DNAH11

Summary

DNAH11 (dynein axonemal heavy chain 11, HGNC:2942) is a protein-coding gene on chromosome 7p15.3, encoding Dynein axonemal heavy chain 11 (Q96DT5). Force generating protein required for cilia beating in respiratory epithelia.

This gene encodes a ciliary outer dynein arm protein and is a member of the dynein heavy chain family. It is a microtubule-dependent motor ATPase and has been reported to be involved in the movement of respiratory cilia. Mutations in this gene have been implicated in causing Kartagener Syndrome (a combination of situs inversus totalis and Primary Ciliary Dyskinesia (PCD), also called Immotile Cilia Syndrome 1 (ICS1)) and male sterility.

Source: NCBI Gene 8701 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary ciliary dyskinesia 7 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 49
• Clinical variants (ClinVar): 6,476 total — 353 pathogenic, 152 likely-pathogenic
• Phenotypes (HPO): 58
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001277115

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2942
Approved symbol	DNAH11
Name	dynein axonemal heavy chain 11
Location	7p15.3
Locus type	gene with protein product
Status	Approved
Aliases	Dnahc11, DPL11, CILD7, DNAHC11, DNAHBL, DNHBL
Ensembl gene	ENSG00000105877
Ensembl biotype	protein_coding
OMIM	603339
Entrez	8701

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding_CDS_not_defined, 3 retained_intron, 2 protein_coding

ENST00000409508, ENST00000421290, ENST00000465129, ENST00000465593, ENST00000479878, ENST00000483691, ENST00000496218, ENST00000605912, ENST00000607050, ENST00000607413

RefSeq mRNA: 1 — MANE Select: NM_001277115 NM_001277115

CCDS: CCDS64602

Canonical transcript exons

ENST00000409508 — 82 exons

Exon	Start	End
ENSE00001208952	21681546	21681677
ENSE00001416067	21901007	21901839
ENSE00003540990	21616209	21616292
ENSE00003694918	21600676	21600930
ENSE00003695199	21707699	21707835
ENSE00003695215	21866470	21866663
ENSE00003695294	21725811	21725984
ENSE00003695414	21816467	21816702
ENSE00003695461	21601010	21601179
ENSE00003695517	21801137	21801275
ENSE00003695526	21741927	21742166
ENSE00003695532	21864535	21864657
ENSE00003695674	21818217	21818339
ENSE00003695780	21735640	21735844
ENSE00003695927	21615114	21615272
ENSE00003695956	21739571	21739673
ENSE00003696125	21690765	21690881
ENSE00003696156	21601396	21601618
ENSE00003696179	21658798	21659031
ENSE00003696204	21892425	21892667
ENSE00003696245	21744870	21745063
ENSE00003696289	21635871	21636095
ENSE00003696350	21894623	21894805
ENSE00003696384	21861853	21862023
ENSE00003696531	21899980	21900120
ENSE00003696545	21784427	21784540
ENSE00003696573	21786624	21786767
ENSE00003696682	21710553	21710703
ENSE00003696814	21711712	21711860
ENSE00003696823	21655832	21655981
ENSE00003696903	21750222	21750364
ENSE00003696915	21702710	21702802
ENSE00003696974	21588512	21588636
ENSE00003696987	21570069	21570299
ENSE00003697006	21619956	21620078
ENSE00003697074	21687099	21687255
ENSE00003697300	21873274	21873501
ENSE00003697489	21704434	21704628
ENSE00003697546	21868864	21868991
ENSE00003697627	21588064	21588201
ENSE00003697924	21606426	21606542
ENSE00003697945	21705460	21705537
ENSE00003698224	21778958	21779104
ENSE00003698432	21564186	21564397
ENSE00003698632	21638939	21639065
ENSE00003698725	21637611	21637702
ENSE00003698782	21807883	21808049
ENSE00003699104	21880702	21880893
ENSE00003699325	21787401	21787583
ENSE00003699401	21854315	21854455
ENSE00003699544	21789241	21789342
ENSE00003699593	21619100	21619222
ENSE00003699594	21561071	21561170
ENSE00003699685	21748580	21748742
ENSE00003699746	21571806	21571973
ENSE00003699759	21606647	21606733
ENSE00003699771	21698075	21698213
ENSE00003699891	21589208	21589403
ENSE00003699966	21744438	21744599
ENSE00003699985	21884291	21884410
ENSE00003700061	21842544	21842748
ENSE00003700225	21590918	21591022
ENSE00003700233	21738701	21738866
ENSE00003700285	21599787	21600119
ENSE00003700529	21558802	21558998
ENSE00003700547	21899336	21899448
ENSE00003700580	21717775	21717925
ENSE00003700640	21720725	21720856
ENSE00003700655	21581905	21582021
ENSE00003700686	21894884	21894999
ENSE00003700902	21617619	21617777
ENSE00003701098	21765428	21765589
ENSE00003701311	21591185	21591577
ENSE00003701586	21867859	21868007
ENSE00003701719	21749678	21749801
ENSE00003701868	21852467	21852631
ENSE00003701974	21773766	21773999
ENSE00003702057	21545006	21545149
ENSE00003702146	21687382	21687527
ENSE00003702159	21683784	21683944
ENSE00003702436	21559603	21559792
ENSE00003842356	21543039	21543596

