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 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): heterotaxy, visceral, 11, autosomal, with male infertility (Moderate, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 134 total — 4 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 13 tissues, sQTL in 4 (q < 0.05)
• Phenotypes (HPO): 13
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.71 (unconstrained)
• MANE Select transcript: NM_012337
• Notable: 134 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 8 — 4 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay

MANE Select: ENST00000368099

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 5: 1

ENST00000368099, ENST00000426543, ENST00000475911, ENST00000476696, ENST00000479861, ENST00000479940, ENST00000998844, ENST00001122343

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.

Highest expression (Bgee): uterine tube, bronchial epithelial cell, epithelium of bronchus, bronchus, olfactory segment of nasal mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CFAP45 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 13 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

17 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	3.2e-37	-1.04	1:159898076:A:G
Brain Cerebellar Hemisphere	sqtl	6.1e-13	-0.54	1:159902445:A:G
Brain Cerebellum	sqtl	3.1e-08	-0.50	1:159858956:G:A
Whole Blood	eqtl	2.4e-07	-0.15	1:159922298:G:A
Cells EBV-transformed lymphocytes	eqtl	3.4e-05	-0.53	1:159925169:C:A
Cells Cultured fibroblasts	eqtl	5.3e-05	+0.74	1:159920013:G:A
Spleen	eqtl	5.6e-04	+0.31	1:159927598:C:T
Vagina	eqtl	6.3e-04	+2.57	1:159921594:C:T
Nerve Tibial	eqtl	6.6e-04	-0.32	1:159925471:G:A
Uterus	sqtl	3.8e-03	-3.25	1:160188840:C:T
Brain Cerebellar Hemisphere	eqtl	9.6e-03	-0.26	1:159839478:T:A
Testis	eqtl	1.9e-02	-0.14	1:159872589:A:G
Esophagus Gastroesophageal Junction	eqtl	2.2e-02	-0.16	1:159919896:G:A
Adrenal Gland	eqtl	2.7e-02	+0.44	1:160532203:T:C
Skin Sun Exposed Lower leg	eqtl	3.7e-02	-0.09	1:160460679:T:G
Artery Coronary	eqtl	4.7e-02	+0.18	1:159925746:G:A
Brain Cortex	eqtl	4.9e-02	-0.38	1:159103935:G:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
15429	0.4679	130

Top tissues by expression

showing 100 of 284 tissues 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
ventricular zone	UBERON:0003053	70.05	gold quality
upper lobe of lung	UBERON:0008948	69.71	gold quality
skin of leg	UBERON:0001511	69.47	gold quality
bone marrow	UBERON:0002371	68.75	gold quality
upper arm skin	UBERON:0004263	68.66	gold quality
endocervix	UBERON:0000458	68.63	gold quality
kidney epithelium	UBERON:0004819	68.63	silver quality
skin of abdomen	UBERON:0001416	68.43	gold quality
right atrium auricular region	UBERON:0006631	68.24	gold quality
gingival epithelium	UBERON:0001949	68.09	gold quality
tongue squamous epithelium	UBERON:0006919	68.06	gold quality
metanephric glomerulus	UBERON:0004736	67.94	silver quality
cardiac atrium	UBERON:0002081	67.82	gold quality
gingiva	UBERON:0001828	67.76	gold quality
tibial artery	UBERON:0007610	67.75	gold quality
popliteal artery	UBERON:0002250	67.67	gold quality
zone of skin	UBERON:0000014	67.47	gold quality
cerebellar cortex	UBERON:0002129	67.17	gold quality
cartilage tissue	UBERON:0002418	67.07	gold quality
cerebellar hemisphere	UBERON:0002245	67.00	gold quality
cerebellum	UBERON:0002037	66.70	gold quality
tendon	UBERON:0000043	66.51	gold quality
metanephros	UBERON:0000081	66.19	gold quality
right hemisphere of cerebellum	UBERON:0014890	66.03	gold quality
oviduct epithelium	UBERON:0004804	65.91	gold quality
cortex of kidney	UBERON:0001225	65.88	gold quality
myocardium	UBERON:0002349	65.74	gold quality
aorta	UBERON:0000947	65.70	gold quality
subcutaneous adipose tissue	UBERON:0002190	65.59	gold quality
lung	UBERON:0002048	65.48	gold quality
periodontal ligament	UBERON:0008266	65.27	gold quality
secondary oocyte	CL:0000655	65.06	gold quality
endometrium	UBERON:0001295	64.94	gold quality
trachea	UBERON:0003126	64.68	gold quality
mucosa of stomach	UBERON:0001199	64.47	gold quality
nephron tubule	UBERON:0001231	64.46	gold quality
monocyte	CL:0000576	64.33	gold quality
adult mammalian kidney	UBERON:0000082	64.23	gold quality
trabecular bone tissue	UBERON:0002483	64.23	gold quality
leukocyte	CL:0000738	64.11	gold quality
mononuclear cell	CL:0000842	64.08	gold quality
hypothalamus	UBERON:0001898	63.86	gold quality
ascending aorta	UBERON:0001496	63.75	gold quality
islet of Langerhans	UBERON:0000006	63.43	gold quality
thoracic aorta	UBERON:0001515	63.17	gold quality
kidney	UBERON:0002113	63.15	gold quality
stromal cell of endometrium	CL:0002255	62.66	gold quality
tibial nerve	UBERON:0001323	62.14	gold quality
parotid gland	UBERON:0001831	62.12	gold quality
granulocyte	CL:0000094	62.00	gold quality
uterus	UBERON:0000995	61.89	gold quality
inferior olivary complex	UBERON:0002127	61.86	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	61.85	gold quality
amniotic fluid	UBERON:0000173	61.45	gold quality
metanephros cortex	UBERON:0010533	61.44	gold quality
heart	UBERON:0000948	61.38	gold quality
cardiac muscle of right atrium	UBERON:0003379	61.26	gold quality
amygdala	UBERON:0001876	61.20	gold quality
left ventricle myocardium	UBERON:0006566	61.09	gold quality
thymus	UBERON:0002370	61.04	gold quality
spleen	UBERON:0002106	60.99	gold quality
saphenous vein	UBERON:0007318	60.67	gold quality
anatomical system	UBERON:0000467	60.64	gold quality
caudate nucleus	UBERON:0001873	60.56	gold quality
material anatomical entity	UBERON:0000465	60.42	gold quality
female reproductive system	UBERON:0000474	60.42	gold quality
multicellular organism	UBERON:0000468	60.41	gold quality
bone marrow cell	CL:0002092	60.40	silver quality
placenta	UBERON:0001987	60.27	gold quality
epithelium of mammary gland	UBERON:0003244	60.19	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

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 73 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Fallopian tube	tissue	42.1	high
Choroid plexus	tissue	27.0
Testis	tissue	19.8	medium
Periaqueductal gray	tissue	16.3
Basal ganglia	tissue	8.7	not detected
Amygdala	tissue	7.8
Olfactory bulb	tissue	7.5
Septum	tissue	7.4
Hippocampal formation	tissue	7.3
Hypothalamus	tissue	6.9
Cerebellum	tissue	6.6	not detected
Cerebral cortex	tissue	6.4	not detected
Insular cortex	tissue	6.4
Retrosplenial and cingulate cortex	tissue	6.0
Retrosplenial cortex	tissue	6.0
Corpus callosum	tissue	5.9
Entorhinal cortex	tissue	5.9
Temporal cortex	tissue	5.9
Ventral forebrain	tissue	5.8
Prefrontal cortex	tissue	5.6
Pons	tissue	4.9
Occipital cortex	tissue	4.9
Motor cortex	tissue	4.7
Lung	tissue	4.7	not detected
Putamen	tissue	4.4
Medulla oblongata	tissue	4.4
Thalamus	tissue	4.4
Somatosensory cortex	tissue	4.2
Midbrain	tissue	3.8
Superior colliculi	tissue	3.2
Substantia nigra	tissue	3.2
Spinal cord	tissue	3.1
Locus coeruleus	tissue	2.0
Caudate putamen	tissue	2.0
Frontal cortex	tissue	1.9
Cervix	tissue	1.6	not detected
Endometrium 1	tissue	1.3	low
Nucleus accumbens	tissue	1.3
Bone marrow	tissue	0.8	not detected
Thyroid gland	tissue	0.6	not detected
Breast	tissue	0.5	not detected
Stomach 1	tissue	0.5	not detected
Urinary bladder	tissue	0.5	not detected
Spleen	tissue	0.5	not detected
Hippocampus	tissue	0.5	not detected
Pituitary gland	tissue	0.4
Heart muscle	tissue	0.4	not detected
Seminal vesicle	tissue	0.4	not detected
Vagina	tissue	0.3	not detected
Adipose tissue	tissue	0.3	not detected
Esophagus	tissue	0.3	not detected
Smooth muscle	tissue	0.3	not detected
Placenta	tissue	0.3	not detected
Appendix	tissue	0.3	not detected
Ovary	tissue	0.2	not detected
Gallbladder	tissue	0.2	not detected
Duodenum	tissue	0.2	not detected
Thymus	tissue	0.2
Tonsil	tissue	0.2	not detected
Skin 1	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 134; highest nTPM — Nucleus tractus solitarii (17.6), Periaquaductal grey, lateral (13.8), Cervical spinal cord, central gray (12.3), Periaquaductal grey, dorsal (10.5), Superior vestibular nucleus (9.5).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CFAP45 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

16 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1.07e-06, LOEUF 0.713, missense Z 0.659 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000368099 — one region, missense o/e 0.98.

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1919120) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 17 distinct phenotype terms.

Mouse phenotype (MP)	Records
domed cranium	1
abnormal liver morphology	1
dextrocardia	1
decreased body size	1
hydrocephaly	1
male infertility	1
premature death	1
asthenozoospermia	1
heterotaxia	1
right aortic arch	1
abnormal motile primary cilium physiology	1
decreased hyperactivated sperm motility	1
right-sided stomach	1
lung situs inversus	1
situs inversus totalis	1
abnormal azygos vein topology	1
left sided inferior vena cava	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Sus scrofa	A0A480NP79	89.3%	Diamond
Bos taurus	Q32LN4	89.3%	Diamond
Chlamydomonas reinhardtii	A8I9E8	39.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SNHG28	ncRNA	284677
VSIG8	protein-coding	391123
TAGLN2	protein-coding	8407
MIR4259	ncRNA	100422852
SLAMF8	protein-coding	56833
IGSF9	protein-coding	57549
FCRL6	protein-coding	343413
LINC01133	ncRNA	100505633
SLAMF9	protein-coding	89886
DUSP23	protein-coding	54935

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 (9 total): sequence variant 3, region of interest 2, chain 1, domain 1, coiled-coil region 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
7UNG	48-nm repeat of the human respiratory doublet microtubule	ELECTRON MICROSCOPY	3.6
8J07	96nm repeat of human respiratory doublet microtubule and associated axonemal complexes	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes, Congenital malformations, Other congenital malformations

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): end piece; mid piece; nucleoplasm; principal piece; basal body; cytosol

Antibody reliability (HPA): IH enhanced · IF uncertain

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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 (2): flagellated sperm motility (GO:0030317), establishment of left/right asymmetry (GO:0061966)

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

GO Cellular Component (13): nucleus (GO:0005634), axonemal microtubule (GO:0005879), cilium (GO:0005929), axoneme (GO:0005930), sperm flagellum (GO:0036126), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), sperm end piece (GO:0097229), 9+0 motile cilium (GO:0097728), 9+2 motile cilium (GO:0097729), axonemal B tubule inner sheath (GO:0160112), motile cilium (GO:0031514), polymeric cytoskeletal fiber (GO:0099513)

GO top-level categories

30 GO namespaces:

Category	Terms
cellular anatomical structure	5
sperm flagellum	3
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
determination of left/right symmetry	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
cilium	1
supramolecular fiber	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
establishment of left/right asymmetry	BP	mutant phenotype
flagellated sperm motility	BP	mutant phenotype
9+2 motile cilium	CC	direct assay
axonemal microtubule	CC	direct assay
axoneme	CC	direct assay
cilium	CC	direct assay
sperm end piece	CC	direct assay
sperm flagellum	CC	direct assay
sperm midpiece	CC	direct assay
sperm principal piece	CC	direct assay
AMP binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,538 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP45	CFAP52	Q8N1V2	721
CFAP45	DDX51	Q8N8A6	586
CFAP45	PACRG	Q96M98	539
CFAP45	TEKT1	Q969V4	539
CFAP45	CFAP126	Q5VTH2	530
CFAP45	EFHC1	Q5JVL4	526
CFAP45	DRC7	Q8IY82	523
CFAP45	CFAP20	Q9Y6A4	503
CFAP45	DAW1	Q8N136	503
CFAP45	ENKUR	Q8TC29	502
CFAP45	DNAI2	Q9GZS0	496
CFAP45	RSPH3	Q86UC2	491
CFAP45	DRC2	Q8IXS2	490
CFAP45	SPAG6	O75602	471
CFAP45	RSPH9	Q9H1X1	469

IntAct

Human interaction partners of CFAP45 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
ENKUR	physical association	0.560	3
GLS	physical association	0.400	2

BioGRID (18 interactions; top human partners by supporting records): GLS (Affinity Capture-MS; 2 records), CAPRIN1 (Cross-Linking-MS (XL-MS)), ELAVL1 (Affinity Capture-RNA), ENKUR (Two-hybrid), GAPDH (Cross-Linking-MS (XL-MS)), H2AFX (Affinity Capture-MS), KRT8 (Cross-Linking-MS (XL-MS)), MECP2 (Affinity Capture-MS), MYH9 (Cross-Linking-MS (XL-MS)), OBSL1 (Affinity Capture-MS), OLA1 (Cross-Linking-MS (XL-MS)), PARP9 (Proximity Label-MS), SAR1B (Affinity Capture-MS), TAGLN2 (Cross-Linking-MS (XL-MS)), TIPARP (Proximity Label-MS)

Disease & clinical

Genetic variants

Variant evidence for CFAP45: 134 ClinVar records (5 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	108
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (5)

Showing all 5 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1319990	NM_012337.3(CFAP45):c.1472_1477delinsT (p.Gln491fs)	Pathogenic	criteria provided, single submitter	2
4850564	NM_012337.3(CFAP45):c.1048C>T (p.Arg350Ter)	Likely pathogenic	criteria provided, single submitter	1
1319987	NM_012337.3(CFAP45):c.721C>T (p.Gln241Ter)	Pathogenic	no assertion criteria provided	1
1319988	NM_012337.3(CFAP45):c.907C>T (p.Arg303Ter)	Pathogenic	no assertion criteria provided	1
1319989	NM_012337.3(CFAP45):c.452_464del (p.Gln151fs)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CFAP45’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 1,314):

Position(s)	Effect	Δscore	Sites
1:159872948	donor_gain	1.0000
1:159873169	acceptor_gain	1.0000
1:159873169–159873170	acceptor_loss	1.0000	5
1:159876577	donor_gain	1.0000
1:159877347–159877348	donor_loss	1.0000	5
1:159877463–159877464	acceptor_loss	1.0000	4
1:159880701–159880702	acceptor_loss	1.0000	6
1:159880706	acceptor_gain	1.0000
1:159884434–159884435	donor_loss	1.0000	5
1:159884567	acceptor_gain	1.0000

AlphaMissense

515 missense substitutions predicted likely pathogenic (of 3,670 scored), across 242 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F446	7	0.830	0.971
C203	7	0.827	0.948
F39	7	0.823	0.948
W402	7	0.799	0.903
D381	7	0.770	0.884
D208	7	0.748	0.811
D35	7	0.664	0.759
Q210	6	0.812	0.955
E213	6	0.756	0.861
D387	6	0.725	0.753
F343	5	0.896	0.963
Y534	5	0.872	0.909
R393	5	0.858	0.990
K365	5	0.836	0.919
R400	5	0.824	0.929
M232	5	0.776	0.867
K431	5	0.745	0.936
K202	5	0.737	0.910
V34	5	0.724	0.809
D85	5	0.658	0.667

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Uterine Corpus Endometrial Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	unfavorable	6.49e-05
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	favorable	0.000224

Disease associations

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

GenCC curated gene-disease

1 curated gene-disease records:

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

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
Fetal anomalies	green
Laterality disorders and isomerism	green

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

HPO phenotypes

13 phenotypes (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:

Study	Trait	p-value
GCST000730_8	Bilirubin levels	2e-10
GCST008103_86	Bipolar disorder	3e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004570	bilirubin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

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 abundance, increases expression	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)

Via MONDO — disease-level, not drug-specific.