CFAP70

Summary

CFAP70 (cilia and flagella associated protein 70, HGNC:30726) is a protein-coding gene on chromosome 10q22.2, encoding Cilia- and flagella-associated protein 70 (Q5T0N1). Axoneme-binding protein that plays a role in the regulation of ciliary motility and cilium length.

Predicted to be involved in cilium assembly and cilium movement. Predicted to act upstream of or within several processes, including maintenance of cell number; single fertilization; and spermatid development. Located in ciliary basal body and sperm flagellum. Part of outer dynein arm. Implicated in spermatogenic failure 41.

Source: NCBI Gene 118491 — RefSeq curated summary.

At a glance

• Gene–disease (curated): non-syndromic male infertility due to sperm motility disorder (Supportive, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 126 total — 1 pathogenic
• Phenotypes (HPO): 6
• MANE Select transcript: NM_001367801

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30726
Approved symbol	CFAP70
Name	cilia and flagella associated protein 70
Location	10q22.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25765
Ensembl gene	ENSG00000156042
Ensembl biotype	protein_coding
OMIM	618661
Entrez	118491

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000310715, ENST00000340329, ENST00000355577, ENST00000394865, ENST00000433268, ENST00000462684, ENST00000493787, ENST00000495161, ENST00000686590, ENST00000691223

RefSeq mRNA: 3 — MANE Select: NM_001367801 NM_001350933, NM_001350934, NM_001367801

CCDS: CCDS91262, CCDS91263, CCDS91264

Canonical transcript exons

ENST00000355577 — 28 exons

Exon	Start	End
ENSE00002323865	73358778	73358864
ENSE00003375320	73297042	73297173
ENSE00003441020	73293263	73293388
ENSE00003468280	73348156	73348235
ENSE00003473994	73253762	73254055
ENSE00003483978	73348423	73348521
ENSE00003489427	73291640	73291755
ENSE00003506767	73311834	73311914
ENSE00003510066	73310158	73310249
ENSE00003521973	73277240	73277361
ENSE00003523237	73354734	73354835
ENSE00003528355	73291226	73291444
ENSE00003528483	73341399	73341581
ENSE00003533030	73353556	73353742
ENSE00003533234	73298907	73299101
ENSE00003535097	73272928	73273017
ENSE00003545409	73312473	73312643
ENSE00003561677	73291881	73292014
ENSE00003578957	73278179	73278337
ENSE00003591628	73275446	73275598
ENSE00003607290	73274433	73274594
ENSE00003623994	73299605	73299665
ENSE00003624024	73345065	73345244
ENSE00003637865	73269614	73269715
ENSE00003666564	73331177	73331276
ENSE00003672682	73322963	73323097
ENSE00003679341	73256369	73256416
ENSE00003689194	73335430	73335524

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 99.47.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3238 / max 68.7957, expressed in 531 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110049	1.2455	520
110050	0.0783	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.47	gold quality
bronchial epithelial cell	CL:0002328	99.31	gold quality
bronchus	UBERON:0002185	98.41	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.98	gold quality
caput epididymis	UBERON:0004358	95.01	gold quality
oviduct epithelium	UBERON:0004804	92.81	gold quality
adenohypophysis	UBERON:0002196	92.76	gold quality
pituitary gland	UBERON:0000007	92.56	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.43	gold quality
left testis	UBERON:0004533	91.21	gold quality
right testis	UBERON:0004534	91.20	gold quality
testis	UBERON:0000473	89.35	gold quality
fallopian tube	UBERON:0003889	88.33	gold quality
sperm	CL:0000019	88.27	gold quality
corpus epididymis	UBERON:0004359	87.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.06	gold quality
thyroid gland	UBERON:0002046	85.67	gold quality
left lobe of thyroid gland	UBERON:0001120	85.05	gold quality
epithelium of nasopharynx	UBERON:0001951	84.71	gold quality
nasal cavity epithelium	UBERON:0005384	84.61	gold quality
right lobe of thyroid gland	UBERON:0001119	84.29	gold quality
pancreatic ductal cell	CL:0002079	83.35	silver quality
right adrenal gland cortex	UBERON:0035827	82.93	gold quality
right adrenal gland	UBERON:0001233	82.55	gold quality
left adrenal gland cortex	UBERON:0035825	82.42	gold quality
left adrenal gland	UBERON:0001234	81.97	gold quality
tibia	UBERON:0000979	81.82	gold quality
adrenal cortex	UBERON:0001235	81.82	gold quality
nasal cavity mucosa	UBERON:0001826	81.64	gold quality
caudate nucleus	UBERON:0001873	81.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-130148	yes	11.72
E-ANND-3	yes	10.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting CFAP70, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-7973	96.48	65.54	502
HSA-MIR-6808-3P	94.13	65.24	516

