CLXN

Summary

CLXN (calaxin, HGNC:25678) is a protein-coding gene on chromosome 8q11.21, encoding Calaxin (Q9HAE3). Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule.

Predicted to enable calcium ion binding activity. Predicted to be involved in several processes, including cilium movement; outer dynein arm assembly; and regulation of flagellated sperm motility. Located in sperm flagellum. Implicated in primary ciliary dyskinesia.

Source: NCBI Gene 79645 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliary dyskinesia, primary, 53 (Strong, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 33 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 64
• MANE Select transcript: NM_024593

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25678
Approved symbol	CLXN
Name	calaxin
Location	8q11.21
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11767, ODAD5
Ensembl gene	ENSG00000034239
Ensembl biotype	protein_coding
OMIM	619564
Entrez	79645

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000262103, ENST00000433756, ENST00000519425, ENST00000521002, ENST00000521701, ENST00000521721, ENST00000522254, ENST00000523008, ENST00000523092, ENST00000872856, ENST00000872857, ENST00000872858, ENST00000945699

RefSeq mRNA: 4 — MANE Select: NM_024593 NM_001142857, NM_001363973, NM_001363974, NM_024593

CCDS: CCDS47853, CCDS6145

Canonical transcript exons

ENST00000262103 — 6 exons

Exon	Start	End
ENSE00000693493	48729720	48729871
ENSE00000693502	48731348	48731503
ENSE00001087766	48723391	48724801
ENSE00002113875	48735094	48735268
ENSE00003528939	48730540	48730644
ENSE00003672799	48729042	48729146

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 99.18.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5325 / max 137.2809, expressed in 358 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92997	1.5325	358

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.18	gold quality
bronchial epithelial cell	CL:0002328	97.76	gold quality
epithelium of bronchus	UBERON:0002031	97.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.77	gold quality
bronchus	UBERON:0002185	96.30	gold quality
right testis	UBERON:0004534	91.77	gold quality
left testis	UBERON:0004533	91.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.42	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.54	gold quality
testis	UBERON:0000473	87.73	gold quality
left uterine tube	UBERON:0001303	84.29	gold quality
endocervix	UBERON:0000458	84.10	gold quality
body of uterus	UBERON:0009853	83.98	gold quality
left ovary	UBERON:0002119	82.88	gold quality
nasal cavity epithelium	UBERON:0005384	81.99	gold quality
right lung	UBERON:0002167	81.52	gold quality
right ovary	UBERON:0002118	81.07	gold quality
epithelium of nasopharynx	UBERON:0001951	80.27	gold quality
caput epididymis	UBERON:0004358	80.20	gold quality
ventricular zone	UBERON:0003053	79.81	gold quality
ovary	UBERON:0000992	78.33	gold quality
ectocervix	UBERON:0012249	76.33	gold quality
nasal cavity mucosa	UBERON:0001826	76.10	gold quality
fallopian tube	UBERON:0003889	75.68	gold quality
stromal cell of endometrium	CL:0002255	75.58	gold quality
body of pancreas	UBERON:0001150	74.51	gold quality
sperm	CL:0000019	73.94	silver quality
skin of abdomen	UBERON:0001416	72.40	gold quality
tibia	UBERON:0000979	72.29	gold quality
male germ cell	CL:0000015	72.02	silver quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	63.10
E-HCAD-1	yes	28.47
E-MTAB-10287	yes	25.95
E-GEOD-130148	yes	11.15
E-MTAB-9388	yes	7.69
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

54 targeting CLXN, 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-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-7158-5P	99.25	67.95	796
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-6877-3P	98.98	65.83	560

Literature-anchored findings (GeneRIF, showing 1)

• Pathogenic variants in CLXN encoding the outer dynein arm docking-associated calcium-binding protein calaxin cause primary ciliary dyskinesia. (PMID:36727596)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	clxn	ENSDARG00000061377
mus_musculus	Clxn	ENSMUSG00000068617
rattus_norvegicus	Clxn	ENSRNOG00000050091
drosophila_melanogaster	CG7646	FBGN0036926
drosophila_melanogaster	CG5890	FBGN0039380
caenorhabditis_elegans	ncs-2	WBGENE00003564
caenorhabditis_elegans		WBGENE00015867

Paralogs (14): GUCA1A (ENSG00000048545), NCALD (ENSG00000104490), NCS1 (ENSG00000107130), RCVRN (ENSG00000109047), GUCA1B (ENSG00000112599), KCNIP3 (ENSG00000115041), HPCAL1 (ENSG00000115756), HPCAL4 (ENSG00000116983), KCNIP2 (ENSG00000120049), HPCA (ENSG00000121905), GUCA1C (ENSG00000138472), VSNL1 (ENSG00000163032), KCNIP1 (ENSG00000182132), KCNIP4 (ENSG00000185774)

Protein

Protein identifiers

Calaxin — Q9HAE3 (reviewed: Q9HAE3)

Alternative names: EF-hand calcium-binding domain-containing protein 1

All UniProt accessions (4): Q9HAE3, H0YBJ9, H0YC53, H9KVD9

UniProt curated annotations — full annotation on UniProt →

Function. Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule. Seems to regulate the assembly of both ODAs and their axonemal docking complex onto ciliary microtubules. Regulates ciliary and flagellar motility and is required for cilia-driven determination of body laterality.

Subunit / interactions. Component of the outer dynein arm-docking complex along with ODAD1, ODAD2, ODAD3 and ODAD4.

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

Tissue specificity. Strong expression in the respiratory epithelium. Expressed in the sperm.

Disease relevance. Ciliary dyskinesia, primary, 53 (CILD53) [MIM:620642] A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Some patients exhibit randomization of left-right body asymmetry and situs inversus. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD53 is an autosomal recessive form characterized by randomization of the left-right body asymmetry and respiratory symptoms. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HAE3-1	1	yes
Q9HAE3-2	2

RefSeq proteins (4): NP_001136329, NP_001350902, NP_001350903, NP_078869* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR028846	Recoverin	Family

Pfam: PF13499

UniProt features (23 total): binding site 14, domain 3, splice variant 2, sequence variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HAE3-F1	89.78	0.78

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 (14): 115; 117; 124; 158; 160; 162; 164; 169; 77; 79; 81; 83 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 225 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_AXONEMAL_DYNEIN_COMPLEX_ASSEMBLY, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, WTGAAAT_UNKNOWN, GOBP_REGULATION_OF_MICROTUBULE_BASED_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_OUTER_DYNEIN_ARM_ASSEMBLY, GOBP_ORGANELLE_ASSEMBLY, GOBP_MICROTUBULE_BUNDLE_FORMATION, MULLIGHAN_NPM1_SIGNATURE_3_DN

GO Biological Process (5): cilium movement (GO:0003341), regulation of cilium movement (GO:0003352), regulation of signal transduction (GO:0009966), outer dynein arm assembly (GO:0036158), regulation of flagellated sperm motility (GO:1901317)

GO Molecular Function (2): calcium ion binding (GO:0005509), metal ion binding (GO:0046872)

GO Cellular Component (7): cilium (GO:0005929), axoneme (GO:0005930), sperm flagellum (GO:0036126), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
microtubule-based movement	1
cilium movement	1
regulation of microtubule-based movement	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
axonemal dynein complex assembly	1
flagellated sperm motility	1
regulation of cilium movement involved in cell motility	1
regulation of reproductive process	1
metal ion binding	1
cation binding	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
9+2 motile cilium	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cilium	1