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 96.37.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9217 / max 122.7252, expressed in 304 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
77556	0.9217	304

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	96.37	gold quality
bronchial epithelial cell	CL:0002328	93.50	gold quality
bronchus	UBERON:0002185	91.99	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.09	gold quality
right adrenal gland cortex	UBERON:0035827	87.34	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.29	gold quality
right adrenal gland	UBERON:0001233	85.77	gold quality
caput epididymis	UBERON:0004358	83.85	gold quality
left adrenal gland	UBERON:0001234	83.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.16	gold quality
left adrenal gland cortex	UBERON:0035825	82.70	gold quality
adrenal cortex	UBERON:0001235	82.09	gold quality
adrenal gland	UBERON:0002369	80.68	gold quality
oviduct epithelium	UBERON:0004804	80.35	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.40	gold quality
fallopian tube	UBERON:0003889	77.85	gold quality
lower esophagus muscularis layer	UBERON:0035833	77.24	gold quality
lower esophagus	UBERON:0013473	77.19	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	74.44	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	74.22	gold quality
lower esophagus mucosa	UBERON:0035834	74.19	gold quality
superficial temporal artery	UBERON:0001614	74.06	gold quality
epithelium of nasopharynx	UBERON:0001951	73.80	silver quality
buccal mucosa cell	CL:0002336	72.86	silver quality
right lung	UBERON:0002167	72.72	gold quality
left uterine tube	UBERON:0001303	71.91	gold quality
nasal cavity epithelium	UBERON:0005384	71.16	gold quality
cauda epididymis	UBERON:0004360	70.95	silver quality
calcaneal tendon	UBERON:0003701	70.93	gold quality
esophagus	UBERON:0001043	70.35	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	2160.31
E-ANND-3	yes	10.39

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXJ1

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 22)