Literature-anchored findings (GeneRIF, showing 1)

• CFAP70 mutations lead to male infertility due to severe astheno-teratozoospermia. A case report. (PMID:31621862)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cfap70	ENSDARG00000058508
mus_musculus	Cfap70	ENSMUSG00000039543
rattus_norvegicus	Cfap70	ENSRNOG00000007046

Paralogs (14): IFT88 (ENSG00000032742), TTC7A (ENSG00000068724), TMTC4 (ENSG00000125247), TMTC1 (ENSG00000133687), TMTC3 (ENSG00000139324), TTC6 (ENSG00000139865), BBS4 (ENSG00000140463), TTC13 (ENSG00000143643), OGT (ENSG00000147162), TTC8 (ENSG00000165533), TTC7B (ENSG00000165914), TTC16 (ENSG00000167094), TMTC2 (ENSG00000179104), TTC34 (ENSG00000215912)

Protein

Protein identifiers

Cilia- and flagella-associated protein 70 — Q5T0N1 (reviewed: Q5T0N1)

Alternative names: Tetratricopeptide repeat protein 18

All UniProt accessions (7): Q5T0N1, A0A087WSW1, A0A0A0MS55, A0A8I5KZ08, A0A8J8YUN0, X6R507, X6RID7

UniProt curated annotations — full annotation on UniProt →

Function. Axoneme-binding protein that plays a role in the regulation of ciliary motility and cilium length. Essential for the assembly of the sperm flagellum and the correct shaping of the sperm head, during spermiogenesis.Contributes in part to flagellar biogenesis by stabilizing QRICH2, promoting the cytoplasmic preassembly of CFAP61 and CFAP91, and regulating the manchette localization of axoneme-associated proteins such as IFT88, DNAI1 and CFAP61.

Subunit / interactions. Interacts with MYCBPAP, CFAP65, DNAI1, DNAI2, QRICH2, CFAP61 and CFAP91.

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

Tissue specificity. Expressed in testis.

Disease relevance. Spermatogenic failure 41 (SPGF41) [MIM:618670] An autosomal recessive infertility disorder characterized by oligozoospermia, severe asthenozoospermia and flagellar abnormalities such as short, absent, coiled, and irregular-caliber flagella. Some sperm show tapered heads and acrosomal abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The conserved TPR domains are dispensable for ciliary targeting. The N-terminal half is important for cilary localization and/or binding to the axoneme.

Similarity. Belongs to the CFAP70 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q5T0N1-1	1	yes
Q5T0N1-2	2
Q5T0N1-3	3
Q5T0N1-6	4
Q5T0N1-7	5

RefSeq proteins (3): NP_001337862, NP_001337863, NP_001354730* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR052628	CFAP70	Family

Pfam: PF13181

UniProt features (24 total): repeat 8, splice variant 4, sequence variant 4, region of interest 3, sequence conflict 3, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T0N1-F1	76.55	0.40

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 91 (showing top): GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_ORGANELLE_ASSEMBLY, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, RFX1_02, GOBP_CELL_PROJECTION_ORGANIZATION, TGGAAA_NFAT_Q4_01, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM, GOCC_DYNEIN_COMPLEX, GOCC_CILIUM, GOCC_AXONEMAL_DYNEIN_COMPLEX, GOCC_CILIARY_BASAL_BODY, DODD_NASOPHARYNGEAL_CARCINOMA_DN

