CFAP52

Summary

CFAP52 (cilia and flagella associated protein 52, HGNC:16053) is a protein-coding gene on chromosome 17p13.1, encoding Cilia- and flagella-associated protein 52 (Q8N1V2). Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme.

WD repeat-containing proteins, such as WDR16, play crucial roles in a wide range of physiologic functions, including signal transduction, RNA processing, remodeling the cytoskeleton, regulation of vesicular traffic, and cell division (Silva et al., 2005 [PubMed 15967112]).

Source: NCBI Gene 146845 — RefSeq curated summary.

At a glance

• Gene–disease (curated): situs inversus (Supportive, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 178 total — 1 pathogenic, 5 likely-pathogenic
• GTEx eGene: eQTL in 6 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 9
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.02 (unconstrained)
• MANE Select transcript: NM_145054
• Notable: 178 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16053
Approved symbol	CFAP52
Name	cilia and flagella associated protein 52
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	WDRPUH, FLJ37528
Ensembl gene	ENSG00000166596
Ensembl biotype	protein_coding
OMIM	609804
Entrez	146845

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 4 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000352665

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2, TSL 3: 3, TSL 4: 3, TSL 5: 1

ENST00000352665, ENST00000396219, ENST00000572333, ENST00000574097, ENST00000574937, ENST00000575247, ENST00000576320, ENST00000576499, ENST00000576630, ENST00000576714, ENST00001102652, ENST00001136942

RefSeq mRNA: 2 — MANE Select: NM_145054 NM_001080556, NM_145054

CCDS: CCDS11149, CCDS42262

Canonical transcript exons

ENST00000352665 — 14 exons

Exon	Start	End
ENSE00001860783	9643023	9643447
ENSE00002673831	9576642	9576765
ENSE00003465907	9635405	9635556
ENSE00003487230	9638609	9638711
ENSE00003512498	9628672	9628820
ENSE00003541818	9594193	9594321
ENSE00003564959	9586698	9586834
ENSE00003586515	9632888	9633033
ENSE00003613159	9600067	9600183
ENSE00003623403	9608119	9608219
ENSE00003663167	9598234	9598333
ENSE00003673535	9641724	9641835
ENSE00003690418	9612309	9612479
ENSE00003708106	9585773	9585972

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 99.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5138 / max 61.0039, expressed in 120 samples.

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

Genetic regulation across tissues (GTEx eQTL / sQTL)

CFAP52 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

7 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	1.1e-03	+1.83	17:9636563:T:C
Liver	eqtl	2.7e-03	+0.46	17:9691997:A:G
Testis	eqtl	2.7e-03	+0.15	17:9564139:G:T
Artery Aorta	eqtl	9.4e-03	-0.25	17:9195973:T:C
Breast Mammary Tissue	eqtl	1.6e-02	+0.26	17:9775737:C:G
Lung	eqtl	2.9e-02	+0.08	17:8724181:C:A
Thyroid	eqtl	5.0e-02	+0.55	17:9832303:A:G

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
159544	0.3061	84
159545	0.2077	72