• mutations in the DNAH11 gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia (PMID:12142464)
• Dynein plays an unexpected role in the regulation of mitochondrial morphology in living cells, by controlling the recruitment of Drp1 to these organelles. (PMID:15304525)
• a specific requirement for p150(Glued)/dynein/functional microtubules in activation of MKK3/6 and p38 MAPKs in vivo. (PMID:15375157)
• These findings support the view that DNAH11 mutations indeed cause Primary ciliary dyskinesia and Kartagener syndrome, and that the reported DNAH11 nonsense mutations are associated with a normal axonemal ultrastructure. (PMID:18022865)
• Two “major” genes, DNAI1 and DNAH5, underlie PCD in nearly half of the patients with ODA defects (PMID:19410201)
• mutations: splice site in acceptor splice site of exon 5 and nonsense mutation located in exon 23 for DNAH11 in primary ciliary dyskinesia (PMID:20513915)
• Mutations in DNAH11 are a common cause of PCD in patients without ciliary ultrastructural defects; thus, genetic analysis can be used to ascertain the diagnosis of PCD in this challenging group of patients. (PMID:22184204)
• In an epithelial cell line engineered to contain the DNAH11 target site, TALENs cleaved over 80% of the mutated DNAH11 sequence and replaced the mutated sequence with wild-type sequence in about 50% of cells. This study demonstrates that gene editing can rescue ciliary beating ex vivo, opening up new avenues for treating Primary ciliary dyskinesia. (PMID:26729821)
• DNAH11 mutations result in a subtle outer dynein arm defect in only the proximal region of respiratory cilia. (PMID:26909801)
• Dnah11(avc)(4) did not disrupt SHF Hh signaling and caused Atrioventricular septal defects (AVSDs) only concurrently with heterotaxy, a left/right axis abnormality. In contrast, Mks1(avc)(6) disrupted SHF Hh signaling and caused AVSDs without heterotaxy.We speculate that cilia gene mutations contribute to both syndromic and non-syndromic AVSDs in humans (PMID:27340223)
• DNAH11 mutations result in a characteristic abnormality of the ciliary ultrastructure detectable by electron tomography, but not traditional transmission electron microscopy (PMID:29467202)
• DNAH11 variants and its association with congenital heart disease and heterotaxy syndrome. (PMID:31040315)
• study demonstrated that the polymorphisms rs2494938 at 6p21.1 and rs2285947 at 7p15.3 may serve as independent prognostic biomarkers for ESCC, implying the potential biological role of their related genes (LRFN2 and DNAH11) in the process of ESCC development (PMID:31053115)
• The variant c.9484-1 G>T was confirmed as a novel virulence variant which was predicted to affect splicing by Human Splicing Finder 3.1. And c.12428 T>C was predicted to be mildly pathogenic in silico analysis. We found that DNAH11 polymorphisms display strong associations with asthenozoospermia, and may contribute to an increased risk of male infertility in Chinese patients. (PMID:31160482)
• The rs2285947 variant of DNAH11 was found to be significantly associated with both ovarian and breast cancers in a cohort of women in India. (PMID:31605628)
• 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)
• Two novel mutations in the DNAH11 gene in primary ciliary dyskinesia (CILD7) with considerable variety in the clinical and beating cilia phenotype. (PMID:33243178)
• DNAH11 compound heterozygous variants cause heterotaxy and congenital heart disease. (PMID:34133440)
• Identification of compound heterozygous DNAH11 variants in a Han-Chinese family with primary ciliary dyskinesia. (PMID:34405951)
• Clustering of Genetic Anomalies of Cilia Outer Dynein Arm and Central Apparatus in Patients with Transposition of the Great Arteries. (PMID:36140829)
• A Deep Intronic, Pathogenic Variant in DNAH11 Causes Primary Ciliary Dyskinesia. (PMID:36178856)
• First reports of primary ciliary dyskinesia caused by a shared DNAH11 allele in Canadian Inuit. (PMID:37088965)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000077384
danio_rerio	dnah11	ENSDARG00000094282
mus_musculus	Dnah11	ENSMUSG00000018581
rattus_norvegicus	Dnah11	ENSRNOG00000005451

Paralogs (15): DNAH9 (ENSG00000007174), DNAH5 (ENSG00000039139), 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 11 — Q96DT5 (reviewed: Q96DT5)

Alternative names: Axonemal beta dynein heavy chain 11, Ciliary dynein heavy chain 11

All UniProt accessions (2): Q96DT5, U3KQN2

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 CFAP45.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme.

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

Disease relevance. Ciliary dyskinesia, primary, 7 (CILD7) [MIM:611884] 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_001264044* (*=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 (37 total): sequence variant 20, region of interest 8, coiled-coil region 4, binding site 4, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q96DT5 — 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): 1893–1900; 2174–2181; 2510–2517; 2855–2862

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 203 (showing top): GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, MODULE_255, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, MODULE_317, GOBP_SPECIFICATION_OF_SYMMETRY, NF1_Q6_01, MODULE_256, GOBP_CILIUM_MOVEMENT, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY, MODULE_301, GOBP_REGULATION_OF_MICROTUBULE_BASED_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GATA1_03