GO Biological Process (13): cilium movement (GO:0003341), cilium assembly (GO:0060271), cell morphogenesis (GO:0000902), single fertilization (GO:0007338), intracellular protein localization (GO:0008104), gene expression (GO:0010467), flagellated sperm motility (GO:0030317), cilium organization (GO:0044782), homeostasis of number of cells (GO:0048872), protein-containing complex assembly (GO:0065003), maintenance of cell number (GO:0098727), sperm flagellum assembly (GO:0120316), manchette assembly (GO:1905198)

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

GO Cellular Component (11): axoneme (GO:0005930), motile cilium (GO:0031514), ciliary basal body (GO:0036064), sperm flagellum (GO:0036126), outer dynein arm (GO:0036157), extracellular exosome (GO:0070062), manchette (GO:0002177), 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	4
cellular component assembly	2
spermatid development	2
cilium	2
microtubule-based movement	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
anatomical structure morphogenesis	1
fertilization	1
macromolecule localization	1
macromolecule biosynthetic process	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
organelle organization	1
plasma membrane bounded cell projection organization	1
multicellular organismal-level homeostasis	1
protein-containing complex organization	1
developmental process	1
developmental process involved in reproduction	1
flagellated sperm motility	1
motile cilium assembly	1
binding	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
microtubule organizing center	1
9+2 motile cilium	1
axonemal dynein complex	1
extracellular vesicle	1
microtubule cytoskeleton	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1

Protein interactions and networks

STRING

2073 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP70	CFAP43	Q8NDM7	701
CFAP70	CFAP69	A5D8W1	663
CFAP70	CFAP44	Q96MT7	652
CFAP70	CFAP251	Q8TBY9	637
CFAP70	TTC21A	Q8NDW8	635
CFAP70	TTC29	Q8NA56	630
CFAP70	ARMC2	Q8NEN0	622
CFAP70	QRICH2	Q9H0J4	616
CFAP70	CFAP58	Q5T655	615
CFAP70	CFAP65	Q6ZU64	609
CFAP70	SPEF2	Q9C093	604
CFAP70	CFAP91	Q7Z4T9	596
CFAP70	CFAP47	Q6ZTR5	573
CFAP70	DNAH6	Q9C0G6	572
CFAP70	FSIP2	Q5CZC0	570

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ECE1	CFAP70	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (6): CFAP70 (Affinity Capture-MS), CFAP70 (Negative Genetic), HSP90AA1 (Cross-Linking-MS (XL-MS)), CFAP70 (Affinity Capture-MS), CFAP70 (Cross-Linking-MS (XL-MS)), CFAP70 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JEB6, A0JM56, B0DOB4, B0FXQ5, B1ANS9, B4F7L9, B4GQJ7, B5DHW4, B7FF06, B7FF07, B7FF08, B7FF09, B7FF12, C5IAW9, F1LW30, F1P4W9, O08747, O95185, P0DM40, Q008S8, Q18264, Q32NR9, Q3V0B4, Q402B2, Q4G0P3, Q5R4M2, Q5T0N1, Q5XI14, Q6AXU1, Q6DCF6, Q6NRS1, Q6P2C0, Q6P5D8, Q6UXZ4, Q6ZTR5, Q6ZU64, Q761X5, Q7T2Z5, Q80W93, Q86YR7

Diamond homologs: D3YVL2, Q5T0N1, Q95LN2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	102
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
694584	NM_001367801.1(CFAP70):c.1723-1G>T	Pathogenic

SpliceAI

5122 predictions. Top by Δscore:

