linking-MS (XL-MS)), HIST1H3A (Cross-Linking-MS (XL-MS)), IWS1 (Cross-Linking-MS (XL-MS)), CANX (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: F1SC07, M0R8U1, O44218, O44518, P0C6F1, P23098, P36022, P37276, P38650, P39057, P45443, P45444, P78716, Q14204, Q18286, Q19020, Q19542, Q22706, Q27802, Q299G2, Q39565, Q39575, Q3V0Q1, Q54R74, Q61JT8, Q63170, Q69Z23, Q6ZR08, Q8BW94, Q8IVF4, Q8TD57, Q8TE73, Q8VHE6, Q8WXX0, Q91XQ0, Q923J6, Q96DT5, Q96JB1, Q9C1M7, Q9JHU4

Diamond homologs: E9Q8T7, F1SC07, M0R8U1, P0C6F1, P23098, P39057, Q39565, Q39575, Q39610, Q3V0Q1, Q63164, Q63170, Q69Z23, Q6ZR08, Q8BW94, Q8IVF4, Q8TD57, Q8TE73, Q8VHE6, Q8WXX0, Q91XQ0, Q923J6, Q96DT5, Q96JB1, Q9C0G6, Q9MBF8, Q9NYC9, Q9P225, Q9P2D7, Q9SMH3, Q9UFH2, P84753, O75369, P80197, P87061, Q2R2W1, Q5Z8K3, Q67UX0, Q7M3S9, Q80X90

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

2561 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	94
Likely pathogenic	64
Uncertain significance	1157
Likely benign	904
Benign	236

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1065458	NM_001372.4(DNAH9):c.4234C>T (p.Gln1412Ter)	Pathogenic
1065498	NM_001372.4(DNAH9):c.2984del (p.Arg995fs)	Pathogenic
1322757	NM_001372.4(DNAH9):c.760_761del (p.Phe254fs)	Pathogenic
1358881	NM_001372.4(DNAH9):c.4719T>G (p.Tyr1573Ter)	Pathogenic
1363635	NM_001372.4(DNAH9):c.4193del (p.Thr1398fs)	Pathogenic
1396137	NM_001372.4(DNAH9):c.8992C>T (p.Gln2998Ter)	Pathogenic
1400712	NM_001372.4(DNAH9):c.3051T>A (p.Tyr1017Ter)	Pathogenic
1430657	NM_001372.4(DNAH9):c.10440T>A (p.Tyr3480Ter)	Pathogenic
1442938	NM_001372.4(DNAH9):c.6213_6228del (p.Met2071fs)	Pathogenic
1451912	NM_001372.4(DNAH9):c.4432C>T (p.Gln1478Ter)	Pathogenic
1453048	NM_001372.4(DNAH9):c.10242+1G>C	Pathogenic
1456273	NM_001372.4(DNAH9):c.2497del (p.Arg833fs)	Pathogenic
1458739	NM_001372.4(DNAH9):c.310dup (p.Leu104fs)	Pathogenic
1710144	NM_001372.4(DNAH9):c.5266C>T (p.Gln1756Ter)	Pathogenic
1902923	NM_001372.4(DNAH9):c.2151_2152del (p.Met718fs)	Pathogenic
1926525	NM_001372.4(DNAH9):c.7150G>A (p.Gly2384Arg)	Pathogenic
1933496	NM_001372.4(DNAH9):c.1333_1334inv (p.Gln445Ter)	Pathogenic
1963108	NM_001372.4(DNAH9):c.7950dup (p.Leu2651fs)	Pathogenic
1971238	NM_001372.4(DNAH9):c.7888_7903del (p.Ile2629_Ile2630insTer)	Pathogenic
1979298	NM_001372.4(DNAH9):c.12844-1G>C	Pathogenic
1984400	NM_001372.4(DNAH9):c.11299C>T (p.Arg3767Ter)	Pathogenic
1992905	NM_001372.4(DNAH9):c.19_41delinsAACGCGGATGGGGAACCCGGCGCCGAC (p.Arg7fs)	Pathogenic
2029085	NM_001372.4(DNAH9):c.13002G>A (p.Trp4334Ter)	Pathogenic
2034074	NM_001372.4(DNAH9):c.12730A>T (p.Lys4244Ter)	Pathogenic
2034521	NM_001372.4(DNAH9):c.9862dup (p.Ala3288fs)	Pathogenic
2046953	NM_001372.4(DNAH9):c.5505G>C (p.Glu1835Asp)	Pathogenic
2129786	NM_001372.4(DNAH9):c.1038G>A (p.Trp346Ter)	Pathogenic
2133250	NM_001372.4(DNAH9):c.10600C>T (p.Arg3534Ter)	Pathogenic
2424145	NC_000017.10:g.(?11556078)(11556319_?)del	Pathogenic
2424146	NC_000017.10:g.(?11622631)(11622827_?)del	Pathogenic

SpliceAI

10663 predictions. Top by Δscore:

Variant	Effect	Δscore
17:11598913:G:GT	donor_gain	1.0000
17:11608322:CAGT:C	donor_gain	1.0000
17:11608324:GT:G	donor_gain	1.0000
17:11608326:G:GG	donor_gain	1.0000
17:11610391:CACA:C	acceptor_loss	1.0000
17:11610393:C:G	acceptor_gain	1.0000
17:11610394:A:AG	acceptor_gain	1.0000
17:11610394:A:AT	acceptor_loss	1.0000
17:11610394:AGCTT:A	acceptor_gain	1.0000
17:11610395:G:GG	acceptor_gain	1.0000
17:11610395:GCT:G	acceptor_gain	1.0000
17:11610395:GCTT:G	acceptor_gain	1.0000
17:11610395:GCTTG:G	acceptor_gain	1.0000
17:11610510:G:T	donor_gain	1.0000
17:11617618:AGCAG:A	donor_loss	1.0000
17:11617620:CAG:C	donor_loss	1.0000
17:11617621:AGG:A	donor_loss	1.0000
17:11617622:GGTG:G	donor_loss	1.0000
17:11617623:GTGGG:G	donor_loss	1.0000
17:11617624:T:A	donor_loss	1.0000
17:11629413:ATAG:A	acceptor_gain	1.0000
17:11629414:TAGGG:T	acceptor_loss	1.0000
17:11629415:A:AC	acceptor_loss	1.0000
17:11629415:A:AG	acceptor_gain	1.0000
17:11629415:AG:A	acceptor_gain	1.0000
17:11629416:G:GG	acceptor_gain	1.0000
17:11629416:GG:G	acceptor_gain	1.0000
17:11629416:GGGT:G	acceptor_gain	1.0000
17:11629416:GGGTC:G	acceptor_gain	1.0000
17:11629528:GAGAT:G	donor_gain	1.0000

AlphaMissense

29705 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:11752922:T:A	W2234R	1.000
17:11752922:T:C	W2234R	1.000
17:11752939:T:A	N2239K	1.000
17:11752939:T:G	N2239K	1.000
17:11752949:G:C	D2243H	1.000
17:11719404:G:C	G1875R	0.999
17:11719405:G:A	G1875D	0.999
17:11727860:T:A	W1918R	0.999
17:11727860:T:C	W1918R	0.999
17:11727872:G:C	D1922H	0.999
17:11727873:A:C	D1922A	0.999
17:11727873:A:G	D1922G	0.999
17:11727873:A:T	D1922V	0.999
17:11727875:G:A	E1923K	0.999
17:11727876:A:C	E1923A	0.999
17:11727876:A:G	E1923G	0.999
17:11727876:A:T	E1923V	0.999
17:11727877:G:C	E1923D	0.999
17:11727877:G:T	E1923D	0.999
17:11738984:C:A	N1973K	0.999
17:11738984:C:G	N1973K	0.999
17:11752889:T:A	W2223R	0.999
17:11752889:T:C	W2223R	0.999
17:11752950:A:T	D2243V	0.999
17:11752951:T:A	D2243E	0.999
17:11752951:T:G	D2243E	0.999
17:11756671:G:C	R2281T	0.999
17:11756671:G:T	R2281I	0.999
17:11756672:A:C	R2281S	0.999
17:11756672:A:T	R2281S	0.999

dbSNP variants (sampled 300 via entrez): RS1000005277 (17:11939805 T>C), RS1000005952 (17:11664258 G>A), RS1000038061 (17:11909454 G>A), RS1000038185 (17:11746280 T>A), RS1000041864 (17:11779994 T>C), RS1000041873 (17:11664603 T>C), RS1000049093 (17:11898266 C>A,T), RS1000080003 (17:11766754 G>A), RS1000081116 (17:11706445 T>A), RS1000093301 (17:11746409 A>G), RS1000094566 (17:11601622 A>G), RS1000098791 (17:11828127 C>A,G), RS1000110517 (17:11868882 G>C), RS1000112041 (17:11706376 G>A), RS1000135437 (17:11600605 A>C,G)

Disease associations

OMIM: gene MIM:603330 | disease phenotypes: MIM:618300, MIM:236750, MIM:244400, MIM:181500, MIM:620356, MIM:614896, MIM:608644, MIM:610805

GenCC curated gene-disease

Disease	Classification	Inheritance
ciliary dyskinesia, primary, 40	Definitive	Autosomal recessive
situs inversus	Supportive	Autosomal dominant
primary ciliary dyskinesia	Supportive	Autosomal dominant
schizophrenia	Limited	Autosomal dominant

Mondo (13): ciliary dyskinesia, primary, 40 (MONDO:0032664), non-immune hydrops fetalis (MONDO:0009369), primary ciliary dyskinesia (MONDO:0016575), hydrocephalus (MONDO:0001150), congenital heart disease (MONDO:0005453), prostate cancer (MONDO:0008315), schizophrenia (MONDO:0005090), ciliary dyskinesia, primary, 50 (MONDO:0957252), sinoatrial node dysfunction and deafness (MONDO:0013960), primary ciliary dyskinesia 3 (MONDO:0012085), male infertility (MONDO:0005372), congenital anomaly of kidney and urinary tract (MONDO:0019719), situs inversus (MONDO:0010029)

Orphanet (6): Non-immune hydrops fetalis (Orphanet:363999), Primary ciliary dyskinesia (Orphanet:244), Familial prostate cancer (Orphanet:1331), Sinoatrial node dysfunction and deafness (Orphanet:324321), Renal or urinary tract malformation (Orphanet:93545), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

65 total (30 of 65 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000027	Azoospermia
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:0001643	Patent ductus arteriosus
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:0002257	Chronic rhinitis
HP:0002566	Intestinal malrotation
HP:0002643	Neonatal respiratory distress
HP:0002878	Respiratory failure
HP:0003251	Male infertility
HP:0003577	Congenital onset

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001712_58	Myopia (pathological)	3.000000e-06
GCST002441_3	Immune response to measles-mumps-rubella vaccine	1.000000e-07
GCST003455_1	Spherical equivalent (joint analysis main effects and education interaction)	3.000000e-12
GCST003455_27	Spherical equivalent (joint analysis main effects and education interaction)	3.000000e-10
GCST006222_2	Cerebellum growth	8.000000e-06
GCST007622_5	Impulsivity	1.000000e-06
GCST010002_120	Refractive error	4.000000e-84
GCST012490_56	Femur bone mineral density x serum urate levels interaction	3.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004207	pathological myopia
EFO:0004645	response to vaccine
EFO:0004784	self reported educational attainment
EFO:0006946	behavioural disinhibition measurement
EFO:0004531	urate measurement

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D002925	Ciliary Motility Disorders	C08.200; C09.150; C16.131.077.245.500; C16.320.184.500
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D006849	Hydrocephalus	C10.228.140.602
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
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D012857	Situs Inversus	C16.131.810
C566906	Cakut (supp.)
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

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	increases methylation, increases mutagenesis, affects methylation, decreases methylation	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	increases expression	2
arsenite	increases methylation	1
benzo(e)pyrene	decreases methylation	1
nickel sulfate	decreases expression	1
coumarin	increases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
Lead	affects methylation	1
Methapyrilene	decreases methylation	1
Smoke	increases abundance, increases expression	1
Testosterone	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety