CFAP45

Summary

CFAP45 (cilia and flagella associated protein 45, HGNC:17229) is a protein-coding gene on chromosome 1q23.2, encoding Cilia- and flagella-associated protein 45 (Q9UL16). Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.

Enables AMP binding activity. Involved in establishment of left/right asymmetry and flagellated sperm motility. Located in axonemal microtubule and sperm flagellum. Implicated in visceral heterotaxy 11.

Source: NCBI Gene 25790 — RefSeq curated summary.

At a glance

• Gene–disease (curated): heterotaxy, visceral, 11, autosomal, with male infertility (Moderate, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 131 total — 4 pathogenic
• Phenotypes (HPO): 13
• MANE Select transcript: NM_012337

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17229
Approved symbol	CFAP45
Name	cilia and flagella associated protein 45
Location	1q23.2
Locus type	gene with protein product
Status	Approved
Aliases	NESG1
Ensembl gene	ENSG00000213085
Ensembl biotype	protein_coding
OMIM	605152
Entrez	25790

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000368099, ENST00000426543, ENST00000475911, ENST00000476696, ENST00000479861, ENST00000479940

RefSeq mRNA: 1 — MANE Select: NM_012337 NM_012337

CCDS: CCDS30914

Canonical transcript exons

ENST00000368099 — 12 exons

Exon	Start	End
ENSE00001446315	159876556	159876749
ENSE00001866409	159900096	159900165
ENSE00003477298	159890480	159890622
ENSE00003482372	159872364	159872563
ENSE00003500238	159872944	159873168
ENSE00003549103	159880554	159880700
ENSE00003567836	159893180	159893305
ENSE00003577220	159877349	159877462
ENSE00003660849	159888352	159888496
ENSE00003723803	159886511	159886689
ENSE00003732236	159884436	159884565
ENSE00003741076	159887841	159888011

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 98.57.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4679 / max 46.9128, expressed in 130 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15429	0.4679	130

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.57	gold quality
bronchial epithelial cell	CL:0002328	96.38	gold quality
epithelium of bronchus	UBERON:0002031	96.23	gold quality
bronchus	UBERON:0002185	95.21	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.20	gold quality
sperm	CL:0000019	90.52	gold quality
left testis	UBERON:0004533	89.69	gold quality
right testis	UBERON:0004534	89.10	gold quality
male germ cell	CL:0000015	88.28	gold quality
epithelium of nasopharynx	UBERON:0001951	86.84	gold quality
testis	UBERON:0000473	86.53	gold quality
mucosa of paranasal sinus	UBERON:0005030	85.94	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.38	gold quality
nasal cavity epithelium	UBERON:0005384	82.59	gold quality
choroid plexus epithelium	UBERON:0003911	80.70	gold quality
nasal cavity mucosa	UBERON:0001826	79.33	gold quality
sural nerve	UBERON:0015488	78.98	gold quality
right lung	UBERON:0002167	77.60	gold quality
blood	UBERON:0000178	76.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.37	gold quality
fallopian tube	UBERON:0003889	74.40	gold quality
calcaneal tendon	UBERON:0003701	73.79	gold quality
caput epididymis	UBERON:0004358	73.53	gold quality
triceps brachii	UBERON:0001509	72.75	gold quality
diaphragm	UBERON:0001103	71.87	gold quality
upper lobe of left lung	UBERON:0008952	71.86	gold quality
left uterine tube	UBERON:0001303	71.69	gold quality
renal glomerulus	UBERON:0000074	71.55	silver quality
gluteal muscle	UBERON:0002000	71.40	gold quality
hair follicle	UBERON:0002073	70.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	62.89
E-MTAB-10287	yes	26.39
E-GEOD-130148	yes	10.98
E-ANND-3	yes	10.20
E-MTAB-9388	yes	7.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting CFAP45, 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-6721-5P	99.93	68.92	2981
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-8078	98.32	65.73	361
HSA-MIR-503-5P	97.87	66.83	575
HSA-MIR-376A-2-5P	96.43	68.06	715

Literature-anchored findings (GeneRIF, showing 8)