Variant	Effect	Δscore
10:73256363:TCATA:T	donor_loss	1.0000
10:73256364:CATA:C	donor_loss	1.0000
10:73256365:ATAC:A	donor_loss	1.0000
10:73256366:TA:T	donor_loss	1.0000
10:73256367:A:AT	donor_loss	1.0000
10:73256368:C:CG	donor_loss	1.0000
10:73269612:A:AC	donor_gain	1.0000
10:73269613:C:CC	donor_gain	1.0000
10:73274595:C:CC	acceptor_gain	1.0000
10:73275595:CATA:C	acceptor_gain	1.0000
10:73275597:TA:T	acceptor_gain	1.0000
10:73275599:C:CC	acceptor_gain	1.0000
10:73291302:C:A	donor_gain	1.0000
10:73291309:T:A	donor_gain	1.0000
10:73291348:A:AC	donor_gain	1.0000
10:73291349:C:CC	donor_gain	1.0000
10:73293390:T:C	acceptor_gain	1.0000
10:73293400:CAAGA:C	acceptor_gain	1.0000
10:73293401:A:T	acceptor_gain	1.0000
10:73293404:A:AC	acceptor_gain	1.0000
10:73293404:A:C	acceptor_gain	1.0000
10:73293407:T:C	acceptor_gain	1.0000
10:73293407:T:TC	acceptor_gain	1.0000
10:73293411:G:GC	acceptor_gain	1.0000
10:73293416:C:CT	acceptor_gain	1.0000
10:73298901:TTTTA:T	donor_loss	1.0000
10:73298902:TTTAC:T	donor_loss	1.0000
10:73298903:TTAC:T	donor_loss	1.0000
10:73298904:TACC:T	donor_loss	1.0000
10:73298905:A:T	donor_loss	1.0000

AlphaMissense

7339 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:73335476:A:G	W281R	0.998
10:73335476:A:T	W281R	0.998
10:73269684:A:G	L1056P	0.997
10:73269697:C:G	A1052P	0.997
10:73348453:C:G	A107P	0.996
10:73269676:C:G	A1059P	0.995
10:73293310:C:G	A645P	0.995
10:73323054:A:T	V344D	0.995
10:73323066:C:T	G340D	0.995
10:73291444:C:T	G744D	0.994
10:73322997:A:T	V363D	0.994
10:73323060:G:T	A342D	0.994
10:73323061:C:G	A342P	0.994
10:73335510:C:A	R269S	0.994
10:73335510:C:G	R269S	0.994
10:73345151:C:G	A175P	0.994
10:73345228:A:T	V149D	0.994
10:73269643:A:G	W1070R	0.993
10:73269643:A:T	W1070R	0.993
10:73272929:C:G	R1045P	0.993
10:73272945:C:G	G1040R	0.993
10:73272945:C:T	G1040R	0.993
10:73291640:C:G	G744R	0.993
10:73291755:G:C	S705R	0.993
10:73291755:G:T	S705R	0.993
10:73291882:T:G	S705R	0.993
10:73269633:A:G	L1073P	0.992
10:73291741:C:T	G710D	0.992
10:73331245:A:G	W307R	0.992
10:73331245:A:T	W307R	0.992

dbSNP variants (sampled 300 via entrez): RS1000026344 (10:73304500 T>A,C), RS1000050514 (10:73289288 A>C), RS1000098722 (10:73296600 C>G,T), RS1000173975 (10:73261578 A>C,T), RS1000183239 (10:73269471 C>T), RS1000229012 (10:73324430 T>G), RS1000290897 (10:73261592 A>T), RS1000309964 (10:73317275 C>T), RS1000348720 (10:73254834 T>C), RS1000396683 (10:73303376 C>A), RS1000453681 (10:73269254 C>A), RS1000461523 (10:73304204 C>A), RS1000520711 (10:73267606 A>C,G), RS1000577984 (10:73267326 T>A,C), RS1000642103 (10:73339457 CCT>C)

Disease associations

OMIM: gene MIM:618661 | disease phenotypes: MIM:618670

GenCC curated gene-disease

Disease	Classification	Inheritance
non-syndromic male infertility due to sperm motility disorder	Supportive	Autosomal recessive

Mondo (2): spermatogenic failure 41 (MONDO:0032863), (MONDO:0017173)

Orphanet (0):

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000798	Oligozoospermia
HP:0003251	Male infertility
HP:0012208	Immotile sperm
HP:0032559	Short sperm flagella
HP:0032562	Tapered sperm head

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002386_405	High light scatter reticulocyte percentage of red cells	1.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Nickel	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases methylation	1
2,3-pentanedione	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
avobenzone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
NSC 689534	affects binding, increases expression	1
Sunitinib	increases expression	1
Arbutin	decreases expression	1
Copper	affects binding, increases expression	1
Diacetyl	decreases expression	1
Estradiol	decreases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
N-Nitrosopyrrolidine	decreases expression	1
Niclosamide	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
S-Nitrosoglutathione	decreases expression	1

Clinical trials (associated diseases)

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