GO Biological Process (13): regulation of cilium beat frequency (GO:0003356), determination of left/right symmetry (GO:0007368), learning or memory (GO:0007611), flagellated sperm motility (GO:0030317), determination of left/right asymmetry in nervous system (GO:0035545), epithelial cilium movement involved in determination of left/right asymmetry (GO:0060287), cilium movement involved in cell motility (GO:0060294), cardiac septum morphogenesis (GO:0060411), protein localization to motile cilium (GO:0120229), cilium movement (GO:0003341), epithelial cilium movement involved in extracellular fluid movement (GO:0003351), microtubule-based movement (GO:0007018), heart development (GO:0007507)

GO Molecular Function (6): 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), ATP hydrolysis activity (GO:0016887)

GO Cellular Component (12): extracellular region (GO:0005576), microtubule (GO:0005874), axoneme (GO:0005930), dynein complex (GO:0030286), motile cilium (GO:0031514), 9+0 motile cilium (GO:0097728), 9+2 motile cilium (GO:0097729), proximal portion of axoneme (GO:0120134), 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
cilium-dependent cell motility	2
determination of left/right symmetry	2
cilium movement	2
protein binding	2
motile cilium	2
inner dynein arm	2
outer dynein arm	2
axonemal doublet microtubule	2
regulation of cilium movement	1
determination of bilateral symmetry	1
left/right pattern formation	1
behavior	1
cognition	1
cilium movement involved in cell motility	1
sperm motility	1
nervous system development	1
epithelial cilium movement involved in extracellular fluid movement	1
cell motility	1
cardiac chamber morphogenesis	1
cardiac septum development	1
anatomical structure morphogenesis	1
protein localization to cilium	1
microtubule-based movement	1
extracellular transport	1
microtubule-based transport	1
microtubule-based process	1
animal organ development	1
circulatory system development	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
microtubule motor activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
cytoskeleton	1
microtubule	1

Protein interactions and networks

STRING

1650 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAH11	DNAI1	Q9UI46	975
DNAH11	DNAI2	Q9GZS0	964
DNAH11	RSPH4A	Q5TD94	922
DNAH11	RSPH9	Q9H1X1	918
DNAH11	NME8	Q8N427	910
DNAH11	DNAAF1	Q8NEP3	899
DNAH11	DNAAF2	Q9NVR5	898
DNAH11	CCDC40	Q4G0X9	804
DNAH11	CCDC39	Q9UFE4	802
DNAH11	SP8	Q8IXZ3	778
DNAH11	ODAD1	Q96M63	771
DNAH11	RPGR	Q92834	749
DNAH11	DNAAF11	Q86X45	748
DNAH11	ODAD2	Q5T2S8	736
DNAH11	DNAAF19	Q8IW40	735

IntAct

0 interactions, top by confidence:

BioGRID (16): DNAH11 (Two-hybrid), DNAH11 (Affinity Capture-Western), DNAH11 (Affinity Capture-MS), DNAH11 (Proximity Label-MS), DNAH11 (Affinity Capture-MS), DNAH11 (Affinity Capture-MS), DNAH11 (Protein-peptide), DNAH11 (Affinity Capture-MS), DNAH17 (Negative Genetic), DNAH11 (Proximity Label-MS), DNAH11 (Proximity Label-MS), DNAH11 (Cross-Linking-MS (XL-MS)), DNAH11 (Cross-Linking-MS (XL-MS)), RAB29 (Cross-Linking-MS (XL-MS)), DNAH11 (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, P34036, P37276, P38650, P45443, P45444, P78716, Q14204, Q19020, Q27171

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
FOXJ1	“up-regulates quantity by expression”	DNAH11	“transcriptional regulation”
CFAP53	“up-regulates activity”	DNAH11	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

6476 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	353
Likely pathogenic	152
Uncertain significance	1123
Likely benign	2865
Benign	964

