CFAP46

Summary

CFAP46 (cilia and flagella associated protein 46, HGNC:25247) is a protein-coding gene on chromosome 10q26.3, encoding Cilia- and flagella-associated protein 46 (Q8IYW2). As part of the central apparatus of the cilium axoneme plays a role in cilium movement.

Predicted to be involved in axoneme assembly. Predicted to be located in axoneme.

Source: NCBI Gene 54777 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary ciliary dyskinesia (Limited, ClinGen)
• GWAS associations: 2
• Clinical variants (ClinVar): 252 total — 3 pathogenic
• MANE Select transcript: NM_001200049

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25247
Approved symbol	CFAP46
Name	cilia and flagella associated protein 46
Location	10q26.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434A1721, bA288G11.4, bA288G11.5, bB137A17.2, FLJ25954, bB137A17.3
Ensembl gene	ENSG00000171811
Ensembl biotype	protein_coding
OMIM	618543
Entrez	54777

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 retained_intron, 4 protein_coding

ENST00000368585, ENST00000368586, ENST00000417862, ENST00000448925, ENST00000466834, ENST00000475340, ENST00000476633, ENST00000486104, ENST00000639072

RefSeq mRNA: 1 — MANE Select: NM_001200049 NM_001200049

CCDS: CCDS58101

Canonical transcript exons

ENST00000368586 — 58 exons

Exon	Start	End
ENSE00000728988	132810950	132811031
ENSE00000728992	132812785	132812897
ENSE00000728997	132814152	132814254
ENSE00000729000	132814577	132814612
ENSE00000729003	132814686	132814746
ENSE00000729004	132814844	132814914
ENSE00001254293	132934752	132934862
ENSE00001254302	132936961	132937055
ENSE00001254310	132937552	132937675
ENSE00001447479	132920059	132920182
ENSE00001447480	132922104	132922224
ENSE00001447481	132922480	132922708
ENSE00001447483	132869274	132869372
ENSE00001447484	132872676	132872824
ENSE00001447485	132876812	132876961
ENSE00001554512	132924696	132924886
ENSE00001593379	132850244	132850432
ENSE00001601764	132898959	132899121
ENSE00001622548	132885821	132885959
ENSE00001622628	132892333	132892417
ENSE00001629256	132877881	132878087
ENSE00001654851	132918393	132918520
ENSE00001658633	132885103	132885286
ENSE00001667660	132880861	132881032
ENSE00001669003	132879426	132879631
ENSE00001673665	132919315	132919442
ENSE00001684992	132836817	132836914
ENSE00001696028	132846057	132846227
ENSE00001711713	132851117	132851305
ENSE00001716036	132833358	132833525
ENSE00001726468	132926568	132926666
ENSE00001730340	132834654	132834775
ENSE00001745282	132867375	132867507
ENSE00001757440	132846932	132847111
ENSE00001780270	132834041	132834123
ENSE00001788223	132929705	132929804
ENSE00001792219	132847187	132847321
ENSE00001827089	132860782	132860982
ENSE00001862592	132860417	132860523
ENSE00001869666	132859071	132859247
ENSE00001877017	132866025	132866171
ENSE00001895056	132857590	132857788
ENSE00002215044	132942436	132942570
ENSE00003429698	132808392	132808904
ENSE00003455941	132810409	132810489
ENSE00003458895	132912655	132912820
ENSE00003475141	132909919	132910068
ENSE00003475783	132916549	132916682
ENSE00003496314	132899535	132899666
ENSE00003508622	132940996	132941060
ENSE00003517616	132941591	132941722
ENSE00003522123	132913046	132913258
ENSE00003526720	132941980	132942104
ENSE00003557641	132938589	132938753
ENSE00003571315	132836142	132836218
ENSE00003586297	132908468	132908634
ENSE00003602056	132909137	132909244
ENSE00003664654	132835304	132835434

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 98.44.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6879 / max 109.6137, expressed in 659 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112087	1.6879	659

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.44	gold quality
right testis	UBERON:0004534	93.73	gold quality
left testis	UBERON:0004533	93.40	gold quality
gastrocnemius	UBERON:0001388	90.60	gold quality
testis	UBERON:0000473	89.21	gold quality
muscle of leg	UBERON:0001383	88.49	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.67	gold quality
muscle organ	UBERON:0001630	84.00	gold quality
right frontal lobe	UBERON:0002810	83.65	gold quality
bronchial epithelial cell	CL:0002328	83.47	gold quality
epithelium of bronchus	UBERON:0002031	83.43	gold quality
bronchus	UBERON:0002185	82.11	gold quality
anterior cingulate cortex	UBERON:0009835	82.07	gold quality
cingulate cortex	UBERON:0003027	81.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.98	gold quality
left lobe of thyroid gland	UBERON:0001120	78.03	gold quality
right lobe of thyroid gland	UBERON:0001119	77.88	gold quality
ventricular zone	UBERON:0003053	77.09	gold quality
adenohypophysis	UBERON:0002196	77.01	gold quality
hypothalamus	UBERON:0001898	76.89	gold quality
caudate nucleus	UBERON:0001873	76.87	gold quality
nucleus accumbens	UBERON:0001882	76.81	gold quality
thyroid gland	UBERON:0002046	76.74	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	76.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.14	gold quality
prefrontal cortex	UBERON:0000451	75.13	gold quality
lower esophagus mucosa	UBERON:0035834	74.62	gold quality
amygdala	UBERON:0001876	74.39	gold quality
putamen	UBERON:0001874	73.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.69

