DNAAF11

Summary

DNAAF11 (dynein axonemal assembly factor 11, HGNC:16725) is a protein-coding gene on chromosome 8q24.22, encoding Dynein axonemal assembly factor 11 (Q86X45). Involved in dynein arm assembly, is important for expression and transporting outer dynein arm (ODA) proteins from the cytoplasm to the cilia.

The protein encoded by this gene contains several leucine-rich repeat domains and appears to be involved in the motility of cilia. Defects in this gene are a cause of primary ciliary dyskinesia-19 (CILD19). Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 4, 11 and 22.

Source: NCBI Gene 23639 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary ciliary dyskinesia 19 (Definitive, ClinGen)
• Clinical variants (ClinVar): 363 total — 34 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 56
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_012472

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16725
Approved symbol	DNAAF11
Name	dynein axonemal assembly factor 11
Location	8q24.22
Locus type	gene with protein product
Status	Approved
Aliases	TSLRP, LRTP, CILD19, tilB
Ensembl gene	ENSG00000129295
Ensembl biotype	protein_coding
OMIM	614930
Entrez	23639

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 13 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000250173, ENST00000518101, ENST00000518642, ENST00000519085, ENST00000519595, ENST00000520446, ENST00000521430, ENST00000522584, ENST00000522597, ENST00000522789, ENST00000523503, ENST00000620350, ENST00000869718, ENST00000869719, ENST00000869720, ENST00000940684, ENST00000940685, ENST00000940686, ENST00000940687

RefSeq mRNA: 7 — MANE Select: NM_012472 NM_001321961, NM_001321962, NM_001321963, NM_001321964, NM_001321965, NM_001321966, NM_012472

CCDS: CCDS6365

Canonical transcript exons

ENST00000620350 — 12 exons

Exon	Start	End
ENSE00001258508	132675484	132675545
ENSE00003536507	132656830	132656907
ENSE00003537974	132615038	132615097
ENSE00003540144	132611294	132611363
ENSE00003544556	132625272	132625454
ENSE00003593550	132661460	132661627
ENSE00003632220	132637935	132638107
ENSE00003843398	132570416	132572480
ENSE00003890329	132583694	132583779
ENSE00003890630	132622611	132622688
ENSE00003892905	132610166	132610261
ENSE00003894900	132632740	132632963

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 97.26.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1862 / max 71.7681, expressed in 805 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95060	1.1816	559
95062	0.4917	243
95061	0.3764	179
95059	0.0976	45
95056	0.0146	7
95057	0.0141	5
95058	0.0101	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.26	gold quality
bronchial epithelial cell	CL:0002328	96.16	gold quality
epithelium of bronchus	UBERON:0002031	94.61	gold quality
bronchus	UBERON:0002185	93.49	gold quality
sperm	CL:0000019	92.40	gold quality
male germ cell	CL:0000015	90.36	gold quality
left testis	UBERON:0004533	90.33	gold quality
right testis	UBERON:0004534	89.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.32	gold quality
testis	UBERON:0000473	88.55	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.34	gold quality
buccal mucosa cell	CL:0002336	87.11	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.35	gold quality
middle temporal gyrus	UBERON:0002771	85.31	gold quality
calcaneal tendon	UBERON:0003701	85.10	gold quality
right frontal lobe	UBERON:0002810	85.07	gold quality
Brodmann (1909) area 23	UBERON:0013554	84.91	gold quality
adenohypophysis	UBERON:0002196	84.67	gold quality
choroid plexus epithelium	UBERON:0003911	84.30	gold quality
adrenal tissue	UBERON:0018303	84.25	gold quality
metanephros cortex	UBERON:0010533	83.84	gold quality
caudate nucleus	UBERON:0001873	83.77	gold quality
nucleus accumbens	UBERON:0001882	83.63	gold quality
left lobe of thyroid gland	UBERON:0001120	83.62	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.60	gold quality
primary visual cortex	UBERON:0002436	83.18	gold quality
thyroid gland	UBERON:0002046	83.17	gold quality
right lobe of thyroid gland	UBERON:0001119	83.03	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.91	gold quality
pituitary gland	UBERON:0000007	82.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

137 targeting DNAAF11, 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-6873-3P	100.00	71.42	2626
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-302E	99.96	70.74	2669

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 5)

• Loss-of-function mutations in LRRC6, a gene essential for proper axonemal assembly of inner and outer dynein arms, cause primary ciliary dyskinesia. (PMID:23122589)
• LRRC6 plays a role in dynein arm assembly or trafficking and when mutated leads to primary ciliary dyskinesia with laterality defects. (PMID:23527195)
• ZMYND10 is mutated in primary ciliary dyskinesia and interacts with LRRC6. (PMID:23891469)
• Our study not only further supported the importance of LRRC6 in Primary ciliary dyskinesia (PCD), but also expanded the spectrum of LRRC6 mutations and will contribute to the genetic diagnosis and counseling of PCD patients. (PMID:29511670)
• Identification of novel biallelic LRRC6 variants in male Chinese patients with primary ciliary dyskinesia and infertility. (PMID:36515799)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnaaf11	ENSDARG00000053318
mus_musculus	Dnaaf11	ENSMUSG00000022375
rattus_norvegicus	Dnaaf11	ENSRNOG00000005233
drosophila_melanogaster	tilB	FBGN0014395

Paralogs (13): LRRC23 (ENSG00000010626), LRRC61 (ENSG00000127399), LRRC9 (ENSG00000131951), LRRCC1 (ENSG00000133739), LRRC49 (ENSG00000137821), LRRC46 (ENSG00000141294), DNAAF1 (ENSG00000154099), LRGUK (ENSG00000155530), LRRC43 (ENSG00000158113), LRRIQ3 (ENSG00000162620), DRC3 (ENSG00000171962), PPP1R42 (ENSG00000178125), CEP97 (ENSG00000182504)

Protein

Protein identifiers

Dynein axonemal assembly factor 11 — Q86X45 (reviewed: Q86X45)

Alternative names: Leucine-rich repeat-containing protein 6, Leucine-rich testis-specific protein, Protein tilB homolog, Testis-specific leucine-rich repeat protein

All UniProt accessions (5): Q86X45, E5RHF9, G5EA20, H0YAS5, H0YBC4

UniProt curated annotations — full annotation on UniProt →

Function. Involved in dynein arm assembly, is important for expression and transporting outer dynein arm (ODA) proteins from the cytoplasm to the cilia. Acts as a crucial component in the formation and motility of spermatozoal flagella.

Subunit / interactions. Interacts (via CS domain) with ZMYND10 (via C-terminus).

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

Tissue specificity. Expressed predominantly in testis and in nasal epithelial cells.

Disease relevance. Ciliary dyskinesia, primary, 19 (CILD19) [MIM:614935] 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.

Similarity. Belongs to the tilB family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86X45-1	1	yes
Q86X45-2	2

RefSeq proteins (7): NP_001308890, NP_001308891, NP_001308892, NP_001308893, NP_001308894, NP_001308895, NP_036604* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR003603	U2A’_phosphoprotein32A_C	Domain
IPR007052	CS_dom	Domain
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR056496	CS_DNAAF11_C	Domain

Pfam: PF14580, PF23602

UniProt features (29 total): sequence variant 9, compositionally biased region 5, repeat 4, region of interest 3, splice variant 2, sequence conflict 2, domain 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86X45-F1	74.44	0.25

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 214 (showing top): GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_INNER_DYNEIN_ARM_ASSEMBLY, GOBP_AXONEMAL_DYNEIN_COMPLEX_ASSEMBLY, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_OUTER_DYNEIN_ARM_ASSEMBLY, GOBP_ORGANELLE_ASSEMBLY, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_SEX_DIFFERENTIATION, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MOTILE_CILIUM_ASSEMBLY