Protein interactions and networks

STRING

1642 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLXN	CFAP96	A7E2U8	595
CLXN	CFAP184	Q2M329	590
CLXN	RSPRY1	Q96DX4	576
CLXN	PIERCE1	Q5BN46	575
CLXN	CFAP90	A4QMS7	573
CLXN	ODAD4	Q96NG3	573
CLXN	EAF1	Q96JC9	563
CLXN	IQUB	Q8NA54	560
CLXN	GPATCH3	Q96I76	532
CLXN	ODAD2	Q5T2S8	519
CLXN	ZNRF2	Q8NHG8	498
CLXN	ARMC3	Q5W041	497
CLXN	ODAD3	A5D8V7	489
CLXN	EFHC2	Q5JST6	487
CLXN	CYLC2	Q14093	484
CLXN	METTL6	Q8TCB7	484

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CLXN	HERC2	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): SNX9 (Affinity Capture-MS), NEURL4 (Affinity Capture-MS), AKAP9 (Affinity Capture-MS), HERC2 (Affinity Capture-MS), PDE4DIP (Affinity Capture-MS), SCYL1 (Affinity Capture-MS), HDAC6 (Affinity Capture-MS), PACSIN2 (Affinity Capture-MS)

ESM2 similar proteins: A0PJX0, A1L1L6, A4IG32, B1A8Z2, B1H2N3, C7A278, D2HZB0, O88456, P04632, P06813, P07090, P22676, P47728, Q08331, Q0IIL1, Q17QE5, Q1RMX9, Q2HJF8, Q2KI69, Q32L26, Q32LU1, Q3T0E8, Q3ZBY3, Q4R518, Q5PPL2, Q5RDF9, Q5ZM73, Q6NVC5, Q6P6Q9, Q6P8Y1, Q6PHZ8, Q6PIL6, Q8BG51, Q8HYN7, Q8IXI2, Q8R426, Q8VCX5, Q8WWF8, Q99828, Q99MG9

Diamond homologs: A0JM59, A5PMR2, A5PN09, A6QNM7, A6ZY34, A7TGY3, A7Z056, A8HAL1, B1AY13, B1AY15, B1WBD7, B2GUX4, B3LGK1, B3VSB7, F1M625, F8VPZ3, M9PD06, O24454, O57429, O60139, O75604, O88623, P29105, P32571, P35125, P36608, P37235, P39944, P40818, P42325, P51784, P62068, P62069, P62166, P62167, P62168, P62748, P62749, Q01988, Q06AT0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	25
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
2664150	NM_024593.4(CLXN):c.117_129del (p.Glu40fs)	Pathogenic
2664148	NM_024593.4(CLXN):c.292C>T (p.Arg98Ter)	Likely pathogenic
2664149	NM_024593.4(CLXN):c.367G>T (p.Glu123Ter)	Likely pathogenic
4292941	NM_024593.4(CLXN):c.8del (p.Arg3fs)	Likely pathogenic

SpliceAI

1090 predictions. Top by Δscore:

Variant	Effect	Δscore
8:48729038:ATAC:A	donor_loss	1.0000
8:48729040:A:C	donor_loss	1.0000
8:48729041:C:CA	donor_loss	1.0000
8:48729142:TGATC:T	acceptor_gain	1.0000
8:48729143:GATC:G	acceptor_gain	1.0000
8:48729145:TC:T	acceptor_gain	1.0000
8:48729146:CC:C	acceptor_gain	1.0000
8:48729146:CCTAG:C	acceptor_loss	1.0000
8:48729147:C:CC	acceptor_gain	1.0000
8:48729147:CTA:C	acceptor_loss	1.0000
8:48729868:CAAT:C	acceptor_gain	1.0000
8:48729872:C:CC	acceptor_gain	1.0000
8:48729873:T:C	acceptor_gain	1.0000
8:48730539:CATTT:C	donor_gain	1.0000
8:48730645:C:CC	acceptor_gain	1.0000
8:48731454:C:CT	acceptor_gain	1.0000
8:48731454:C:T	acceptor_gain	1.0000
8:48731457:C:CT	acceptor_gain	1.0000
8:48731458:A:T	acceptor_gain	1.0000
8:48735092:A:AC	donor_gain	1.0000
8:48735093:C:CC	donor_gain	1.0000
8:48735093:CAATG:C	donor_gain	1.0000
8:48729144:ATC:A	acceptor_gain	0.9900
8:48729716:TTACC:T	donor_loss	0.9900
8:48729717:T:TG	donor_loss	0.9900
8:48729718:ACCA:A	donor_loss	0.9900
8:48729756:T:TA	donor_gain	0.9900
8:48729867:GCAAT:G	acceptor_gain	0.9900
8:48729868:CAATC:C	acceptor_gain	0.9900
8:48729869:AATC:A	acceptor_loss	0.9900