Top tissues by expression

showing 100 of 253 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.36	gold quality
right uterine tube	UBERON:0001302	98.67	gold quality
bronchus	UBERON:0002185	98.57	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.74	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.93	gold quality
oviduct epithelium	UBERON:0004804	88.30	gold quality
fallopian tube	UBERON:0003889	87.24	gold quality
nasal cavity epithelium	UBERON:0005384	85.35	gold quality
epithelium of nasopharynx	UBERON:0001951	85.24	gold quality
sperm	CL:0000019	84.71	gold quality
endothelial cell	CL:0000115	83.51	gold quality
caput epididymis	UBERON:0004358	82.15	gold quality
left testis	UBERON:0004533	81.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.94	gold quality
right testis	UBERON:0004534	80.77	gold quality
middle temporal gyrus	UBERON:0002771	80.52	gold quality
testis	UBERON:0000473	79.39	gold quality
trachea	UBERON:0003126	78.78	gold quality
adult organism	UBERON:0007023	77.55	gold quality
nasal cavity mucosa	UBERON:0001826	75.74	gold quality
right lung	UBERON:0002167	75.74	gold quality
Brodmann (1909) area 23	UBERON:0013554	74.12	gold quality
adenohypophysis	UBERON:0002196	71.40	gold quality
prefrontal cortex	UBERON:0000451	71.20	gold quality
pituitary gland	UBERON:0000007	71.11	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.86	gold quality
buccal mucosa cell	CL:0002336	70.54	gold quality
left uterine tube	UBERON:0001303	70.29	gold quality
right frontal lobe	UBERON:0002810	70.05	gold quality
anterior cingulate cortex	UBERON:0009835	69.99	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	69.77	gold quality
hypothalamus	UBERON:0001898	69.66	gold quality
frontal cortex	UBERON:0001870	69.15	gold quality
neocortex	UBERON:0001950	68.57	gold quality
superior vestibular nucleus	UBERON:0007227	68.26	gold quality
Ammon’s horn	UBERON:0001954	68.15	gold quality
cerebral cortex	UBERON:0000956	67.93	gold quality
caudate nucleus	UBERON:0001873	67.47	gold quality
endometrium	UBERON:0001295	66.77	gold quality
forebrain	UBERON:0001890	66.39	gold quality
ventricular zone	UBERON:0003053	66.25	gold quality
corpus callosum	UBERON:0002336	66.20	gold quality
amygdala	UBERON:0001876	65.88	gold quality
primary visual cortex	UBERON:0002436	65.63	gold quality
superior frontal gyrus	UBERON:0002661	65.25	gold quality
mucosa of transverse colon	UBERON:0004991	65.02	gold quality
temporal lobe	UBERON:0001871	64.27	gold quality
nucleus accumbens	UBERON:0001882	64.20	gold quality
metanephros cortex	UBERON:0010533	63.42	gold quality
cerebellar vermis	UBERON:0004720	63.16	gold quality
brain	UBERON:0000955	63.00	gold quality
lung	UBERON:0002048	62.87	gold quality
upper lobe of left lung	UBERON:0008952	62.55	gold quality
pancreatic ductal cell	CL:0002079	62.47	silver quality
endocervix	UBERON:0000458	62.37	gold quality
entorhinal cortex	UBERON:0002728	62.32	silver quality
upper lobe of lung	UBERON:0008948	61.93	gold quality
right lobe of liver	UBERON:0001114	61.07	gold quality
postcentral gyrus	UBERON:0002581	60.65	silver quality
islet of Langerhans	UBERON:0000006	60.46	gold quality
tendon of biceps brachii	UBERON:0008188	60.16	gold quality
occipital lobe	UBERON:0002021	60.06	gold quality
rectum	UBERON:0001052	60.05	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	59.82	gold quality
left lobe of thyroid gland	UBERON:0001120	58.69	gold quality
myocardium	UBERON:0002349	58.63	gold quality
body of pancreas	UBERON:0001150	58.61	gold quality
spinal cord	UBERON:0002240	58.38	gold quality
mucosa of stomach	UBERON:0001199	58.19	gold quality
thyroid gland	UBERON:0002046	58.10	gold quality
transverse colon	UBERON:0001157	58.03	gold quality
pancreas	UBERON:0001264	57.87	gold quality
parietal lobe	UBERON:0001872	57.59	silver quality