• Decreased expression of NESG1 is associated with nasopharyngeal carcinoma. (PMID:20715168)
• Decreased NESG1 expression is an unfavorable prognostic factor for nasopharyngeal carcinoma. (PMID:22140479)
• Used proteomics technology to globally examine NESG1-controlled proteins in nasopharyngeal carcinoma(NPC) cells. Interestingly, a-enolase (ENO1), an overexpressed gene in NPC, was confirmed as a NESG1-regulated protein in NPC cells. (PMID:22997098)
• Down-regulated CCDC19 expression was observed in non-small cell lung cancers. (PMID:24976536)
• this study identified a novel mechanism that MAGI2-AS3/miR-15b-5p/CCDC19 signaling pathway regulates bladder cancer progression. (PMID:30442369)
• CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module. (PMID:33139725)
• VPS33B interacts with NESG1 to suppress cell growth and cisplatin chemoresistance in ovarian cancer. (PMID:33788346)
• The cilia and flagella associated protein CFAP52 orchestrated with CFAP45 is required for sperm motility in mice. (PMID:37236356)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cfap45	ENSDARG00000068103
mus_musculus	Cfap45	ENSMUSG00000026546
rattus_norvegicus	Cfap45	ENSRNOG00000008492
drosophila_melanogaster	CG11449	FBGN0037162

Protein

Protein identifiers

Cilia- and flagella-associated protein 45 — Q9UL16 (reviewed: Q9UL16)

Alternative names: Coiled-coil domain-containing protein 19, Nasopharyngeal epithelium-specific protein 1

All UniProt accessions (3): A0A087WUV1, A0A087X182, Q9UL16

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating. It is an AMP-binding protein that may facilitate dynein ATPase-dependent ciliary and flagellar beating via adenine nucleotide homeostasis. May function as a donor of AMP to AK8 and hence promote ADP production.

Subunit / interactions. Microtubule inner protein component of sperm flagellar doublet microtubules. Interacts with AK8; dimerization with AK8 may create a cavity at the interface of the dimer that can accommodate AMP. Interacts with CFAP52. Interacts with ENKUR. Directly interacts with DNALI1. Interacts with DNAH11. Interacts with DNAI1.

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

Tissue specificity. Expressed in respiratory cells and in sperm (at protein level). Expressed in nasopharyngeal epithelium and trachea.

Disease relevance. Heterotaxy, visceral, 11, autosomal, with male infertility (HTX11) [MIM:619608] A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can be associated with a variety of congenital defects including cardiac malformations. HTX11 is an autosomal recessive form associated with male infertility due to reduced flagellar motility. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CFAP45 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UL16-1	1	yes
Q9UL16-2	2

RefSeq proteins (1): NP_036469* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033253	CFAP45	Family
IPR043597	TPH_dom	Domain

Pfam: PF13868

UniProt features (8 total): sequence variant 3, region of interest 2, chain 1, coiled-coil region 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7UNG	ELECTRON MICROSCOPY	3.6
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UL16-F1	77.03	0.29

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 149 (showing top): GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, RIZKI_TUMOR_INVASIVENESS_3D_DN, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_SPECIFICATION_OF_SYMMETRY, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_MOVEMENT, GOBP_REGULATION_OF_MICROTUBULE_BASED_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_REGULATION_OF_CILIUM_MOVEMENT, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM, GOCC_SPERM_PRINCIPAL_PIECE, GOCC_SPERM_MIDPIECE, GOCC_CYTOPLASMIC_MICROTUBULE, GOCC_CILIUM

GO Biological Process (5): flagellated sperm motility (GO:0030317), epithelial cilium movement involved in determination of left/right asymmetry (GO:0060287), regulation of cilium beat frequency involved in ciliary motility (GO:0060296), establishment of left/right asymmetry (GO:0061966), cerebrospinal fluid circulation (GO:0090660)

GO Molecular Function (2): AMP binding (GO:0016208), protein binding (GO:0005515)

GO Cellular Component (14): extracellular region (GO:0005576), nucleus (GO:0005634), axonemal microtubule (GO:0005879), cilium (GO:0005929), axoneme (GO:0005930), sperm flagellum (GO:0036126), 9+0 motile cilium (GO:0097728), 9+2 motile cilium (GO:0097729), axonemal B tubule inner sheath (GO:0160112), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), motile cilium (GO:0031514), cell projection (GO:0042995), polymeric cytoskeletal fiber (GO:0099513)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
epithelial cilium movement involved in extracellular fluid movement	2
determination of left/right symmetry	2
cytoskeleton	2
motile cilium	2
inner dynein arm	2
outer dynein arm	2
axonemal doublet microtubule	2
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
regulation of cilium beat frequency	1
regulation of cilium movement involved in cell motility	1
regulation of biological quality	1
nervous system process	1
adenyl ribonucleotide binding	1
anion binding	1
cation binding	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasmic microtubule	1
axoneme	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
microtubule	1
ciliary plasm	1
9+2 motile cilium	1
radial spoke	1
axonemal central pair	1
A axonemal microtubule	1
axonemal microtubule doublet inner sheath	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cilium	1
supramolecular fiber	1

Protein interactions and networks

STRING

2720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP45	VPS33B	Q9H267	793
CFAP45	DDX51	Q8N8A6	600
CFAP45	CFAP52	Q8N1V2	597
CFAP45	DRC7	Q8IY82	558
CFAP45	MCTP1	Q6DN14	499
CFAP45	DAW1	Q8N136	495
CFAP45	DNAH10	Q8IVF4	477
CFAP45	C7orf57	Q8NEG2	476
CFAP45	DNAH7	Q8WXX0	460
CFAP45	TMEM202	A6NGA9	457
CFAP45	DRC2	Q8IXS2	449
CFAP45	LRRC23	Q53EV4	449
CFAP45	CLUH	O75153	445
CFAP45	ZER1	Q7Z7L7	444
CFAP45	CCDC8	Q9H0W5	443

IntAct

7 interactions, top by confidence:

A	B	Type	Score
ENKUR	CFAP45	psi-mi:“MI:0915”(physical association)	0.560
CFAP45	GLS	psi-mi:“MI:0915”(physical association)	0.400
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
CFAP45	GLS	psi-mi:“MI:0914”(association)	0.350
CFAP45	ENKUR	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): CFAP45 (Co-fractionation), GLS (Affinity Capture-MS), CFAP45 (Two-hybrid), CFAP45 (Affinity Capture-MS), GLS (Affinity Capture-MS), SAR1B (Affinity Capture-MS), CFAP45 (Affinity Capture-MS), CFAP45 (Cross-Linking-MS (XL-MS)), CFAP45 (Cross-Linking-MS (XL-MS)), CFAP45 (Affinity Capture-MS), CFAP45 (Cross-Linking-MS (XL-MS)), CFAP45 (Cross-Linking-MS (XL-MS)), CFAP45 (Cross-Linking-MS (XL-MS)), CFAP45 (Cross-Linking-MS (XL-MS)), CFAP45 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IFG5, A0A480NP79, A0A974E306, A0AUT1, A0JLY1, A4IJ21, A5A6J4, A8I9E8, A8IRJ7, A8IUG5, E1BJL9, F1N7G5, M0R3K6, M1V4Y8, O95990, Q0VC09, Q0VFZ6, Q17QH9, Q1RM03, Q2KI00, Q2KIQ2, Q32LH1, Q3TGF2, Q3TVW5, Q4R698, Q4R7T8, Q4R8Y5, Q5NVP3, Q5RE49, Q5U4F3, Q5XIN9, Q61884, Q6AXN9, Q6AXQ8, Q6AYL4, Q6PBA8, Q6ZN84, Q78TU8, Q8BRC6, Q8N443

Diamond homologs: A0A480NP79, A8I9E8, Q32LN4, Q9D9U9, Q9UL16

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	107
Likely benign	10
Benign	1

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1319987	NM_012337.3(CFAP45):c.721C>T (p.Gln241Ter)	Pathogenic
1319988	NM_012337.3(CFAP45):c.907C>T (p.Arg303Ter)	Pathogenic
1319989	NM_012337.3(CFAP45):c.452_464del (p.Gln151fs)	Pathogenic
1319990	NM_012337.3(CFAP45):c.1472_1477delinsT (p.Gln491fs)	Pathogenic

SpliceAI

2175 predictions. Top by Δscore:

Variant	Effect	Δscore
1:159872948:G:C	donor_gain	1.0000
1:159872963:T:A	donor_gain	1.0000
1:159873164:GAGCC:G	acceptor_gain	1.0000
1:159873165:AGCC:A	acceptor_gain	1.0000
1:159873166:GCC:G	acceptor_gain	1.0000
1:159873166:GCCCT:G	acceptor_gain	1.0000
1:159873167:CC:C	acceptor_gain	1.0000
1:159873167:CCC:C	acceptor_gain	1.0000
1:159873168:CC:C	acceptor_gain	1.0000
1:159873169:C:CC	acceptor_gain	1.0000
1:159873169:C:T	acceptor_gain	1.0000
1:159876576:AT:A	donor_gain	1.0000
1:159876576:ATC:A	donor_gain	1.0000
1:159876577:T:C	donor_gain	1.0000
1:159877344:GGTAC:G	donor_loss	1.0000
1:159877345:GTAC:G	donor_loss	1.0000
1:159877346:TA:T	donor_loss	1.0000
1:159877347:ACCTG:A	donor_loss	1.0000
1:159877463:C:T	acceptor_loss	1.0000
1:159880553:CCAT:C	donor_gain	1.0000
1:159880562:T:TA	donor_gain	1.0000
1:159880696:ATGTC:A	acceptor_gain	1.0000
1:159880697:TGTC:T	acceptor_gain	1.0000
1:159880699:TC:T	acceptor_gain	1.0000
1:159880700:CC:C	acceptor_gain	1.0000
1:159880701:C:CC	acceptor_gain	1.0000
1:159880706:A:T	acceptor_gain	1.0000
1:159884430:TGTTA:T	donor_loss	1.0000
1:159884431:GTTAC:G	donor_loss	1.0000
1:159884432:TTA:T	donor_loss	1.0000

AlphaMissense

3670 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:159876730:C:G	R393P	0.990
1:159877357:C:G	A384P	0.990
1:159876737:C:G	A391P	0.989
1:159886658:C:G	R207P	0.989
1:159886677:C:G	A201P	0.988
1:159876700:C:G	R403P	0.987
1:159886653:C:G	A209P	0.987
1:159886665:C:G	A205P	0.986
1:159887891:C:G	A180P	0.984
1:159886571:C:G	R236P	0.983
1:159876580:C:G	R443P	0.981
1:159873098:C:G	A475P	0.980
1:159876731:G:T	R393S	0.979
1:159872947:A:G	L525P	0.977
1:159873088:A:G	L478P	0.974
1:159873085:C:G	R479P	0.972
1:159876739:C:G	R390P	0.972
1:159876746:C:G	A388P	0.972
1:159876570:G:C	F446L	0.971
1:159876570:G:T	F446L	0.971
1:159876572:A:G	F446L	0.971
1:159877453:C:G	A352P	0.967
1:159887995:C:G	R145P	0.967
1:159876602:C:G	A436P	0.966
1:159876701:G:T	R403S	0.963
1:159880569:A:C	F343L	0.963
1:159880569:A:T	F343L	0.963
1:159880571:A:G	F343L	0.963
1:159890489:C:G	R88P	0.963
1:159873043:C:G	R493P	0.962

dbSNP variants (sampled 300 via entrez): RS1000004436 (1:159896640 A>C,G), RS1000107619 (1:159874515 A>AG), RS1000324876 (1:159894041 A>G), RS1000344421 (1:159878176 T>A), RS1000607023 (1:159895161 C>A), RS1000677217 (1:159893774 T>C), RS1000743300 (1:159901477 T>C), RS1000779159 (1:159877913 T>G), RS1000804132 (1:159883098 A>C), RS1001035133 (1:159889068 A>G), RS1001061250 (1:159895503 T>C,G), RS1001127699 (1:159898993 C>G), RS1001270598 (1:159892099 G>A,C), RS1001286825 (1:159872740 C>A), RS1001629660 (1:159892065 T>A,C)

Disease associations

OMIM: gene MIM:605152 | disease phenotypes: MIM:619608

GenCC curated gene-disease

Disease	Classification	Inheritance
heterotaxy, visceral, 11, autosomal, with male infertility	Moderate	Autosomal recessive

Mondo (1): heterotaxy, visceral, 11, autosomal, with male infertility (MONDO:0030475)

Orphanet (0):

HPO phenotypes

13 total (13 of 13 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000389	Chronic otitis media
HP:0001696	Situs inversus totalis
HP:0001748	Polysplenia
HP:0002247	Duodenal atresia
HP:0002566	Intestinal malrotation
HP:0003577	Congenital onset
HP:0010445	Primum atrial septal defect
HP:0011109	Chronic sinusitis
HP:0011577	Partial atrioventricular canal defect
HP:0031590	Asthenopia
HP:0033036	Decreased nasal nitric oxide
HP:0034011	Reduced progressive sperm motility

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000730_8	Bilirubin levels	2.000000e-10
GCST008103_100	Bipolar disorder	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004570	bilirubin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	3
Estradiol	affects cotreatment, increases expression, decreases expression	2
Smoke	increases abundance, increases expression	2
Valproic Acid	increases expression, increases methylation	2
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
ferrous chloride	increases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
di-n-butylphosphoric acid	affects expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Coal	increases expression, increases abundance	1
Diethylstilbestrol	decreases expression	1
Lead	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Isotretinoin	decreases expression	1
Aflatoxin B1	increases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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