AlphaMissense

1429 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:48730594:A:G	W89R	0.999
8:48730594:A:T	W89R	0.999
8:48731401:C:G	R54P	0.999
8:48729059:A:G	C187R	0.998
8:48729064:C:T	G185E	0.998
8:48729867:G:C	C108W	0.998
8:48729052:G:T	P189H	0.997
8:48729057:A:C	C187W	0.997
8:48729065:C:G	G185R	0.997
8:48729065:C:T	G185R	0.997
8:48729730:A:G	L154P	0.997
8:48729742:A:T	V150D	0.997
8:48729832:A:T	I120N	0.997
8:48729864:A:C	F109L	0.997
8:48729864:A:T	F109L	0.997
8:48729866:A:G	F109L	0.997
8:48731479:A:G	L28P	0.997
8:48729055:A:G	L188P	0.996
8:48729805:A:G	L129S	0.996
8:48730566:C:G	R98P	0.996
8:48730640:G:C	F73L	0.996
8:48730640:G:T	F73L	0.996
8:48730642:A:G	F73L	0.996
8:48731354:C:G	D70H	0.996
8:48731392:A:G	L57P	0.996
8:48729097:A:T	V174E	0.995
8:48729146:C:G	D158H	0.995
8:48729745:A:G	L149S	0.995
8:48729868:C:T	C108Y	0.995
8:48730584:C:T	G92E	0.995

dbSNP variants (sampled 300 via entrez): RS1000005167 (8:48711328 T>C), RS1000013588 (8:48711986 A>G), RS1000116189 (8:48712642 C>A,G,T), RS1000343543 (8:48733693 C>A), RS1000520658 (8:48715760 C>T), RS1000526487 (8:48717532 A>G), RS1000637886 (8:48734400 C>T), RS1000715677 (8:48727813 A>C,G,T), RS1000897560 (8:48736379 A>G), RS1000990708 (8:48721166 C>G), RS1001011550 (8:48736795 TAAC>T), RS1001156301 (8:48716018 G>C), RS1001163572 (8:48710669 A>G), RS1001191990 (8:48718351 A>G), RS1001230878 (8:48712990 C>A)

Disease associations

OMIM: gene MIM:619564 | disease phenotypes: MIM:615966, MIM:620642

GenCC curated gene-disease

Disease	Classification	Inheritance
ciliary dyskinesia, primary, 53	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ciliary dyskinesia, primary, 53	Strong	AR

Mondo (2): severe combined immunodeficiency due to DNA-PKcs deficiency (MONDO:0014423), ciliary dyskinesia, primary, 53 (MONDO:0957991)

Orphanet (1): Severe combined immunodeficiency due to DNA-PKcs deficiency (Orphanet:317425)

HPO phenotypes

64 total (30 of 64 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:0001320	Cerebellar vermis hypoplasia
HP:0001627	Abnormal heart morphology
HP:0001640	Cardiomegaly
HP:0001655	Patent foramen ovale
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:0002092	Pulmonary arterial hypertension
HP:0002093	Respiratory insufficiency
HP:0002110	Bronchiectasis
HP:0002119	Ventriculomegaly
HP:0002198	Dilated fourth ventricle
HP:0002257	Chronic rhinitis
HP:0002566	Intestinal malrotation
HP:0002643	Neonatal respiratory distress

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001104_3	Sudden cardiac arrest	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004278	sudden cardiac arrest

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, affects cotreatment, increases expression	6
arsenite	increases methylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Smoke	increases abundance, increases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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