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Hypermethylation of 5’-TTC40 gene might play a role in nasopharyngeal carcinoma development; nevertheless, other studies are needed. (PMID:25101295)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cfap46	ENSMUSG00000049571
rattus_norvegicus	Cfap46	ENSRNOG00000027374

Protein

Protein identifiers

Cilia- and flagella-associated protein 46 — Q8IYW2 (reviewed: Q8IYW2)

Alternative names: Tetratricopeptide repeat protein 40

All UniProt accessions (3): Q8IYW2, A0A1W2PQB9, H0Y845

UniProt curated annotations — full annotation on UniProt →

Function. As part of the central apparatus of the cilium axoneme plays a role in cilium movement.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme.

Similarity. Belongs to the CFAP46 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IYW2-1	1	yes
Q8IYW2-2	2
Q8IYW2-3	3

RefSeq proteins (1): NP_001186978* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR039586	CFAP46	Family
IPR057466	CFAP46_TPR	Repeat

Pfam: PF25439

UniProt features (37 total): repeat 13, sequence variant 7, region of interest 5, compositionally biased region 5, splice variant 4, coiled-coil region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q8IYW2 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ORGANELLE_ASSEMBLY, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_AXONEME_ASSEMBLY, GOCC_CYTOPLASMIC_REGION, GOCC_CILIUM, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_MICROTUBULE_CYTOSKELETON_ORGANIZATION, SRC_UP.V1_UP, CBX5_TARGET_GENES, RYBP_TARGET_GENES, ZFP91_TARGET_GENES

GO Biological Process (3): axoneme assembly (GO:0035082), cilium movement involved in cell motility (GO:0060294), cell projection organization (GO:0030030)

GO Molecular Function (0):

GO Cellular Component (5): axoneme (GO:0005930), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
microtubule bundle formation	1
cellular component assembly	1
cilium assembly	1
cilium movement	1
cell motility	1
cilium-dependent cell motility	1
cellular component organization	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

926 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP46	CXorf58	Q96LI9	573
CFAP46	C19orf81	C9J6K1	446
CFAP46	CFAP74	Q9C0B2	394
CFAP46	NBPF19	A0A087WUL8	391
CFAP46	CFAP54	Q96N23	382
CFAP46	AXDND1	Q5T1B0	370
CFAP46	CFAP221	Q4G0U5	367
CFAP46	ARMC3	Q5W041	353
CFAP46	CFAP73	A6NFT4	351
CFAP46	PDZD9	Q8IXQ8	344
CFAP46	SYCE1L	A8MT33	339
CFAP46	VWA3A	A6NCI4	336
CFAP46	COL20A1	Q9P218	327
CFAP46	CFAP119	A1A4V9	326
CFAP46	MSI2	Q96DH6	325

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CFAP46	GAPDHS	psi-mi:“MI:0914”(association)	0.530
CFAP46	H1-4	psi-mi:“MI:0915”(physical association)	0.400
CFAP46	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
CFAP46	HMGA1	psi-mi:“MI:0915”(physical association)	0.400
CFAP46	ACTA2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (14): ALDH1A3 (Affinity Capture-MS), DHPS (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), TSR3 (Affinity Capture-MS), CFAP46 (Affinity Capture-RNA), CFAP46 (Proximity Label-MS), CFAP46 (Proximity Label-MS), CFAP46 (Proximity Label-MS), CFAP46 (Affinity Capture-MS), CFAP46 (Affinity Capture-MS), CFAP46 (Cross-Linking-MS (XL-MS)), CFAP46 (Cross-Linking-MS (XL-MS)), CFAP46 (Cross-Linking-MS (XL-MS)), SMC2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1S4D1D3, A0A1W2PR95, A0A8I6ASZ5, A8WE67, D2K8N5, D3Z8X7, D3ZND0, E1C760, E7EXT2, F6Y9J3, F7AEX0, O08836, O60308, P27641, P54729, P78318, Q0P4W3, Q14CX7, Q15021, Q2QY04, Q2YD98, Q3ZC62, Q4V8E4, Q5EAU9, Q61249, Q68FJ0, Q6NY52, Q6PBQ2, Q6PGY6, Q6QI44, Q7ZXA8, Q80V31, Q86VS3, Q8BWZ3, Q8C6E0, Q8C9J3, Q8IYW2, Q8K2Z4, Q8LDQ4, Q8LNU5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	175
Likely benign	42
Benign	3

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
149102	GRCh38/hg38 10q26.2-26.3(chr10:127849717-133622588)x1	Pathogenic
2498475	GRCh37/hg19 10q26.12-26.3(chr10:122610933-135439810)x1	Pathogenic
563785	GRCh37/hg19 10q26.3(chr10:131949020-135427143)x1	Pathogenic

SpliceAI

12226 predictions. Top by Δscore:

Variant	Effect	Δscore
10:132810403:CCTTA:C	donor_loss	1.0000
10:132810404:CTTAC:C	donor_loss	1.0000
10:132810405:TTACC:T	donor_loss	1.0000
10:132810406:TACCT:T	donor_loss	1.0000
10:132810407:A:AG	donor_loss	1.0000
10:132810485:CAGAT:C	acceptor_gain	1.0000
10:132810487:GAT:G	acceptor_gain	1.0000
10:132810489:TC:T	acceptor_loss	1.0000
10:132810490:C:CA	acceptor_loss	1.0000
10:132810490:C:CC	acceptor_gain	1.0000
10:132810491:T:C	acceptor_loss	1.0000
10:132810580:CGCA:C	donor_gain	1.0000
10:132810583:A:AC	donor_gain	1.0000
10:132810583:ACTTT:A	donor_gain	1.0000
10:132810584:C:CC	donor_gain	1.0000
10:132810584:CTTT:C	donor_gain	1.0000
10:132810584:CTTTC:C	donor_gain	1.0000
10:132810587:T:TA	donor_gain	1.0000
10:132810588:C:A	donor_gain	1.0000
10:132812781:TCAC:T	donor_loss	1.0000
10:132812782:CACCT:C	donor_loss	1.0000
10:132812784:C:A	donor_loss	1.0000
10:132812894:CTGG:C	acceptor_gain	1.0000
10:132812895:TGG:T	acceptor_gain	1.0000
10:132812896:GG:G	acceptor_gain	1.0000
10:132812898:C:CC	acceptor_gain	1.0000
10:132812899:T:A	acceptor_loss	1.0000
10:132812901:C:CT	acceptor_gain	1.0000
10:132814169:T:TA	donor_gain	1.0000
10:132814170:C:A	donor_gain	1.0000

AlphaMissense

17686 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:132942005:A:T	V50D	0.997
10:132846225:G:C	S2090R	0.993
10:132846225:G:T	S2090R	0.993
10:132846227:T:G	S2090R	0.993
10:132876904:A:G	W1424R	0.993
10:132876904:A:T	W1424R	0.993
10:132814186:A:G	W2452R	0.992
10:132814186:A:T	W2452R	0.992
10:132924790:A:G	W388R	0.992
10:132924790:A:T	W388R	0.992
10:132941683:A:C	Y72D	0.992
10:132922138:A:C	F524L	0.991
10:132922138:A:T	F524L	0.991
10:132922140:A:G	F524L	0.991
10:132938660:G:C	S155R	0.991
10:132938660:G:T	S155R	0.991
10:132938662:T:G	S155R	0.991
10:132919432:A:G	W581R	0.990
10:132919432:A:T	W581R	0.990
10:132941651:A:C	F82L	0.990
10:132941651:A:T	F82L	0.990
10:132941653:A:G	F82L	0.990
10:132885855:C:G	A1137P	0.989
10:132941011:G:T	A119D	0.989
10:132941997:C:G	A53P	0.989
10:132812887:A:G	W2467R	0.988
10:132812887:A:T	W2467R	0.988
10:132847001:G:C	S2066R	0.988
10:132847001:G:T	S2066R	0.988
10:132847003:T:G	S2066R	0.988

dbSNP variants (sampled 300 via entrez): RS1000022934 (10:132903300 T>C), RS1000032104 (10:132869037 C>T), RS1000111609 (10:132906844 G>A), RS1000140335 (10:132885342 C>T), RS1000153228 (10:132938991 C>T), RS1000192282 (10:132873724 C>A), RS1000194507 (10:132880759 C>T), RS1000227519 (10:132884584 A>C,G), RS1000238626 (10:132861447 G>A,T), RS1000257330 (10:132879002 G>A,C), RS1000264379 (10:132831566 C>G), RS1000303450 (10:132911472 G>A), RS1000304620 (10:132943107 G>A), RS1000307285 (10:132817488 A>G), RS1000344080 (10:132889173 A>C)

Disease associations

OMIM: gene MIM:618543 | disease phenotypes:

GenCC curated gene-disease

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
primary ciliary dyskinesia	Limited	AR

Mondo (0):

Orphanet (1): Situs ambiguus (Orphanet:157769)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009307_6	Spatial memory	1.000000e-06
GCST010917_7	Proportion of activated microglia (midfrontal cortex)	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	5
Benzo(a)pyrene	affects methylation, increases methylation, increases mutagenesis	2
bisphenol A	affects cotreatment, decreases methylation	1
terbufos	increases methylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	affects methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
Fulvestrant	decreases methylation, affects cotreatment	1
Vorinostat	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Fonofos	increases methylation	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Methapyrilene	increases methylation	1
Methotrexate	increases expression	1
Parathion	increases methylation	1
Phthalic Acids	affects methylation	1
Smoke	increases abundance, increases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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