CFAP206

Summary

CFAP206 (cilia and flagella associated protein 206, HGNC:21405) is a protein-coding gene on chromosome 6q15, encoding Cilia- and flagella-associated protein 206 (Q8IYR0). Essential for sperm motility and is involved in the regulation of the beating frequency of motile cilia on the epithelial cells of the respiratory tract.

Predicted to be involved in regulation of cilium beat frequency; regulation of flagellated sperm motility; and sperm axoneme assembly. Predicted to be located in A axonemal microtubule and motile cilium. Predicted to be part of radial spoke. Predicted to be active in axoneme and ciliary basal body.

Source: NCBI Gene 154313 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 97 total — 2 pathogenic
• Phenotypes (HPO): 9
• MANE Select transcript: NM_001031743

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21405
Approved symbol	CFAP206
Name	cilia and flagella associated protein 206
Location	6q15
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25974, dJ382I10.1
Ensembl gene	ENSG00000272514
Ensembl biotype	protein_coding
Entrez	154313

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000296885, ENST00000369562, ENST00000480123, ENST00000489338, ENST00000906987, ENST00000906988, ENST00000906989, ENST00000918053, ENST00000963802, ENST00000963803, ENST00000963804

RefSeq mRNA: 1 — MANE Select: NM_001031743 NM_001031743

CCDS: CCDS34498

Canonical transcript exons

ENST00000369562 — 13 exons

Exon	Start	End
ENSE00001450342	87464020	87464465
ENSE00002077710	87407972	87408089
ENSE00003695074	87461022	87461165
ENSE00003696051	87426526	87426645
ENSE00003697503	87409835	87409947
ENSE00003698131	87428626	87428824
ENSE00003698188	87413810	87413900
ENSE00003699192	87416669	87416827
ENSE00003699818	87410585	87410668
ENSE00003700835	87431033	87431173
ENSE00003701235	87434860	87435053
ENSE00003701755	87418208	87418416
ENSE00003702452	87415686	87415874

Expression profiles

Bgee: expression breadth broad, 99 present calls, max score 92.70.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4491 / max 230.5289, expressed in 466 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68839	1.4491	466

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	92.70	gold quality
left testis	UBERON:0004533	89.59	gold quality
testis	UBERON:0000473	89.46	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.07	gold quality
right testis	UBERON:0004534	88.63	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.03	gold quality
fallopian tube	UBERON:0003889	74.89	gold quality
hypothalamus	UBERON:0001898	63.61	gold quality
ventricular zone	UBERON:0003053	62.59	gold quality
endometrium	UBERON:0001295	61.86	gold quality
adenohypophysis	UBERON:0002196	60.78	gold quality
pituitary gland	UBERON:0000007	60.57	gold quality
Ammon’s horn	UBERON:0001954	59.87	gold quality
superior frontal gyrus	UBERON:0002661	59.69	gold quality
caudate nucleus	UBERON:0001873	59.13	gold quality
right adrenal gland cortex	UBERON:0035827	58.98	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	57.51	gold quality
Brodmann (1909) area 9	UBERON:0013540	57.49	gold quality
right adrenal gland	UBERON:0001233	57.44	gold quality
adult mammalian kidney	UBERON:0000082	57.33	gold quality
cerebral cortex	UBERON:0000956	56.74	gold quality
right lung	UBERON:0002167	56.57	gold quality
amygdala	UBERON:0001876	56.49	gold quality
temporal lobe	UBERON:0001871	56.08	gold quality
cortex of kidney	UBERON:0001225	56.01	gold quality
prefrontal cortex	UBERON:0000451	55.94	gold quality
kidney	UBERON:0002113	55.88	gold quality
anterior cingulate cortex	UBERON:0009835	55.81	gold quality
thyroid gland	UBERON:0002046	55.55	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	7.08
E-ANND-3	yes	6.27

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Bi-allelic truncating variants in CFAP206 cause male infertility in human and mouse. (PMID:34255152)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cfap206	ENSDARG00000021997
mus_musculus	Cfap206	ENSMUSG00000028294
rattus_norvegicus	Cfap206	ENSRNOG00000009061
drosophila_melanogaster	CG13436	FBGN0034532

Protein

Protein identifiers

Cilia- and flagella-associated protein 206 — Q8IYR0 (reviewed: Q8IYR0)

All UniProt accessions (3): Q8IYR0, D6R9L9, D6RBZ4

UniProt curated annotations — full annotation on UniProt →

Function. Essential for sperm motility and is involved in the regulation of the beating frequency of motile cilia on the epithelial cells of the respiratory tract. Required for the establishment of radial spokes in sperm flagella.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme. Cilium basal body.

Similarity. Belongs to the CFAP206 family.