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012303	NM_001277115.2(DNAH11):c.7441-1G>C	Pathogenic
1012304	NM_001277115.2(DNAH11):c.8769_8785del (p.Val2924fs)	Pathogenic
1012320	NM_001277115.2(DNAH11):c.9454A>T (p.Lys3152Ter)	Pathogenic
1030335	NM_001277115.2(DNAH11):c.3223C>T (p.Gln1075Ter)	Pathogenic
1066542	NM_001277115.2(DNAH11):c.4254+5G>C	Pathogenic
1067300	NM_001277115.2(DNAH11):c.2671A>G (p.Asn891Asp)	Pathogenic
1068616	NM_001277115.2(DNAH11):c.1475_1593+946del	Pathogenic
1068707	NM_001277115.2(DNAH11):c.11188C>T (p.Gln3730Ter)	Pathogenic
1070658	NM_001277115.2(DNAH11):c.1320del (p.Lys440fs)	Pathogenic
1073225	NM_001277115.2(DNAH11):c.5218C>T (p.Gln1740Ter)	Pathogenic
1073724	NM_001277115.2(DNAH11):c.8076_8077del (p.Met2693fs)	Pathogenic
1073850	NM_001277115.2(DNAH11):c.9478C>T (p.Arg3160Ter)	Pathogenic
1074149	NM_001277115.2(DNAH11):c.13266_13272dup (p.Gly4425fs)	Pathogenic
1076012	NM_001277115.2(DNAH11):c.5924+2T>A	Pathogenic
1210044	NM_001277115.2(DNAH11):c.13103_13104del (p.Leu4368fs)	Pathogenic
1338961	NM_001277115.2(DNAH11):c.9451G>T (p.Glu3151Ter)	Pathogenic
1363554	NM_001277115.2(DNAH11):c.8709del (p.Lys2904fs)	Pathogenic
1386377	NM_001277115.2(DNAH11):c.13096C>T (p.Gln4366Ter)	Pathogenic
1389066	NM_001277115.2(DNAH11):c.10883del (p.Leu3628fs)	Pathogenic
1408912	NM_001277115.2(DNAH11):c.10153G>T (p.Glu3385Ter)	Pathogenic
1426697	NM_001277115.2(DNAH11):c.8444T>G (p.Leu2815Ter)	Pathogenic
1426708	NM_001277115.2(DNAH11):c.9896G>C (p.Trp3299Ser)	Pathogenic
1432278	NM_001277115.2(DNAH11):c.5622-1G>T	Pathogenic
1433676	NM_001277115.2(DNAH11):c.3901G>T (p.Glu1301Ter)	Pathogenic
1451183	NC_000007.14:g.21894887del	Pathogenic
1452056	NM_001277115.2(DNAH11):c.3020T>G (p.Leu1007Ter)	Pathogenic
1453371	NM_001277115.2(DNAH11):c.2406G>A (p.Trp802Ter)	Pathogenic
1453636	NM_001277115.2(DNAH11):c.7981del (p.Ile2661fs)	Pathogenic
1453659	NM_001277115.2(DNAH11):c.5845del (p.Arg1949fs)	Pathogenic
1453708	NM_001277115.2(DNAH11):c.13242_13245del (p.Glu4416fs)	Pathogenic

SpliceAI

13950 predictions. Top by Δscore:

Variant	Effect	Δscore
7:21558999:G:GG	donor_gain	1.0000
7:21559592:AAT:A	acceptor_gain	1.0000
7:21559600:TA:T	acceptor_loss	1.0000
7:21559601:A:AG	acceptor_gain	1.0000
7:21559602:G:GA	acceptor_gain	1.0000
7:21559602:GGCC:G	acceptor_gain	1.0000
7:21559602:GGCCA:G	acceptor_gain	1.0000
7:21561064:A:AG	acceptor_gain	1.0000
7:21561069:A:AG	acceptor_gain	1.0000
7:21561070:G:GC	acceptor_gain	1.0000
7:21561070:GCT:G	acceptor_gain	1.0000
7:21561070:GCTT:G	acceptor_gain	1.0000
7:21561070:GCTTC:G	acceptor_gain	1.0000
7:21564184:A:AG	acceptor_gain	1.0000
7:21564185:G:GG	acceptor_gain	1.0000
7:21581899:TTACA:T	acceptor_loss	1.0000
7:21581900:TACA:T	acceptor_loss	1.0000
7:21581902:CA:C	acceptor_loss	1.0000
7:21581904:GGA:G	acceptor_gain	1.0000
7:21582017:TTAAG:T	donor_loss	1.0000
7:21582018:TAAG:T	donor_loss	1.0000
7:21582019:AAGGT:A	donor_loss	1.0000
7:21582020:AGGTT:A	donor_loss	1.0000
7:21582021:GG:G	donor_loss	1.0000
7:21582022:G:GA	donor_loss	1.0000
7:21582023:T:A	donor_loss	1.0000
7:21588062:A:AG	acceptor_gain	1.0000
7:21588063:G:GG	acceptor_gain	1.0000
7:21588203:T:A	donor_loss	1.0000
7:21588492:A:AG	acceptor_gain	1.0000

AlphaMissense

29969 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:21687234:T:G	C1919W	0.997
7:21687449:G:C	R1949P	0.997
7:21690828:C:A	N1996K	0.997
7:21690828:C:G	N1996K	0.997
7:21710665:T:A	W2266R	0.997
7:21710665:T:C	W2266R	0.997
7:21687173:A:T	K1899I	0.996
7:21687424:T:A	W1941R	0.996
7:21687424:T:C	W1941R	0.996
7:21687436:G:C	D1945H	0.996
7:21687437:A:C	D1945A	0.996
7:21687437:A:T	D1945V	0.996
7:21687439:G:A	E1946K	0.996
7:21687440:A:T	E1946V	0.996
7:21710682:T:A	N2271K	0.996
7:21710682:T:G	N2271K	0.996
7:21711803:C:A	A2309D	0.996
7:21711815:G:C	R2313T	0.996
7:21711815:G:T	R2313I	0.996
7:21765527:T:A	W3014R	0.996
7:21765527:T:C	W3014R	0.996
7:21687172:A:C	K1899Q	0.995
7:21687447:C:A	N1948K	0.995
7:21687447:C:G	N1948K	0.995
7:21687232:T:C	C1919R	0.994
7:21687440:A:C	E1946A	0.994
7:21687441:G:C	E1946D	0.994
7:21687441:G:T	E1946D	0.994
7:21690854:T:C	L2005S	0.994
7:21710692:G:C	D2275H	0.994

dbSNP variants (sampled 300 via entrez): RS1000001498 (7:21796434 T>A,C), RS1000004956 (7:21795715 C>T), RS1000006497 (7:21603861 C>T), RS1000009004 (7:21825095 T>A), RS1000010649 (7:21635292 G>A), RS1000013690 (7:21764795 A>G), RS1000014905 (7:21667388 A>G), RS1000024158 (7:21769451 A>C,G), RS1000031573 (7:21888787 C>T), RS1000032278 (7:21576128 C>T), RS1000038608 (7:21690300 G>C), RS1000048201 (7:21808437 T>C), RS1000059365 (7:21596083 T>G), RS1000060788 (7:21899029 T>C), RS1000064719 (7:21703122 T>C)

Disease associations

OMIM: gene MIM:603339 | disease phenotypes: MIM:244400, MIM:611884, MIM:601086, MIM:615444, MIM:617577, MIM:608644

GenCC curated gene-disease

Disease	Classification	Inheritance
primary ciliary dyskinesia 7	Definitive	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 7	Definitive	AR

Mondo (13): primary ciliary dyskinesia (MONDO:0016575), primary ciliary dyskinesia 7 (MONDO:0012748), primary ciliary dyskinesia 1 (MONDO:0009484), laterality defects, autosomal dominant (MONDO:0010991), primary ciliary dyskinesia 22 (MONDO:0014192), situs inversus (MONDO:0010029), developmental defect during embryogenesis (MONDO:0019755), primary ovarian failure (MONDO:0005387), congenital portosystemic shunt (MONDO:0018811), ciliary dyskinesia, primary, 37 (MONDO:0033204), infertility disorder (MONDO:0005047), male infertility (MONDO:0005372), primary ciliary dyskinesia 3 (MONDO:0012085)