GO Biological Process (15): cilium movement (GO:0003341), epithelial cilium movement involved in extracellular fluid movement (GO:0003351), male gonad development (GO:0008584), actin cytoskeleton organization (GO:0030036), flagellated sperm motility (GO:0030317), outer dynein arm assembly (GO:0036158), inner dynein arm assembly (GO:0036159), motile cilium assembly (GO:0044458), establishment of localization in cell (GO:0051649), epithelial cilium movement involved in determination of left/right asymmetry (GO:0060287), reproductive system development (GO:0061458), protein localization to cilium (GO:0061512), axonemal dynein complex assembly (GO:0070286), cerebrospinal fluid circulation (GO:0090660), protein localization to motile cilium (GO:0120229)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (8): extracellular region (GO:0005576), cytoplasm (GO:0005737), cytosol (GO:0005829), cilium (GO:0005929), motile cilium (GO:0031514), apical cytoplasm (GO:0090651), dynein axonemal particle (GO:0120293), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	3
axonemal dynein complex assembly	2
epithelial cilium movement involved in extracellular fluid movement	2
microtubule-based movement	1
cilium movement	1
extracellular transport	1
microtubule-based transport	1
gonad development	1
development of primary male sexual characteristics	1
cytoskeleton organization	1
actin filament-based process	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
cilium assembly	1
establishment of localization	1
cellular localization	1
determination of left/right symmetry	1
system development	1
protein localization to organelle	1
axoneme assembly	1
protein-containing complex assembly	1
nervous system process	1
protein localization to cilium	1
binding	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1
apical part of cell	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1268 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAAF11	ZMYND10	O75800	932
DNAAF11	DNAAF3	Q8N9W5	854
DNAAF11	DNAAF6	Q9NQM4	848
DNAAF11	DNAAF5	Q86Y56	844
DNAAF11	DNAAF19	Q8IW40	832
DNAAF11	CCDC40	Q4G0X9	812
DNAAF11	DNAAF4	Q8WXU2	811
DNAAF11	CCDC39	Q9UFE4	804
DNAAF11	CFAP298	P57076	803
DNAAF11	SPAG1	Q07617	799
DNAAF11	DNAI1	Q9UI46	792
DNAAF11	DNAI2	Q9GZS0	780
DNAAF11	ODAD2	Q5T2S8	778
DNAAF11	DNAAF2	Q9NVR5	770
DNAAF11	DRC2	Q8IXS2	766

IntAct

39 interactions, top by confidence:

A	B	Type	Score
DNAAF11	SSX7	psi-mi:“MI:0915”(physical association)	0.560
DNAAF11	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
LSM2	DNAAF11	psi-mi:“MI:0915”(physical association)	0.560
DNAAF11	PODN	psi-mi:“MI:0915”(physical association)	0.560
DDX6	DNAAF11	psi-mi:“MI:0915”(physical association)	0.560
TTC23L	DNAAF11	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	DNAAF11	psi-mi:“MI:0915”(physical association)	0.560
DNAAF11	LRCH3	psi-mi:“MI:0915”(physical association)	0.560
SSX7	DNAAF11	psi-mi:“MI:0915”(physical association)	0.560
DNAAF11	LSM2	psi-mi:“MI:0915”(physical association)	0.560
PODN	DNAAF11	psi-mi:“MI:0915”(physical association)	0.560
TERF1	DNAAF11	psi-mi:“MI:0915”(physical association)	0.560
SCRIB	DNAAF11	psi-mi:“MI:0915”(physical association)	0.560
DNAAF11	PPP1R7	psi-mi:“MI:0915”(physical association)	0.530
DNAAF11	CHEK1	psi-mi:“MI:0914”(association)	0.530
PRAMEF17	AIP	psi-mi:“MI:0914”(association)	0.530
DNAAF11	EZR	psi-mi:“MI:0915”(physical association)	0.400
	DNAAF11	psi-mi:“MI:0915”(physical association)	0.400
HSF2	DNAAF11	psi-mi:“MI:0915”(physical association)	0.400
DNAAF11		psi-mi:“MI:0915”(physical association)	0.370
PPP1R7	DNAAF11	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): CACYBP (Co-fractionation), LRRC6 (Two-hybrid), SCRIB (Affinity Capture-MS), PHLPP2 (Affinity Capture-MS), CHEK1 (Affinity Capture-MS), DHPS (Affinity Capture-MS), LRRC6 (Affinity Capture-MS), LRRC6 (Two-hybrid), LRRC6 (Two-hybrid), TERF1 (Two-hybrid), PODN (Two-hybrid), PLEKHF2 (Two-hybrid), LRCH3 (Two-hybrid), SSX7 (Two-hybrid), LSM2 (Two-hybrid)

ESM2 similar proteins: A0A1L8G016, A1A5Q0, B3DH20, D3Z8X7, D4A1F2, E1BTG2, F1MF74, F1RA39, O14730, O60308, O88978, O94851, O95801, P51432, P70566, Q1RMR5, Q1RMT7, Q28FY0, Q2YDM7, Q3UHZ5, Q3UM18, Q4KLT3, Q4R3F0, Q4R8L2, Q5BJT6, Q5EA11, Q5ZJD3, Q6AZN0, Q6P5Q4, Q7Z569, Q80V31, Q863A4, Q863A5, Q863A6, Q863A7, Q86X45, Q8BML1, Q8CCP0, Q8R368, Q8R3H9

Diamond homologs: A0A1L8G016, B3DH20, B6CZ45, B6CZ54, O88978, Q1RMR5, Q28FY0, Q4R3F0, Q5EAD8, Q6FV04, Q86X45, Q9DAK8, Q9NJE9, Q9VR52, Q28CU0, Q32KP2, Q9D3R3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	34
Likely pathogenic	10
Uncertain significance	139
Likely benign	111
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071740	NM_012472.6(DNAAF11):c.450_451delinsGT (p.Ile150_Glu151delinsMetTer)	Pathogenic
1335719	NM_012472.6(DNAAF11):c.1168C>T (p.Arg390Ter)	Pathogenic
1526036	NM_012472.6(DNAAF11):c.1142del (p.Val381fs)	Pathogenic
1681037	NM_012472.6(DNAAF11):c.724_725del (p.Asn242fs)	Pathogenic
1799677	NM_012472.6(DNAAF11):c.738_745dup (p.Phe249fs)	Pathogenic
1800310	NM_012472.6(DNAAF11):c.1024C>T (p.Arg342Ter)	Pathogenic
1800373	NM_012472.6(DNAAF11):c.328C>T (p.Gln110Ter)	Pathogenic
208996	NM_012472.6(DNAAF11):c.630del (p.Trp210fs)	Pathogenic
2137422	NM_012472.6(DNAAF11):c.845del (p.Lys282fs)	Pathogenic
2149443	NM_012472.6(DNAAF11):c.974+1G>T	Pathogenic
2421581	NM_012472.6(DNAAF11):c.1A>G (p.Met1Val)	Pathogenic
2787661	NM_012472.6(DNAAF11):c.451G>T (p.Glu151Ter)	Pathogenic
2842606	NM_012472.6(DNAAF11):c.845dup (p.Lys283fs)	Pathogenic
2978634	NM_012472.6(DNAAF11):c.55_56del (p.Val19fs)	Pathogenic
3346952	NM_012472.6(DNAAF11):c.653+1G>A	Pathogenic
3631750	NM_012472.6(DNAAF11):c.64dup (p.Ser22fs)	Pathogenic
3654296	NM_012472.6(DNAAF11):c.302_309del (p.Gly101fs)	Pathogenic
3655793	NM_012472.6(DNAAF11):c.169_173delinsTCCCAAT (p.Gly57fs)	Pathogenic
3721556	NM_012472.6(DNAAF11):c.224T>G (p.Leu75Ter)	Pathogenic
3900047	Single allele	Pathogenic
39794	NM_012472.6(DNAAF11):c.598_599del (p.Lys200fs)	Pathogenic
39795	NM_012472.6(DNAAF11):c.574C>T (p.Gln192Ter)	Pathogenic
39796	NM_012472.6(DNAAF11):c.576dup (p.Glu193fs)	Pathogenic
4294413	NM_012472.6(DNAAF11):c.10+2T>C	Pathogenic
4713190	NM_012472.6(DNAAF11):c.940_941insGGCCGGTCGCGGTGGCTCACGCCTGTAATCACAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAGAAAGATAACG (p.Asn313_Glu314insGlyProValAlaValAlaHisAlaCysAsnHisSerThrLeuGlyGlyArgGlyGlyArgIleThrArgSerXaaXaaXaaLysLysLysLysLysLysLysLysAspAsn)	Pathogenic
4777357	NM_012472.6(DNAAF11):c.486T>G (p.Tyr162Ter)	Pathogenic
540325	NM_012472.6(DNAAF11):c.633C>A (p.Tyr211Ter)	Pathogenic
540328	NM_012472.6(DNAAF11):c.1050del (p.Gln351fs)	Pathogenic
652985	NM_012472.6(DNAAF11):c.10+1G>A	Pathogenic
654068	NM_012472.6(DNAAF11):c.936_937del (p.Asp312fs)	Pathogenic

SpliceAI

2571 predictions. Top by Δscore:

Variant	Effect	Δscore
8:132610161:CCTA:C	donor_loss	1.0000
8:132610162:CTAC:C	donor_loss	1.0000
8:132610163:TAC:T	donor_loss	1.0000
8:132610165:C:A	donor_loss	1.0000
8:132610257:AATGG:A	acceptor_gain	1.0000
8:132610258:ATGG:A	acceptor_gain	1.0000
8:132610259:TGG:T	acceptor_gain	1.0000
8:132610260:GG:G	acceptor_gain	1.0000
8:132610262:C:CC	acceptor_gain	1.0000
8:132610263:T:C	acceptor_loss	1.0000
8:132610268:A:C	acceptor_gain	1.0000
8:132611289:CTTA:C	donor_loss	1.0000
8:132611290:TTACC:T	donor_loss	1.0000
8:132611291:TA:T	donor_loss	1.0000
8:132611292:A:AC	donor_gain	1.0000
8:132611293:C:CC	donor_gain	1.0000
8:132611293:C:CG	donor_loss	1.0000
8:132611293:CCTTT:C	donor_gain	1.0000
8:132611361:TACCT:T	acceptor_loss	1.0000
8:132611362:ACC:A	acceptor_loss	1.0000
8:132611364:C:A	acceptor_loss	1.0000
8:132611365:T:A	acceptor_loss	1.0000
8:132611367:C:CT	acceptor_gain	1.0000
8:132612882:C:CT	donor_gain	1.0000
8:132622609:A:AC	donor_gain	1.0000
8:132622610:C:CC	donor_gain	1.0000
8:132622723:C:CT	acceptor_gain	1.0000
8:132622724:A:AC	acceptor_gain	1.0000
8:132622724:A:C	acceptor_gain	1.0000
8:132625267:AATAC:A	donor_loss	1.0000

AlphaMissense

3130 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:132638070:A:C	N98K	0.999
8:132638070:A:T	N98K	0.999
8:132637995:G:C	N123K	0.998
8:132637995:G:T	N123K	0.998
8:132656858:G:C	N76K	0.998
8:132656858:G:T	N76K	0.998
8:132661476:A:C	N54K	0.998
8:132661476:A:T	N54K	0.998
8:132638067:G:C	F99L	0.997
8:132638067:G:T	F99L	0.997
8:132638069:A:G	F99L	0.997
8:132638080:A:G	L95P	0.997
8:132638086:A:T	L93H	0.997
8:132656883:A:T	L68H	0.997
8:132638086:A:G	L93P	0.996
8:132656859:T:A	N76I	0.996
8:132661601:C:G	A13P	0.996
8:132637939:A:G	L142S	0.995
8:132638071:T:A	N98I	0.995
8:132661486:A:G	L51P	0.995
8:132638095:A:T	L90Q	0.994
8:132656870:A:C	N72K	0.994
8:132656870:A:T	N72K	0.994
8:132656874:A:G	L71S	0.994
8:132661492:A:G	L49P	0.994
8:132661492:A:T	L49H	0.994
8:132661501:A:G	L46S	0.994
8:132661509:G:C	C43W	0.994
8:132661600:G:T	A13D	0.994
8:132610217:A:C	S363R	0.993

dbSNP variants (sampled 300 via entrez): RS1000023225 (8:132693078 G>A), RS1000027323 (8:132651900 C>A), RS1000058574 (8:132595681 A>G), RS1000070609 (8:132621056 G>A,C), RS1000097229 (8:132628011 A>C), RS1000141688 (8:132602625 G>C), RS1000151675 (8:132622908 C>A,G), RS1000168202 (8:132579330 T>C), RS1000173232 (8:132696037 C>T), RS1000177585 (8:132635241 C>A,T), RS1000250491 (8:132693267 G>C), RS1000263074 (8:132646725 C>G), RS1000307810 (8:132628493 G>A), RS1000321220 (8:132598670 C>T), RS1000323130 (8:132645573 G>A,T)

Disease associations

OMIM: gene MIM:614930 | disease phenotypes: MIM:614935, MIM:244400, MIM:126200

GenCC curated gene-disease

Disease	Classification	Inheritance
primary ciliary dyskinesia 19	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
primary ciliary dyskinesia 19	Definitive	AR

Mondo (5): primary ciliary dyskinesia 19 (MONDO:0013979), primary ciliary dyskinesia (MONDO:0016575), primary ciliary dyskinesia 1 (MONDO:0009484), multiple sclerosis, susceptibility to (MONDO:0007462), infertility disorder (MONDO:0005047)

Orphanet (3): Primary ciliary dyskinesia (Orphanet:244), Situs ambiguus (Orphanet:157769), Primary ciliary dyskinesia, Kartagener type (Orphanet:98861)

HPO phenotypes

56 total (30 of 56 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:0004469	Chronic bronchitis
HP:0005301	Persistent left superior vena cava
HP:0005425	Recurrent sinopulmonary infections

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

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
D007619	Kartagener Syndrome	C08.127.384.500; C08.200.531; C08.695.501; C09.150.531; C14.240.400.280.500; C14.280.400.280.500; C16.131.077.245.500.531; C16.131.240.400.280.500; C16.131.740.501; C16.131.810.250.500; C16.320.184.500.531; C16.320.480

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	4
sodium arsenite	affects acetylation, affects methylation, decreases expression, increases expression	3
Benzo(a)pyrene	increases expression, increases methylation	2
afuresertib	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
trichostatin A	affects expression, decreases reaction	1
monomethylarsonous acid	affects acetylation, affects methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases reaction, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	increases expression, affects cotreatment	1
Nickel	affects expression, decreases reaction	1
Silicon Dioxide	increases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	decreases reaction, increases expression	1
Magnetite Nanoparticles	increases methylation	1

Clinical trials (associated diseases)

207 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
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
NCT06384976	PHASE2	ACTIVE_NOT_RECRUITING	KYSA-7: A Study of Anti-CD19 CAR T-Cell Therapy, in Subjects With Refractory Primary and Secondary Progressive Multiple Sclerosis
NCT06782724	PHASE2	RECRUITING	Psilocybin Therapy for Psychological Distress in Palliative Patients
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
NCT05102682	PHASE1	COMPLETED	Robotics for Mobility Rehabilitation in MS
NCT06999434	PHASE1	RECRUITING	Exploring the Utility of [18F]3F4AP for Demyelination Imaging
NCT04901715	EARLY_PHASE1	COMPLETED	Functional Studies of Novel Genes Mutated in Primary Ciliary Dyskinesia II: Genotype to Phenotype
NCT00005650	Not specified	COMPLETED	Genetic Study of Patients With Primary Ciliary Dyskinesia
NCT00323167	Not specified	COMPLETED	Rare Genetic Disorders of the Breathing Airways
NCT00368446	Not specified	COMPLETED	Genetic Disorders of Mucociliary Clearance in Nontuberculous Mycobacterial Lung Disease
NCT00450918	Not specified	COMPLETED	Evaluating Progression of and Diagnostic Tools for Primary Ciliary Dyskinesia in Children and Adolescents
NCT00608556	Not specified	COMPLETED	Dyskinesia, Heterotaxy and Congenital Heart Disease
NCT00686309	Not specified	UNKNOWN	Comparison of On-line and Off-line Measurements of Exhaled Nitric Oxide (NO)
NCT00722878	Not specified	COMPLETED	Long-term Lung Function and Disease Progression in Children With Early Onset Primary Ciliary Dyskinesia Lung Disease
NCT00739817	Not specified	UNKNOWN	Screening for Primary Ciliary Dyskinesia Using Nasal Nitric Oxide
NCT00783887	Not specified	COMPLETED	Diagnosis of Primary Ciliary Dyskinesia
NCT00807482	Not specified	RECRUITING	Pathogenesis of Primary Ciliary Dyskinesia (PCD) Lung Disease
NCT01070914	Not specified	UNKNOWN	Early Detection and Characterization of Primary Ciliary Dyskinesia
NCT01155115	Not specified	COMPLETED	Inflammatory and Microbiologic Markers in Sputum: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia
NCT01246258	Not specified	COMPLETED	Otolith Function in Patients With Primary Ciliary Dyskinesia