substantia nigra	UBERON:0002038	57.23	gold quality
uterus	UBERON:0000995	57.07	gold quality
metanephros	UBERON:0000081	56.50	gold quality
right lobe of thyroid gland	UBERON:0001119	56.40	gold quality
calcaneal tendon	UBERON:0003701	56.38	gold quality
medulla oblongata	UBERON:0001896	56.37	gold quality
tendon	UBERON:0000043	56.27	gold quality
tibialis anterior	UBERON:0001385	55.95	silver quality
adult mammalian kidney	UBERON:0000082	55.75	gold quality
medial globus pallidus	UBERON:0002477	55.75	gold quality
prostate gland	UBERON:0002367	55.52	gold quality
midbrain	UBERON:0001891	55.50	gold quality
lower esophagus mucosa	UBERON:0035834	55.17	gold quality
putamen	UBERON:0001874	54.99	gold quality
epithelial cell of pancreas	CL:0000083	54.95	gold quality
esophagus mucosa	UBERON:0002469	54.37	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
lower lobe of lung	UBERON:0008949	54.15	silver quality
kidney epithelium	UBERON:0004819	53.93	gold quality
uterine cervix	UBERON:0000002	53.74	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
female reproductive system	UBERON:0000474	53.41	gold quality
quadriceps femoris	UBERON:0001377	53.12	gold quality
deltoid	UBERON:0001476	53.07	gold quality
right adrenal gland	UBERON:0001233	53.05	gold quality
minor salivary gland	UBERON:0001830	53.02	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	60.78
E-MTAB-9388	yes	6.76
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 63 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Fallopian tube	tissue	54.4	high
Choroid plexus	tissue	37.0
Periaqueductal gray	tissue	23.6
Testis	tissue	11.4	medium
Basal ganglia	tissue	8.3	not detected
Hypothalamus	tissue	8.2
Septum	tissue	7.9
Pons	tissue	7.6
Hippocampal formation	tissue	7.5
Cerebral cortex	tissue	6.2	not detected
Somatosensory cortex	tissue	6.2
Thalamus	tissue	6.1
Occipital cortex	tissue	5.6
Amygdala	tissue	4.2
Midbrain	tissue	4.2
Lung	tissue	4.1	not detected
Medulla oblongata	tissue	4.0
Putamen	tissue	3.9
Superior colliculi	tissue	3.9
Temporal cortex	tissue	3.9
Entorhinal cortex	tissue	3.5
Locus coeruleus	tissue	3.4
Ventral forebrain	tissue	3.4
Prefrontal cortex	tissue	3.3
Retrosplenial and cingulate cortex	tissue	3.3
Motor cortex	tissue	3.2
Pituitary gland	tissue	3.1
Nucleus accumbens	tissue	2.9
Retrosplenial cortex	tissue	2.9
Caudate putamen	tissue	2.8
Insular cortex	tissue	2.8
Substantia nigra	tissue	2.7
Retina	tissue	2.2
Corpus callosum	tissue	2.2
Olfactory bulb	tissue	2.1
Spinal cord	tissue	2.0
Postcentral gyrus	tissue	2.0
Cerebellum	tissue	1.4	not detected
Hippocampus	tissue	1.3	not detected
Salivary gland	tissue	1.2	not detected
Cervix	tissue	1.1	not detected
Endometrium 1	tissue	1.0	medium
Small intestine	tissue	0.7	not detected
Frontal cortex	tissue	0.6
Duodenum	tissue	0.6	not detected
Thyroid gland	tissue	0.5	not detected
Parathyroid gland	tissue	0.3	not detected
Adrenal gland	tissue	0.3	not detected
Skin 1	tissue	0.2	not detected
Tongue	tissue	0.2
Gallbladder	tissue	0.2	not detected
Prostate	tissue	0.2	not detected
Thymus	tissue	0.2
Stomach 1	tissue	0.1	not detected
Ovary	tissue	0.1	not detected
Vagina	tissue	0.1	not detected
Seminal vesicle	tissue	0.1	not detected
Colon	tissue	0.1	not detected
Epididymis	tissue	0.1	not detected
Placenta	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Periaquaductal grey, lateral (26.9), Nucleus tractus solitarii (21.0), Cervical spinal cord, central gray (19.2), Superior vestibular nucleus (15.6), Periaquaductal grey, dorsal (15.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CFAP52 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-3163	100.00	77.23	8605
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-5007-5P	97.95	64.71	614
HSA-MIR-4264	96.35	64.76	1480
HSA-MIR-4653-3P	96.26	67.03	725

Functional genomics

gnomAD constraint: pLI 3.43e-15, LOEUF 1.02, missense Z 0.629 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000352665 — one region, missense o/e 1.00.

Literature-anchored findings (GeneRIF, showing 2)

• WDRPUH is a novel WD-repeat-containing protein highly expressed in human hepatocellular carcinoma and involved in cell proliferation (PMID:15967112)
• 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	cfap52	ENSDARG00000101679
mus_musculus	Cfap52	ENSMUSG00000020904
rattus_norvegicus	Cfap52	ENSRNOG00000037718
drosophila_melanogaster	CG10064	FBGN0035724

Paralogs (9): EML1 (ENSG00000066629), EML2 (ENSG00000125746), EML4 (ENSG00000143924), EML3 (ENSG00000149499), CFAP251 (ENSG00000158023), WDR90 (ENSG00000161996), EML5 (ENSG00000165521), CFAP44 (ENSG00000206530), EML6 (ENSG00000214595)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1919110) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 7 distinct phenotype terms.

Mouse phenotype (MP)	Records
hydrocephaly	1
male infertility	1
premature death	1
asthenozoospermia	1
abnormal sperm flagellum morphology	1
abnormal sperm mitochondrial sheath morphology	1
decreased sperm progressive motility	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
Bos taurus	E1BKF9	93.1%	Diamond
Sus scrofa	F1SS88	93.1%	Diamond
Macaca fascicularis	Q95JL5	89.4%	Diamond
Saccharomyces cerevisiae S288C	Q04491	86.4%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CSZ5	86.4%	Diamond
Neurospora crassa OR74A	Q9C270	56.8%	Diamond
Chlamydomonas reinhardtii	A8ILK1	44.6%	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
USP43	protein-coding	124739
NTN1	protein-coding	9423
STX8	protein-coding	9482
HUPCOS	ncRNA	124903925
DHRS7C	protein-coding	201140
GSG1L2	protein-coding	644070
GLP2R	protein-coding	9340
PIK3R5-DT	ncRNA	101928235
PIK3R5	protein-coding	23533

Protein

Protein identifiers

Cilia- and flagella-associated protein 52 — Q8N1V2 (reviewed: Q8N1V2)

Alternative names: WD repeat-containing protein 16, WD40-repeat protein up-regulated in HCC

All UniProt accessions (6): Q8N1V2, A0A096LNH3, I3L237, I3L2G9, K7ERC0, V9GY13

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme. Important for proper ciliary and flagellar beating. May act in cooperation with CFAP45 and axonemal dynein subunit DNAH11. May play a role in cell growth and/or survival.

Subunit / interactions. Microtubule inner protein component of sperm flagellar doublet microtubules. Interacts with BRCA2. Interacts with the CCT chaperonin complex. Interacts with HSP70. Interacts with AK8. Interacts with CFAP45. Interacts with DNAI1. Interacts with IQDC.

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

Tissue specificity. Expressed in respiratory cells and sperm (at protein level). Highly expressed in testis. Up-regulated in hepatocellular carcinoma (HCC).

Disease relevance. Heterotaxy, visceral, 10, autosomal, with male infertility (HTX10) [MIM:619607] 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. HTX10 is an autosomal recessive form associated with male infertility. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be a good candidate as a diagnostic marker for HCC as well as a potential molecular target for development of novel therapeutic drugs.

Similarity. Belongs to the CFAP52 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N1V2-1	1	yes
Q8N1V2-2	2
Q8N1V2-3	3

RefSeq proteins (2): NP_001074025, NP_659491* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR050630	WD_repeat_EMAP	Family

Pfam: PF00400

UniProt features (19 total): repeat 11, sequence conflict 3, splice variant 2, sequence variant 2, chain 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-Q8N1V2-F1	93.59	0.90

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): microtubules; basal body; centriolar satellite; primary cilium

Antibody reliability (HPA): IH enhanced · IF approved

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: 115 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_MALE_GAMETE_GENERATION, GOBP_SPECIFICATION_OF_SYMMETRY, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, RFX1_02, GOBP_FERTILIZATION, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM, 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 (1): protein binding (GO:0005515)

GO Cellular Component (7): axonemal microtubule (GO:0005879), axoneme (GO:0005930), sperm flagellum (GO:0036126), sperm midpiece (GO:0097225), 9+2 motile cilium (GO:0097729), axonemal B tubule inner sheath (GO:0160112), cytoplasm (GO:0005737)

GO top-level categories

22 GO namespaces:

Category	Terms
cellular anatomical structure	4
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
determination of left/right symmetry	1
binding	1
cytoplasmic microtubule	1
axoneme	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
9+2 motile cilium	1
sperm flagellum	1
radial spoke	1
motile cilium	1
inner dynein arm	1
outer dynein arm	1
axonemal central pair	1
axonemal doublet microtubule	1
A axonemal microtubule	1
axonemal microtubule doublet inner sheath	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 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	mutant phenotype
axonemal microtubule	CC	direct assay
axoneme	CC	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 1,608 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP52	CCT4	P50991	830
CFAP52	CFAP45	Q9UL16	721
CFAP52	TCP1	P17987	685
CFAP52	DRC2	Q8IXS2	624
CFAP52	CFAP126	Q5VTH2	618
CFAP52	PACRG	Q96M98	606
CFAP52	SPATC1L	Q9H0A9	594
CFAP52	CFAP53	Q96M91	594
CFAP52	ENKUR	Q8TC29	593
CFAP52	SPAG6	O75602	582
CFAP52	DNALI1	O14645	577
CFAP52	CFAP20	Q9Y6A4	571
CFAP52	SAXO2	Q658L1	569
CFAP52	EFHC1	Q5JVL4	554
CFAP52	RIBC1	Q8N443	540

IntAct

Human interaction partners of CFAP52 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
ASMTL	association	0.530	2
NUDC	physical association	0.400	1
NUDCD2	physical association	0.400	1
NUDCD3	physical association	0.400	1

BioGRID (14 interactions; top human partners by supporting records): ASMTL (Affinity Capture-MS; 2 records), CRYZL1 (Affinity Capture-MS; 2 records), STIP1 (Affinity Capture-MS; 2 records), BRCA2 (Affinity Capture-Western), CCT4 (Affinity Capture-Western), CCT6A (Affinity Capture-MS), CLTCL1 (Affinity Capture-MS), ETAA1 (Synthetic Lethality), HSPA4 (Affinity Capture-Western), HSPA8 (Affinity Capture-MS), TCP1 (Affinity Capture-Western)

Disease & clinical

Genetic variants

Variant evidence for CFAP52: 178 ClinVar records (6 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	5
Uncertain significance	108
Likely benign	24
Benign	15

Top pathogenic / likely-pathogenic (6)

Showing all 6 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
1443577	NM_145054.5(CFAP52):c.536+1G>T	Likely pathogenic	criteria provided, single submitter	1
2503114	NM_145054.5(CFAP52):c.705del (p.Thr236fs)	Likely pathogenic	criteria provided, single submitter	1
3065385	NM_145054.5(CFAP52):c.547C>T (p.Arg183Ter)	Likely pathogenic	criteria provided, single submitter	1
4540415	NM_145054.5(CFAP52):c.1219C>T (p.Arg407Ter)	Likely pathogenic	criteria provided, single submitter	1
625821	GRCh37/hg19 17p13.1(chr17:9489128-9489263)	Likely pathogenic	criteria provided, single submitter	1
1319991	NC_000017.10:g.9481617_9489649del	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CFAP52’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 1,411):

Position(s)	Effect	Δscore	Sites
17:9594319	donor_gain	1.0000
17:9598231	acceptor_gain	1.0000
17:9612306	acceptor_gain	1.0000
17:9612480–9612481	donor_loss	1.0000	5
17:9628821–9628822	donor_loss	1.0000	4
17:9576766–9576767	donor_loss	0.9900	5
17:9594172	acceptor_gain	0.9900
17:9598229	acceptor_gain	0.9900
17:9598232–9598233	acceptor_loss	0.9900	5
17:9598334–9598335	donor_loss	0.9900	6

AlphaMissense

1,498 missense substitutions predicted likely pathogenic (of 4,099 scored), across 413 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
D134	8	0.976	0.991
H110	8	0.966	0.994
H586	8	0.965	0.989
D482	8	0.963	0.992
H460	8	0.960	0.981
H63	8	0.931	0.971
F505	8	0.924	0.986
F174	8	0.913	0.993
H416	8	0.909	0.964
D395	8	0.902	0.971
D133	8	0.900	0.967
D228	8	0.892	0.961
F348	8	0.873	0.985
F119	8	0.854	0.985
D566	8	0.832	0.963
D608	8	0.804	0.940
W614	7	0.996	0.999
W572	7	0.992	0.999
W359	7	0.991	0.998
W96	7	0.988	0.998

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme)

Disease associations

OMIM: gene MIM:609804 | disease phenotypes: MIM:619607

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
situs inversus	Supportive	Autosomal dominant
visceral heterotaxy	Limited	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 (3): heterotaxy, visceral, 10, autosomal, with male infertility (MONDO:0030474), situs inversus (MONDO:0010029), visceral heterotaxy (MONDO:0018677)

Orphanet (1): Situs inversus totalis (Orphanet:101063)

HPO phenotypes

9 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000403	Recurrent otitis media
HP:0001651	Dextrocardia
HP:0001696	Situs inversus totalis
HP:0003251	Male infertility
HP:0003363	Abdominal situs inversus
HP:0011109	Chronic sinusitis
HP:0012735	Cough
HP:0033036	Decreased nasal nitric oxide

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D012857	Situs Inversus	C16.131.810

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	2
methyleugenol	decreases expression	1
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Cisplatin	increases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Methapyrilene	increases methylation	1
Rotenone	decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

showing 60 of 137 trials:

NCT	Phase	Status	Title
NCT02202382	Phase 4	COMPLETED	Effects of Korean Red Ginseng on Male Infertility
NCT02204826	Phase 4	COMPLETED	Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study
NCT03802864	Phase 4	COMPLETED	Post-operative Pain Control of Testicular Sperm Extraction Using Liposomal Bupivacaine
NCT06100432	Phase 4	ACTIVE_NOT_RECRUITING	Effect of Eurycoma Longifolia (DLBS5055) and Multivitamins (Vitamin C+Vitamin E+ β-carotene) for Infertile Males
NCT07523022	Phase 4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
NCT00975117	Phase 3	COMPLETED	Spermotrend in the Treatment of Male Infertility
NCT01407432	Phase 3	COMPLETED	Impact of Folates in the Care of the Male Infertility
NCT01895816	Phase 3	COMPLETED	Herbal Tonic Fertile Supplement(ZO2C5)
NCT02605070	Phase 3	TERMINATED	Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
NCT07402759	Phase 3	ACTIVE_NOT_RECRUITING	Impact of tdrd9 Gene Mutations in the Therapeutic Response to L-carnitine in Oligoasthenozoospermic Men
NCT01880086	Phase 2	COMPLETED	Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
NCT02061384	Phase 2	COMPLETED	RA-2 13-cis Retinoic Acid (Isotretinoin)
NCT02421887	Phase 2	COMPLETED	Males, Antioxidants, and Infertility Trial
NCT05200663	Phase 2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
NCT05290558	Phase 2	ACTIVE_NOT_RECRUITING	The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial
NCT06091969	Phase 2	NOT_YET_RECRUITING	Supplementation for Male Subfertility
NCT01595308	Phase 1	COMPLETED	A Pilot Study to Evaluate the Effect of Pomegranate Juice on Semen Parameters in Healthy Male Volunteers
NCT02122211	Phase 1	COMPLETED	Choline Dehydrogenase and Sperm Function: Effects of Betaine
NCT02575924	Phase 1	UNKNOWN	Influence of Culture Media on Clinical Outcomes in Poor Responders or Severe Male Infertility
NCT01591928	Not specified	COMPLETED	Heterotaxy Syndrome and Intestinal Rotation Abnormalities - A Prospective Study
NCT01929967	Not specified	COMPLETED	Defining Immunodeficiency in Heterotaxy Syndrome: Pilot Study Data
NCT02432079	Not specified	RECRUITING	Molecular Genetics of Heterotaxy and Related Congenital Heart Defects
NCT00608556	Not specified	COMPLETED	Dyskinesia, Heterotaxy and Congenital Heart Disease
NCT01304927	Phase 2/3	COMPLETED	Vitamin D Supplementation and Male Infertility: The CBG-study a Randomized Clinical Trial
NCT02349945	Phase 2/3	COMPLETED	FSH Receptor Polymorphism p.N680S and Efficacy of FSH Therapy
NCT05222841	Phase 2/3	COMPLETED	The Effectiveness of Spermotrend Food Supplement in the Treatment of Male Infertility
NCT05616598	Phase 2/3	COMPLETED	Effect of New Oral Treatment for Hepatitis C Virus on Seminal Parameters
NCT07669402	Phase 2/3	COMPLETED	Comparative Evaluation of the Efficacy of Letrozole, L-Carnitine, and Their Combination on Sperm Quality, Oxidative Stress, and ART Outcomes in Men With Idiopathic Oligoasthenoteratozoospermia.
NCT02025270	Phase 1/2	COMPLETED	MSCs For Treatment of Azoospermic Patients
NCT04541459	Early Phase 1	UNKNOWN	Validation of New Devices Against Ambient Electromagnetic Radiation
NCT05792813	Early Phase 1	UNKNOWN	Efficacy and Safety of Linggui Yangyuan Paste in Patients With Male Infertility
NCT06188936	Early Phase 1	COMPLETED	Home Semen Analysis Tests As a Screening Tool for Fertility Patients
NCT00012480	Not specified	COMPLETED	Effect of Environmental Exposures on the Egg Fertilizing Ability of Human Sperm
NCT00044369	Not specified	COMPLETED	Role of the Toxic Metal Cadmium in the Mechanism Producing Infertility With a Varicocele
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists
NCT00178516	Not specified	COMPLETED	Vitamin E and Male Infertility
NCT00315029	Not specified	COMPLETED	Patient-Centered Implementation Trial for Single Embryo Transfer
NCT00341120	Not specified	COMPLETED	Genetic Causes of Male Infertility
NCT00481403	Not specified	COMPLETED	Study of Sperm Molecular Factors Implicated in Male Fertility
NCT00548977	Not specified	COMPLETED	Genetic Studies Spermatogenic Failure
NCT00596739	Not specified	COMPLETED	A Study of the Pre- and Post-operative Semen Analyses and Reproductive Hormone Levels of Men Undergoing Weight-reduction Surgery
NCT00756561	Not specified	COMPLETED	HOP-2A - Intratesticular Hormone Levels
NCT00961558	Not specified	TERMINATED	Canadian Varicocelectomy Initiative (CVI): Effects on Male Fertility and Testicular Function of Varicocelectomy
NCT01075334	Not specified	UNKNOWN	Is a Carnitine Based Food Supplement (PorimoreTM) for Infertile Men Superior to Folate and Zinc With Regard to Pregnancy Rates in Intrauterine Insemination Cycles?
NCT01178463	Not specified	UNKNOWN	Spermatogonial Stem Cells in Azoospermic Patients: a Comparison Between Obstructive and Non-obstructive Azoospermia
NCT01232465	Not specified	COMPLETED	Impact of Sperm DNA Integrity on In Vitro Cycles
NCT01255397	Not specified	UNKNOWN	Proposed Research Protocol For Male Infertility
NCT01346631	Not specified	WITHDRAWN	The Paleolithic Diet and Male Factor Infertility
NCT01407484	Not specified	COMPLETED	Male Infertility Related With Post Infection Inflammatory Syndrome
NCT01856361	Not specified	TERMINATED	Ramipril for the Treatment of Oligospermia
NCT01859520	Not specified	COMPLETED	Swim up and Gradient Methods Used in Assisted Reproduction Techniques on DNA Fragmentation of Spermatozoa
NCT01974947	Not specified	COMPLETED	Metabolic Syndrome and Male Infertility
NCT02006446	Not specified	COMPLETED	Relationship Between Sperm Head Vacuoles and Sperm DNA Alterations in Infertile Men
NCT02062229	Not specified	UNKNOWN	Oxidative Stress and Lipidomics in Male Infertility
NCT02107521	Not specified	TERMINATED	IMSI in Couples With Previous Implantation Failures
NCT02166567	Not specified	COMPLETED	Effect of Sorting of Apoptotic Spermatozoa on the Outcome of Assisted Reproduction
NCT02268123	Not specified	COMPLETED	Correlating In Vitro Fertilization Outcomes After Euploid Blastocyst Transfer With Sperm DNA Fragmentation
NCT02272439	Not specified	COMPLETED	Endocrine Disrupting Chemicals: Potential Effects on Male and Female Reproductive Health in Saskatchewan
NCT02756923	Not specified	COMPLETED	Regulation of Stem Spermatogonia in the Mature Testis
NCT02839447	Not specified	WITHDRAWN	A Clinical Evaluation of Semen Quality Using the MiOXSYS™ System 2.0