Orphanet (7): Primary ciliary dyskinesia (Orphanet:244), Visceral heterotaxy (Orphanet:450), Situs inversus totalis (Orphanet:101063), Rare developmental defect during embryogenesis (Orphanet:93890), Congenital portosystemic shunt (Orphanet:480531), Primary ciliary dyskinesia, Kartagener type (Orphanet:98861), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

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: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:0001651	Dextrocardia
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:0002091	Restrictive ventilatory defect
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:0005301	Persistent left superior vena cava
HP:0005425	Recurrent sinopulmonary infections

GWAS associations

49 associations (top):

Study	Trait	p-value
GCST000282_4	LDL cholesterol	6.000000e-09
GCST000285_2	Cholesterol, total	9.000000e-07
GCST000759_7	LDL cholesterol	7.000000e-10
GCST000760_3	Cholesterol, total	7.000000e-10
GCST000891_2	Whole-brain volume	4.000000e-06
GCST000898_6	Total ventricular volume	2.000000e-06
GCST001331_1	Multiple myeloma	3.000000e-14
GCST001718_1	Multiple cancers (lung cancer, gastric cancer, and squamous cell carcinoma)	3.000000e-06
GCST001718_5	Multiple cancers (lung cancer, gastric cancer, and squamous cell carcinoma)	2.000000e-08
GCST001718_6	Multiple cancers (lung cancer, gastric cancer, and squamous cell carcinoma)	1.000000e-06
GCST001718_7	Multiple cancers (lung cancer, gastric cancer, and squamous cell carcinoma)	1.000000e-16
GCST002221_25	Cholesterol, total	1.000000e-16
GCST002222_4	LDL cholesterol	5.000000e-14
GCST002320_6	Cognitive decline (age-related)	4.000000e-06
GCST002896_30	Cholesterol, total	4.000000e-13
GCST002898_31	LDL cholesterol	2.000000e-14
GCST002921_6	Multiple myeloma	4.000000e-08
GCST002922_7	Multiple myeloma and monoclonal gammopathy	2.000000e-08
GCST004233_12	LDL cholesterol levels	2.000000e-12
GCST004235_68	Total cholesterol levels	5.000000e-15
GCST004988_679	Breast cancer	2.000000e-08
GCST006444_12	Bone mineral density (hip)	3.000000e-06
GCST006612_20	LDL cholesterol	2.000000e-16
GCST006614_133	Total cholesterol levels	9.000000e-19
GCST007922_3	Medication use (drugs for peptic ulcer and gastro-oesophageal reflux disease)	9.000000e-11
GCST007931_32	Medication use (HMG CoA reductase inhibitors)	4.000000e-15
GCST008078_4	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	6.000000e-23
GCST008078_65	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-24
GCST008079_50	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5.000000e-27
GCST008079_9	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-25

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0005089	whole-brain volume
EFO:0007702	hip bone mineral density
EFO:0009923	Peptic ulcer and gastro-oesophageal reflux disease (GORD) drug use measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0004329	alcohol drinking
EFO:0010516	orotic acid measurement
EFO:0008529	kynurenine measurement
EFO:0004615	apolipoprotein B measurement
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0010733	polyunsaturated fatty acid measurement
EFO:0004462	PR interval
EFO:0004346	neuroimaging measurement
EFO:0008343	sex interaction measurement
EFO:0004531	urate measurement
EFO:0007874	gut microbiome 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
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
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D012857	Situs Inversus	C16.131.810
C567504	Ciliary Dyskinesia, Primary, 7 (supp.)
C563391	Laterality Defects, Autosomal Dominant (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

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	2
Oxygen	increases expression	2
Smoke	increases expression, decreases expression, increases abundance	2
Tobacco Smoke Pollution	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
sotorasib	affects cotreatment, decreases expression	1
methyleugenol	decreases expression	1
arsenite	increases expression, decreases methylation	1
nickel sulfate	increases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Sunitinib	increases expression	1
Ethanol	affects cotreatment, increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Clozapine	affects cotreatment, decreases expression	1
Cuprizone	affects cotreatment, decreases expression, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Folic Acid	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Vanadates	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
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
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
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
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
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
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
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
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI