DNAH5

Summary

DNAH5 (dynein axonemal heavy chain 5, HGNC:2950) is a protein-coding gene on chromosome 5p15.2, encoding Dynein axonemal heavy chain 5 (Q8TE73). Force generating protein of respiratory cilia.

This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects.

Source: NCBI Gene 1767 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary ciliary dyskinesia 3 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 24
• Clinical variants (ClinVar): 6,610 total — 520 pathogenic, 422 likely-pathogenic
• Phenotypes (HPO): 54
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001369

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2950
Approved symbol	DNAH5
Name	dynein axonemal heavy chain 5
Location	5p15.2
Locus type	gene with protein product
Status	Approved
Aliases	Dnahc5, HL1, PCD, CILD3, KTGNR
Ensembl gene	ENSG00000039139
Ensembl biotype	protein_coding
OMIM	603335
Entrez	1767

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 8 retained_intron, 4 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000265104, ENST00000504001, ENST00000508040, ENST00000512443, ENST00000680213, ENST00000681290, ENST00000682376, ENST00000682586, ENST00000683011, ENST00000683090, ENST00000683611, ENST00000683967, ENST00000684013, ENST00000684099

RefSeq mRNA: 1 — MANE Select: NM_001369 NM_001369

CCDS: CCDS3882

Canonical transcript exons

ENST00000265104 — 79 exons

Exon	Start	End
ENSE00000726008	13708123	13708335
ENSE00000726013	13701284	13701436
ENSE00000846095	13700640	13700871
ENSE00000908779	13714405	13714620
ENSE00000908780	13716487	13716690
ENSE00000908781	13717315	13717520
ENSE00000908782	13718882	13719101
ENSE00000908784	13727507	13727656
ENSE00000908785	13729439	13729560
ENSE00000908786	13735131	13735321
ENSE00000908787	13735818	13735932
ENSE00000908788	13737252	13737495
ENSE00000908789	13751078	13751260
ENSE00000908790	13752134	13752289
ENSE00000908791	13753233	13753549
ENSE00000970968	13871564	13871765
ENSE00000970970	13867774	13867992
ENSE00000970971	13866220	13866282
ENSE00000970972	13865668	13865906
ENSE00000970974	13862548	13862747
ENSE00000970976	13850652	13850815
ENSE00000970978	13841692	13841904
ENSE00000970979	13840906	13841130
ENSE00001014238	13894650	13894821
ENSE00001014245	13911386	13911493
ENSE00001014248	13765976	13766179
ENSE00001014255	13788716	13788914
ENSE00001014263	13900206	13900412
ENSE00001014265	13762722	13762901
ENSE00001014278	13721000	13721245
ENSE00001014282	13758846	13758983
ENSE00001014292	13885964	13886129
ENSE00001014308	13776439	13776706
ENSE00001082619	13807591	13807725
ENSE00001082629	13882728	13882815
ENSE00001133931	13777202	13777355
ENSE00001133937	13786179	13786351
ENSE00001133946	13791994	13792217
ENSE00001133969	13810059	13810260
ENSE00001134019	13839356	13839528
ENSE00001134033	13844837	13844993
ENSE00001134040	13859452	13859605
ENSE00001134047	13864397	13864637
ENSE00001134053	13870767	13871002
ENSE00001134059	13876684	13876817
ENSE00001134062	13882904	13883094
ENSE00001134067	13884989	13885228
ENSE00001134073	13890976	13891121
ENSE00001134080	13901252	13901573
ENSE00001134252	13780829	13780959
ENSE00001134281	13793515	13793728
ENSE00001134507	13902053	13902138
ENSE00001166120	13754203	13754338
ENSE00001271228	13690328	13692135
ENSE00001271250	13919176	13919352
ENSE00001299195	13823263	13823370
ENSE00001300374	13830026	13830213
ENSE00001305145	13820346	13820499
ENSE00001306632	13814605	13814846
ENSE00001317764	13824199	13824333
ENSE00001319059	13829510	13829704
ENSE00001325567	13817548	13817694
ENSE00001327140	13811647	13811823
ENSE00001380907	13944382	13944688
ENSE00001721894	13830597	13830775
ENSE00001772324	13793936	13794058
ENSE00003476939	13917143	13917256
ENSE00003481430	13920480	13920617
ENSE00003510444	13922107	13922328
ENSE00003535513	13770749	13770980
ENSE00003544543	13916348	13916455
ENSE00003548872	13809044	13809186
ENSE00003573638	13768960	13769136
ENSE00003603288	13931110	13931244
ENSE00003624637	13769501	13769615
ENSE00003648602	13928094	13928178
ENSE00003651576	13914520	13914642
ENSE00003664761	13913743	13913958
ENSE00003683418	13923280	13923440

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 99.26.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4657 / max 109.9689, expressed in 559 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60958	1.4657	559

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.26	gold quality
bronchus	UBERON:0002185	98.26	gold quality
oviduct epithelium	UBERON:0004804	98.03	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.10	gold quality
epithelium of nasopharynx	UBERON:0001951	90.86	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.97	gold quality
nasal cavity epithelium	UBERON:0005384	84.78	gold quality
right uterine tube	UBERON:0001302	83.89	gold quality
pancreatic ductal cell	CL:0002079	82.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.04	gold quality
nasal cavity mucosa	UBERON:0001826	79.51	gold quality
fallopian tube	UBERON:0003889	76.81	gold quality
epithelial cell of pancreas	CL:0000083	76.41	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.32	gold quality
islet of Langerhans	UBERON:0000006	72.14	gold quality
trachea	UBERON:0003126	71.68	gold quality
lower lobe of lung	UBERON:0008949	69.92	gold quality
caput epididymis	UBERON:0004358	69.52	gold quality
upper arm skin	UBERON:0004263	69.00	gold quality
kidney epithelium	UBERON:0004819	67.80	silver quality
buccal mucosa cell	CL:0002336	67.53	silver quality
right lung	UBERON:0002167	67.47	gold quality
calcaneal tendon	UBERON:0003701	66.70	gold quality
cortical plate	UBERON:0005343	66.04	gold quality
germinal epithelium of ovary	UBERON:0001304	65.55	gold quality
palpebral conjunctiva	UBERON:0001812	65.24	gold quality
pancreas	UBERON:0001264	65.00	gold quality
secondary oocyte	CL:0000655	64.95	gold quality
lung	UBERON:0002048	64.70	gold quality
pituitary gland	UBERON:0000007	63.60	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	62.53
E-HCAD-1	yes	26.50
E-GEOD-130148	yes	12.58
E-MTAB-9388	yes	7.45
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

64 targeting DNAH5, 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-126-5P	100.00	72.71	3180
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-377-3P	99.37	70.18	1905

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 23)

• immunofluorescence studies of respiratory epithelial cells with secondary ciliary dyskinesia identified in vitro and in vivo normal axonemal DNAH5 localization (PMID:16492982)
• DNAH5 is frequently mutated in patients with primary ciliary dyskinesia exhibiting outer dynein arm defects and mutations cluster in five exons. (PMID:16627867)
• 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)
• Although genetic alterations remain to be identified in most patients, DNAH5 is to date the main PCD gene. (PMID:19357118)
• Two “major” genes, DNAI1 and DNAH5, underlie PCD in nearly half of the patients with ODA defects (PMID:19410201)
• DNAH5 is the cause of primary ciliary dyskinesia in two siblings in a nuclear family as identified by whole genome sequencing. (PMID:20220176)
• DNAH5 (rs2277046) is associated with single nucleotide polymorphisms in Korean patients, either non-segmental or segmental type. (PMID:23678272)
• A novel mutation in DNAH5 (c. 8030G>A) is identified in a Han Chinese family with chronic rhinosinusitis and primary ciliary dyskinesia. (PMID:24150548)
• The mutation of p.Glu2610Gly in DNAH5 is novel. (PMID:24912412)
• In chronic obstructive pulmonary disease, total lung capacity was associated with a SNP in DNAH5. (PMID:25134640)
• to the best of our knowledge, the first reported case of PCD caused by the DNAH5 mutation in a Japanese patient. (PMID:27779714)
• These findings demonstrated that new DNAH5 mutations could be used for molecular diagnosis of Kartagener syndrome, providing families with genetic counseling and prenatal diagnosis. (PMID:27988889)
• Both DNAH5 and ADGRV1 contribute to ciliary function. (PMID:28927820)
• A novel mutation causing primary ciliary dyskinesia was found in Japanese patients. (PMID:28939216)
• We identified two rare nonsynonymous variants in the dynein axonemal heavy chain 5 gene (DNAH5): a previously reported variant c.7502G > C; p.(R2501P), and a novel variant c.12043 T > G; p.(Y4015D). . Individual 2 had non-syndromic SI and DD. In individual 2, one rare variant (c.9110A > G;p.(H3037R)) in the dynein axonemal heavy chain 11 gene (DNAH11), coding for another component of the outer dynein arm, was identified. (PMID:32357925)
• Genome-wide association analysis of cognitive function in Danish long-lived individuals. (PMID:33607172)
• Novel compound heterozygous mutations of DNAH5 identified in a pediatric patient with Kartagener syndrome: case report and literature review. (PMID:34391405)
• Novel homozygous mutations of DNAH5 in Kartagener syndrome. (PMID:34962988)
• Genome-wide association study in minority children with asthma implicates DNAH5 in bronchodilator responsiveness. (PMID:35869121)
• DNAH5 gene and its correlation with linc02220 expression and sperm characteristics. (PMID:35960414)
• Characteristic genetic spectrum of primary ciliary dyskinesia in Japanese patients and global ethnic heterogeneity: population-based genomic variation database analysis. (PMID:36864285)
• Identification and validation of a prognostic-related mutant gene DNAH5 for hepatocellular carcinoma. (PMID:38022557)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnah5	ENSDARG00000087373
mus_musculus	Dnah5	ENSMUSG00000022262
rattus_norvegicus	Dnah5	ENSRNOG00000048363
drosophila_melanogaster	kl-3	FBGN0267432

Paralogs (15): DNAH9 (ENSG00000007174), 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 5 — Q8TE73 (reviewed: Q8TE73)

Alternative names: Axonemal beta dynein heavy chain 5, Ciliary dynein heavy chain 5

All UniProt accessions (2): A0A7P0Z455, Q8TE73

UniProt curated annotations — full annotation on UniProt →

Function. Force generating protein of respiratory cilia. 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 the cilia of ependymal cells lining the brain ventricles.

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 DNAL1.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme.

Tissue specificity. Expressed in airway epithelial cells (at protein level). Not detected in spermatozoa (at protein level).

Disease relevance. Ciliary dyskinesia, primary, 3 (CILD3) [MIM:608644] 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.

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.

RefSeq proteins (1): NP_001360* (*=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
IPR056759	DYH2-5-8_CC	Domain

Pfam: PF03028, PF08385, PF08393, PF12774, PF12775, PF12777, PF12780, PF12781, PF17852, PF17857, PF18198, PF18199, PF25007

UniProt features (56 total): sequence variant 29, sequence conflict 9, region of interest 8, coiled-coil region 7, binding site 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 Q8TE73 — 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 (2): 1980–1987; 2262–2269

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 222 (showing top): GOBP_VENTRICULAR_SYSTEM_DEVELOPMENT, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_AXONEMAL_DYNEIN_COMPLEX_ASSEMBLY, JOHANSSON_BRAIN_CANCER_EARLY_VS_LATE_UP, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_OUTER_DYNEIN_ARM_ASSEMBLY, GOBP_ORGANELLE_ASSEMBLY, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_HEAD_DEVELOPMENT, HOOI_ST7_TARGETS_DN

GO Biological Process (11): 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), lateral ventricle development (GO:0021670), flagellated sperm motility (GO:0030317), outer dynein arm assembly (GO:0036158), establishment of localization in cell (GO:0051649), cilium assembly (GO:0060271), cilium movement involved in cell motility (GO:0060294), 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), microtubule motor activity (GO:0003777), ATP hydrolysis activity (GO:0016887)

GO Cellular Component (14): extracellular region (GO:0005576), cytoplasm (GO:0005737), microtubule (GO:0005874), axoneme (GO:0005930), motile cilium (GO:0031514), outer dynein arm (GO:0036157), glial cell projection (GO:0097386), 9+0 motile cilium (GO:0097728), 9+2 motile cilium (GO:0097729), cytoskeleton (GO:0005856), axonemal dynein complex (GO:0005858), cilium (GO:0005929), dynein complex (GO:0030286), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cilium movement	2
cilium-dependent cell motility	2
protein binding	2
ATP-dependent activity	2
plasma membrane bounded cell projection	2
motile cilium	2
inner dynein arm	2
outer dynein arm	2
axonemal doublet microtubule	2
microtubule-based 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
telencephalon development	1
ventricular system development	1
anatomical structure development	1
cilium movement involved in cell motility	1
sperm motility	1
axonemal dynein complex assembly	1
establishment of localization	1
cellular localization	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
cell motility	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

Protein interactions and networks

STRING

1784 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAH5	DNAI2	Q9GZS0	991
DNAH5	DNAI1	Q9UI46	983
DNAH5	DNALI1	O14645	975
DNAH5	DNAAF1	Q8NEP3	961
DNAH5	RSPH4A	Q5TD94	955
DNAH5	RSPH9	Q9H1X1	933
DNAH5	NME8	Q8N427	924
DNAH5	DNAAF2	Q9NVR5	916
DNAH5	DNAL1	Q4LDG9	870
DNAH5	DNAH12	Q6ZR08	860
DNAH5	ODAD1	Q96M63	854
DNAH5	ODAD2	Q5T2S8	836
DNAH5	M9MMK7	M9MMK7	834
DNAH5	CCDC39	Q9UFE4	818
DNAH5	CCDC40	Q4G0X9	816

IntAct

16 interactions, top by confidence:

A	B	Type	Score
PATL2	DNAH5	psi-mi:“MI:0915”(physical association)	0.400
RRBP1	DNAH5	psi-mi:“MI:0915”(physical association)	0.400
BICD2	DNAH5	psi-mi:“MI:0915”(physical association)	0.400
DNAH5	H2AC4	psi-mi:“MI:0915”(physical association)	0.400
DNAH5	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
DNAH5	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
H3-4	DNAH5	psi-mi:“MI:0915”(physical association)	0.400
DNAH5	PLEC	psi-mi:“MI:0915”(physical association)	0.400
DNAH5	UBA52	psi-mi:“MI:0915”(physical association)	0.400
DNAH5	H2AC12	psi-mi:“MI:0915”(physical association)	0.400
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
TAGLN	LOC392647	psi-mi:“MI:0914”(association)	0.350
DNAH5	EIF4A2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (34): DNAH5 (Protein-RNA), DNAH5 (Affinity Capture-MS), DNAH5 (Affinity Capture-MS), DNAH5 (Affinity Capture-MS), DNAH5 (Proximity Label-MS), HIST1H2AH (Proximity Label-MS), DNAH5 (Proximity Label-MS), DNAH5 (Proximity Label-MS), DNAH5 (Proximity Label-MS), DNAH5 (Proximity Label-MS), DNAH5 (Proximity Label-MS), DNAH5 (Proximity Label-MS), HIST1H2BH (Proximity Label-MS), RRBP1 (Proximity Label-MS), DNAH5 (Affinity Capture-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

1 interactions.

A	Effect	B	Mechanism
CFAP53	“up-regulates activity”	DNAH5	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 16 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ub-specific processing proteases	5	24.1×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

6610 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	520
Likely pathogenic	422
Uncertain significance	1466
Likely benign	3004
Benign	352

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012301	NM_001369.3(DNAH5):c.9033del (p.Phe3011fs)	Pathogenic
1012302	NM_001369.3(DNAH5):c.8806del (p.Val2936fs)	Pathogenic
1027908	NM_001369.3(DNAH5):c.12907C>T (p.Gln4303Ter)	Pathogenic
1066241	NM_001369.3(DNAH5):c.9897+1G>A	Pathogenic
1069482	NC_000005.9:g.(?13931209)(13931363_?)del	Pathogenic
1069562	NC_000005.9:g.(?13844936)(13845112_?)del	Pathogenic
1069563	NC_000005.9:g.(?13824302)(13830890_?)del	Pathogenic
1069728	NM_001369.3(DNAH5):c.5769C>G (p.Tyr1923Ter)	Pathogenic
1069773	NM_001369.3(DNAH5):c.1380del (p.Lys460fs)	Pathogenic
1070080	NM_001369.3(DNAH5):c.2752G>T (p.Glu918Ter)	Pathogenic
1070339	NM_001369.3(DNAH5):c.9399T>A (p.Tyr3133Ter)	Pathogenic
1070599	NM_001369.3(DNAH5):c.5883-1G>C	Pathogenic
1070628	NM_001369.3(DNAH5):c.5434del (p.Gln1812fs)	Pathogenic
1070742	NM_001369.3(DNAH5):c.1326C>G (p.Tyr442Ter)	Pathogenic
1071134	NM_001369.3(DNAH5):c.4619_4622del (p.Lys1540fs)	Pathogenic
1071263	NM_001369.3(DNAH5):c.340_358del (p.Phe114fs)	Pathogenic
1071536	NM_001369.3(DNAH5):c.9540del (p.Phe3181fs)	Pathogenic
1072335	NM_001369.3(DNAH5):c.768C>A (p.Cys256Ter)	Pathogenic
1072370	NM_001369.3(DNAH5):c.7526_7527dup (p.Ser2510fs)	Pathogenic
1072914	NM_001369.3(DNAH5):c.11127_11128del (p.Arg3710fs)	Pathogenic
1073093	NM_001369.3(DNAH5):c.4596+1G>T	Pathogenic
1073095	NM_001369.3(DNAH5):c.7437_7450del (p.Leu2480fs)	Pathogenic
1073261	NM_001369.3(DNAH5):c.9877G>T (p.Glu3293Ter)	Pathogenic
1073508	NM_001369.3(DNAH5):c.7455_7456dup (p.Phe2486fs)	Pathogenic
1073620	NM_001369.3(DNAH5):c.13457_13475del (p.Phe4485_Phe4486insTer)	Pathogenic
1073621	NM_001369.3(DNAH5):c.6804del (p.Thr2269fs)	Pathogenic
1073922	NM_001369.3(DNAH5):c.9280A>T (p.Lys3094Ter)	Pathogenic
1074119	NC_000005.10:g.13714619CT[1]	Pathogenic
1074379	NM_001369.3(DNAH5):c.5244del (p.Asn1748fs)	Pathogenic
1074724	NM_001369.3(DNAH5):c.3529C>T (p.Gln1177Ter)	Pathogenic

SpliceAI

12260 predictions. Top by Δscore:

Variant	Effect	Δscore
5:13692136:C:CC	acceptor_gain	1.0000
5:13700638:A:AC	donor_gain	1.0000
5:13700639:C:CC	donor_gain	1.0000
5:13700639:CTA:C	donor_gain	1.0000
5:13700655:AAAT:A	donor_gain	1.0000
5:13700883:A:T	acceptor_gain	1.0000
5:13708121:A:AC	donor_gain	1.0000
5:13708122:C:CC	donor_gain	1.0000
5:13714403:A:AC	donor_gain	1.0000
5:13714404:C:CC	donor_gain	1.0000
5:13714404:CTT:C	donor_gain	1.0000
5:13714619:CT:C	acceptor_gain	1.0000
5:13717309:CAGTA:C	donor_loss	1.0000
5:13717310:AGTAC:A	donor_loss	1.0000
5:13717311:GTACC:G	donor_loss	1.0000
5:13717312:TACCT:T	donor_loss	1.0000
5:13717314:C:CA	donor_loss	1.0000
5:13717532:A:T	acceptor_gain	1.0000
5:13718875:GACTC:G	donor_loss	1.0000
5:13718876:ACTC:A	donor_loss	1.0000
5:13718877:CTCAC:C	donor_loss	1.0000
5:13718878:TCACC:T	donor_loss	1.0000
5:13718879:CA:C	donor_loss	1.0000
5:13718880:A:AC	donor_gain	1.0000
5:13718880:A:AG	donor_loss	1.0000
5:13718881:C:CC	donor_gain	1.0000
5:13718881:CCA:C	donor_gain	1.0000
5:13718881:CCACT:C	donor_gain	1.0000
5:13719100:CC:C	acceptor_gain	1.0000
5:13719101:CC:C	acceptor_gain	1.0000

AlphaMissense

30771 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:13807691:T:A	K2596I	1.000
5:13814659:T:A	R2392S	1.000
5:13814659:T:G	R2392S	1.000
5:13814660:C:A	R2392I	1.000
5:13814660:C:G	R2392T	1.000
5:13814672:G:T	A2388D	1.000
5:13814753:A:G	L2361P	1.000
5:13814759:A:G	L2359P	1.000
5:13814775:C:G	D2354H	1.000
5:13814785:A:C	N2350K	1.000
5:13814785:A:T	N2350K	1.000
5:13814789:A:G	L2349P	1.000
5:13814795:T:A	E2347V	1.000
5:13814802:A:G	W2345R	1.000
5:13814802:A:T	W2345R	1.000
5:13701284:C:A	Q4497H	0.999
5:13701284:C:G	Q4497H	0.999
5:13717404:A:G	W4206R	0.999
5:13717404:A:T	W4206R	0.999
5:13719095:A:G	W4096R	0.999
5:13719095:A:T	W4096R	0.999
5:13776461:C:A	W3117C	0.999
5:13776461:C:G	W3117C	0.999
5:13776463:A:G	W3117R	0.999
5:13776463:A:T	W3117R	0.999
5:13793947:A:G	W2667R	0.999
5:13793947:A:T	W2667R	0.999
5:13814654:C:T	G2394E	0.999
5:13814661:T:C	R2392G	0.999
5:13814664:A:G	S2391P	0.999

dbSNP variants (sampled 300 via entrez): RS1000003751 (5:13851600 G>A,T), RS1000021303 (5:14003164 T>C), RS1000021402 (5:13891403 T>C), RS1000024034 (5:13933880 AC>A), RS1000038807 (5:13784985 G>A), RS1000047685 (5:13865852 G>A,C,T), RS1000058407 (5:13786630 T>C), RS1000071505 (5:14009709 G>A), RS1000082165 (5:14009503 T>C), RS1000093810 (5:13738546 C>T), RS1000099736 (5:13821364 T>C), RS1000114271 (5:13980440 A>G,T), RS1000121908 (5:13781331 T>A), RS1000124893 (5:13738717 A>C), RS1000134537 (5:14009204 G>A)

Disease associations

OMIM: gene MIM:603335 | disease phenotypes: MIM:244400, MIM:608644, MIM:611884, MIM:605899

GenCC curated gene-disease

Disease	Classification	Inheritance
primary ciliary dyskinesia 3	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 3	Definitive	AR

Mondo (8): primary ciliary dyskinesia (MONDO:0016575), primary ciliary dyskinesia 3 (MONDO:0012085), primary ciliary dyskinesia 7 (MONDO:0012748), primary ciliary dyskinesia 1 (MONDO:0009484), infertility disorder (MONDO:0005047), male infertility (MONDO:0005372), situs inversus (MONDO:0010029), glycine encephalopathy 1 (MONDO:0958179)

Orphanet (4): Primary ciliary dyskinesia (Orphanet:244), Situs ambiguus (Orphanet:157769), Situs inversus totalis (Orphanet:101063), Primary ciliary dyskinesia, Kartagener type (Orphanet:98861)

HPO phenotypes

54 total (30 of 54 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: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:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0005301	Persistent left superior vena cava

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST000087_1	Subclinical atherosclerosis traits (other)	6.000000e-06
GCST000087_6	Subclinical atherosclerosis traits (other)	5.000000e-06
GCST000087_7	Subclinical atherosclerosis traits (other)	9.000000e-06
GCST001303_6	IgE grass sensitization	3.000000e-06
GCST001525_35	Visceral fat	7.000000e-06
GCST001819_4	Corneal astigmatism	1.000000e-06
GCST002945_33	Emphysema imaging phenotypes	9.000000e-07
GCST003263_25	Post bronchodilator FEV1 in COPD	1.000000e-06
GCST003265_146	Post bronchodilator FEV1/FVC ratio in COPD	3.000000e-06
GCST003265_147	Post bronchodilator FEV1/FVC ratio in COPD	3.000000e-06
GCST003265_158	Post bronchodilator FEV1/FVC ratio in COPD	2.000000e-06
GCST003265_42	Post bronchodilator FEV1/FVC ratio in COPD	3.000000e-06
GCST003265_43	Post bronchodilator FEV1/FVC ratio in COPD	3.000000e-06
GCST003265_46	Post bronchodilator FEV1/FVC ratio in COPD	4.000000e-06
GCST003265_49	Post bronchodilator FEV1/FVC ratio in COPD	3.000000e-06
GCST003265_51	Post bronchodilator FEV1/FVC ratio in COPD	3.000000e-06
GCST003265_52	Post bronchodilator FEV1/FVC ratio in COPD	3.000000e-06
GCST003265_68	Post bronchodilator FEV1/FVC ratio in COPD	4.000000e-06
GCST003581_1	Toxicity response to radiotherapy in prostate cancer (decreased urine stream) (time to event)	3.000000e-08
GCST005330_1	Coffee consumption	5.000000e-07
GCST007356_4	Antidepressant treatment resistance (number of drugs prescribed)	5.000000e-07
GCST009997_3	Thyroid volume in Hashimoto’s thyroiditis	1.000000e-07
GCST012170_1	Cognitive function in longevity	1.000000e-07
GCST90007000_4	Gut microbiota relative abundance (unclassified genus belonging to family Ruminococcaceae)	6.000000e-06

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0003912	ankle brachial index
EFO:0005278	cardiovascular disease biomarker measurement
EFO:0007626	emphysema imaging measurement
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0006782	cups of coffee per day measurement
EFO:0008354	cognitive function measurement
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (7)

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
D012857	Situs Inversus	C16.131.810
C567504	Ciliary Dyskinesia, Primary, 7 (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

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
Estradiol	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
2-palmitoylglycerol	increases expression	1
NSC 689534	affects binding, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Copper	affects binding, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
DEET	decreases expression	1
Nickel	decreases expression	1
Oxygen	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	increases abundance, increases expression	1
Dihydrotestosterone	increases expression	1
Valproic Acid	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

6 cell lines: 3 cancer cell line, 3 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B1F3	Abcam A-549 DNAH5 KO	Cancer cell line	Male
CVCL_D3BE	PCD1	Induced pluripotent stem cell	Female
CVCL_D7NT	Ubigene A-549 DNAH5 KO	Cancer cell line	Male
CVCL_D8K6	Ubigene HCT 116 DNAH5 KO	Cancer cell line	Male
CVCL_ZJ18	MHHi017-A	Induced pluripotent stem cell	Female
CVCL_ZJ19	MHHi017-B	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

203 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