RefSeq proteins (1): NP_001026913* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021897	FAP206	Family

Pfam: PF12018

UniProt features (5 total): sequence variant 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYR0-F1	85.41	0.54

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 98 (showing top): chr6q15, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_MALE_GAMETE_GENERATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_REGULATION_OF_MICROTUBULE_BASED_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MOTILE_CILIUM_ASSEMBLY

GO Biological Process (6): cilium movement (GO:0003341), regulation of cilium beat frequency (GO:0003356), sperm axoneme assembly (GO:0007288), axoneme assembly (GO:0035082), regulation of flagellated sperm motility (GO:1901317), cell projection organization (GO:0030030)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (9): radial spoke (GO:0001534), axoneme (GO:0005930), motile cilium (GO:0031514), ciliary basal body (GO:0036064), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995), A axonemal microtubule (GO:0097649)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cilium	2
microtubule-based movement	1
regulation of cilium movement	1
developmental process involved in reproduction	1
axoneme assembly	1
sperm flagellum assembly	1
microtubule bundle formation	1
cellular component assembly	1
cilium assembly	1
flagellated sperm motility	1
regulation of cilium movement involved in cell motility	1
regulation of reproductive process	1
cellular component organization	1
binding	1
axoneme	1
protein-containing complex	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
microtubule organizing center	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
axonemal microtubule	1
axonemal doublet microtubule	1

Protein interactions and networks

STRING

696 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP206	EFCAB10	A6NFE3	488
CFAP206	FAM153B	P0C7A2	470
CFAP206	CCDC187	A0A096LP49	468
CFAP206	TTC23L	Q6PF05	464
CFAP206	TMCO2	Q7Z6W1	464
CFAP206	STPG2	Q8N412	450
CFAP206	CCDC54	Q8NEL0	449
CFAP206	C6orf163	Q5TEZ5	447
CFAP206	CFAP58	Q5T655	444
CFAP206	RSPH9	Q9H1X1	442
CFAP206	CFAP61	Q8NHU2	441
CFAP206	FAM209A	Q5JX71	440
CFAP206	CXorf65	A6NEN9	436
CFAP206	CFAP263	Q9H0I3	432
CFAP206	C20orf173	Q96LM9	432

IntAct

207 interactions, top by confidence:

A	B	Type	Score
KRT40	CFAP206	psi-mi:“MI:0915”(physical association)	0.720
CFAP206	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.720
CFAP206	GPRASP2	psi-mi:“MI:0915”(physical association)	0.720
GPRASP2	CFAP206	psi-mi:“MI:0915”(physical association)	0.720
ADAMTSL4	CFAP206	psi-mi:“MI:0915”(physical association)	0.720
CFAP206	SOX30	psi-mi:“MI:0915”(physical association)	0.670
UBXN11	CFAP206	psi-mi:“MI:0915”(physical association)	0.670
C1orf94	CFAP206	psi-mi:“MI:0915”(physical association)	0.670
CFAP206	TFIP11	psi-mi:“MI:0915”(physical association)	0.670
CFAP206	UBXN11	psi-mi:“MI:0915”(physical association)	0.670
CFAP206	C1orf94	psi-mi:“MI:0915”(physical association)	0.670
TFIP11	CFAP206	psi-mi:“MI:0915”(physical association)	0.670
	CFAP206	psi-mi:“MI:0915”(physical association)	0.560
CFAP206	GFAP	psi-mi:“MI:0915”(physical association)	0.560
TLE5	CFAP206	psi-mi:“MI:0915”(physical association)	0.560
ROCK1	CFAP206	psi-mi:“MI:0915”(physical association)	0.560
CFAP206	GSE1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (80): C6orf165 (Two-hybrid), C6orf165 (Two-hybrid), C6orf165 (Two-hybrid), C6orf165 (Two-hybrid), C6orf165 (Two-hybrid), C6orf165 (Two-hybrid), C6orf165 (Two-hybrid), C6orf165 (Two-hybrid), C6orf165 (Two-hybrid), C6orf165 (Two-hybrid), C6orf165 (Two-hybrid), C6orf165 (Two-hybrid), C6orf165 (Two-hybrid), C6orf165 (Two-hybrid), C6orf165 (Two-hybrid)

ESM2 similar proteins: A1A5Q4, A1L3F5, B0I564, B1AY13, O15327, O75934, Q0IIE6, Q28DG8, Q29RL1, Q2IA00, Q4R4D7, Q4R6T7, Q4R708, Q5NVD7, Q5RA60, Q5RAX7, Q5RBT3, Q5U1Z0, Q5VZE5, Q5ZHV2, Q62717, Q6DDI6, Q6DFL5, Q6DKG0, Q6GLR7, Q6PBE2, Q6PE87, Q6PHQ8, Q7SYB2, Q7T322, Q7ZXA8, Q86UW7, Q86VS3, Q8BMG7, Q8BYR5, Q8C9J3, Q8CDG3, Q8CF97, Q8CJF7, Q8IYR0

Diamond homologs: A1A5Q4, A2RV06, Q29RL1, Q6PE87, Q8IYR0, Q95JU3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of the cornified envelope	5	14.6×	2e-03
Keratinization	6	11.1×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	6	30.1×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	77
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1027670	NM_001031743.3(CFAP206):c.1430dup (p.Asn477fs)	Pathogenic
4294322	NM_001031743.3(CFAP206):c.1430del (p.Asn477fs)	Pathogenic

SpliceAI

2640 predictions. Top by Δscore:

Variant	Effect	Δscore
6:87409833:A:AG	acceptor_gain	1.0000
6:87409834:G:GG	acceptor_gain	1.0000
6:87409834:GCCA:G	acceptor_gain	1.0000
6:87409946:TGGTA:T	donor_loss	1.0000
6:87409948:G:GA	donor_loss	1.0000
6:87409948:G:GC	donor_loss	1.0000
6:87409948:G:GG	donor_gain	1.0000
6:87409949:T:G	donor_loss	1.0000
6:87410580:TCTAG:T	acceptor_loss	1.0000
6:87410582:TAG:T	acceptor_loss	1.0000
6:87410582:TAGGT:T	acceptor_loss	1.0000
6:87410583:A:AG	acceptor_gain	1.0000
6:87410583:AG:A	acceptor_gain	1.0000
6:87410583:AGGT:A	acceptor_gain	1.0000
6:87410584:G:GG	acceptor_gain	1.0000
6:87410584:G:GT	acceptor_gain	1.0000
6:87410584:GG:G	acceptor_gain	1.0000
6:87410584:GGT:G	acceptor_gain	1.0000
6:87410584:GGTG:G	acceptor_gain	1.0000
6:87410584:GGTGA:G	acceptor_gain	1.0000
6:87410664:TTAAG:T	donor_loss	1.0000
6:87410665:TAAG:T	donor_loss	1.0000
6:87410667:AG:A	donor_loss	1.0000
6:87410667:AGGTG:A	donor_loss	1.0000
6:87410668:GG:G	donor_loss	1.0000
6:87410668:GGT:G	donor_loss	1.0000
6:87410669:G:GA	donor_loss	1.0000
6:87410670:T:A	donor_loss	1.0000
6:87413808:A:AG	acceptor_gain	1.0000
6:87413809:G:GG	acceptor_gain	1.0000

AlphaMissense

4109 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:87416675:T:C	L160P	0.996
6:87416774:G:A	G193E	0.996
6:87416747:T:C	L184P	0.995
6:87416773:G:A	G193R	0.995
6:87416773:G:C	G193R	0.995
6:87418385:G:C	R270P	0.995
6:87431131:T:C	C420R	0.993
6:87428653:T:A	W330R	0.992
6:87428653:T:C	W330R	0.992
6:87434934:T:C	F459L	0.992
6:87434936:T:A	F459L	0.992
6:87434936:T:G	F459L	0.992
6:87416780:G:C	R195P	0.991
6:87410591:G:C	A39P	0.990
6:87416736:A:C	K180N	0.990
6:87416736:A:T	K180N	0.990
6:87431133:T:G	C420W	0.990
6:87434935:T:C	F459S	0.990
6:87410618:T:C	F48L	0.989
6:87410620:T:A	F48L	0.989
6:87410620:T:G	F48L	0.989
6:87410661:T:C	L62P	0.989
6:87434926:C:A	A456E	0.989
6:87413868:A:C	Q84P	0.988
6:87413869:A:C	Q84H	0.988
6:87413869:A:T	Q84H	0.988
6:87416756:T:C	L187P	0.988
6:87416774:G:T	G193V	0.988
6:87410619:T:C	F48S	0.987
6:87413813:T:C	C66R	0.987

dbSNP variants (sampled 300 via entrez): RS1000099270 (6:87429134 G>A,C), RS1000130290 (6:87431961 A>G), RS1000163947 (6:87462363 A>G,T), RS1000241662 (6:87428999 G>A,C), RS1000266180 (6:87411799 CT>C), RS1000346120 (6:87425566 TTGA>T), RS1000420972 (6:87409449 G>A), RS1000448677 (6:87418506 G>A,C), RS1000502355 (6:87413696 TGAATCAATATCAG>T), RS1000511394 (6:87448613 C>G), RS1000552475 (6:87413360 GAA>G), RS1000563560 (6:87448245 T>G), RS1000676027 (6:87427117 A>C), RS1000711582 (6:87461835 A>C), RS1000750535 (6:87441640 G>A)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:621387

GenCC curated gene-disease

Mondo (1): spermatogenic failure 102 (MONDO:0980708)

Orphanet (0):

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003251	Male infertility
HP:0011462	Young adult onset
HP:0012208	Immotile sperm
HP:0032558	Absent sperm flagella
HP:0032559	Short sperm flagella
HP:0032560	Coiled sperm flagella
HP:0032562	Tapered sperm head
HP:0033393	Irregularly shaped sperm tail

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004609_73	Monocyte percentage of white cells	1.000000e-09
GCST004865_34	Itch intensity from mosquito bite adjusted by bite size	9.000000e-06
GCST90002394_166	Monocyte percentage of white cells	2.000000e-23

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007989	monocyte percentage of leukocytes
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	2
bisphenol A	increases methylation	1
perfluorooctane sulfonic acid	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Air Pollutants	increases abundance, increases expression	1
Estradiol	decreases expression	1
Melphalan	decreases expression	1
Rotenone	decreases expression	1
Smoke	increases abundance, increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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