CFAP58

Summary

CFAP58 (cilia and flagella associated protein 58, HGNC:26676) is a protein-coding gene on chromosome 10q25.1, encoding Cilia- and flagella-associated protein 58 (Q5T655). Has an essential role in the assembly and organization of the sperm flagellar axoneme.

Involved in protein localization to motile cilium; sperm axoneme assembly; and sperm mitochondrial sheath assembly. Located in sperm midpiece. Implicated in spermatogenic failure 49.

Source: NCBI Gene 159686 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 158 total — 5 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 7
• MANE Select transcript: NM_001008723

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26676
Approved symbol	CFAP58
Name	cilia and flagella associated protein 58
Location	10q25.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ35908, bA554P13.1
Ensembl gene	ENSG00000120051
Ensembl biotype	protein_coding
OMIM	619129
Entrez	159686

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000369703, ENST00000369704

RefSeq mRNA: 3 — MANE Select: NM_001008723 NM_001008723, NM_001400226, NM_001400227

CCDS: CCDS31282

Canonical transcript exons

ENST00000369704 — 18 exons

Exon	Start	End
ENSE00000811739	104380029	104380220
ENSE00001250545	104392233	104392394
ENSE00001399870	104400680	104400903
ENSE00001400765	104447698	104447817
ENSE00001403092	104403729	104403840
ENSE00001413587	104399360	104399500
ENSE00001415022	104406689	104406793
ENSE00001422019	104450071	104450204
ENSE00001435812	104393329	104393475
ENSE00001450682	104353833	104353906
ENSE00001861447	104454422	104455102
ENSE00003496500	104370895	104371054
ENSE00003503049	104362023	104362171
ENSE00003539295	104364733	104364889
ENSE00003584282	104368423	104368560
ENSE00003621690	104376811	104376893
ENSE00003682437	104365814	104366008
ENSE00003683479	104358341	104358622

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 99.29.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3268 / max 67.6608, expressed in 70 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106893	0.3016	61
106892	0.0252	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.29	gold quality
secondary oocyte	CL:0000655	98.78	gold quality
bronchial epithelial cell	CL:0002328	91.25	gold quality
bronchus	UBERON:0002185	88.99	gold quality
right uterine tube	UBERON:0001302	88.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.35	gold quality
pancreatic ductal cell	CL:0002079	83.92	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.58	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.81	gold quality
left testis	UBERON:0004533	79.78	gold quality
mucosa of paranasal sinus	UBERON:0005030	79.29	gold quality
sperm	CL:0000019	78.28	gold quality
right testis	UBERON:0004534	77.85	gold quality
testis	UBERON:0000473	77.16	gold quality
oviduct epithelium	UBERON:0004804	74.92	gold quality
epithelium of nasopharynx	UBERON:0001951	72.69	silver quality
fallopian tube	UBERON:0003889	72.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	70.09	gold quality
right atrium auricular region	UBERON:0006631	69.43	gold quality
cardiac atrium	UBERON:0002081	68.22	gold quality
apex of heart	UBERON:0002098	67.46	gold quality
ganglionic eminence	UBERON:0004023	67.06	gold quality
stromal cell of endometrium	CL:0002255	66.71	gold quality
tibialis anterior	UBERON:0001385	65.40	silver quality
heart left ventricle	UBERON:0002084	65.38	gold quality
cardiac ventricle	UBERON:0002082	64.54	gold quality
heart	UBERON:0000948	63.94	gold quality
right lung	UBERON:0002167	62.98	gold quality
endocervix	UBERON:0000458	62.40	gold quality
nasal cavity mucosa	UBERON:0001826	61.51	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.18
E-MTAB-8060	no	82.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting CFAP58, 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-371B-5P	99.99	75.34	4759
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-106A-3P	99.53	67.58	995
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-569	99.42	66.32	1009
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-6818-3P	98.56	68.23	1307
HSA-MIR-548AO-5P	98.55	69.57	1362
HSA-MIR-548AX	98.55	69.58	1362
HSA-MIR-654-3P	98.38	67.61	905
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-6834-3P	98.16	65.77	551

Literature-anchored findings (GeneRIF, showing 3)

• A heterozygous p.Arg696Cys variant in the coiled-coil domain containing 147 gene at 10q25.1 was associated with Lung Cancer. (PMID:26762739)
• Bi-allelic Loss-of-function Variants in CFAP58 Cause Flagellar Axoneme and Mitochondrial Sheath Defects and Asthenoteratozoospermia in Humans and Mice. (PMID:32791035)
• Biallelic mutations of CFAP58 are associated with multiple morphological abnormalities of the sperm flagella. (PMID:33314088)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cfap58	ENSDARG00000069435
mus_musculus	Cfap58	ENSMUSG00000046585
rattus_norvegicus	Cfap58	ENSRNOG00000049596
drosophila_melanogaster	CG5882	FBGN0039490

Paralogs (1): CCDC146 (ENSG00000135205)

Protein

Protein identifiers

Cilia- and flagella-associated protein 58 — Q5T655 (reviewed: Q5T655)

Alternative names: Coiled-coil domain-containing protein 147

All UniProt accessions (2): Q5T655, Q9H4Y4

UniProt curated annotations — full annotation on UniProt →

Function. Has an essential role in the assembly and organization of the sperm flagellar axoneme. Required for the elongation of the primary cilium and sperm flagellar midpiece via modulation of the Notch signaling pathway.

Subunit / interactions. Interacts with ODFP2.

Subcellular location. Cell projection. Cilium. Flagellum. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Disease relevance. Spermatogenic failure 49 (SPGF49) [MIM:619144] An autosomal recessive infertility disorder characterized by asthenoteratozoospermia and multiple morphologic abnormalities of the sperm flagella, primarily coiled and short flagella, with markedly reduced or absent motility. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CFAP58 family.

RefSeq proteins (3): NP_001008723, NP_001387155, NP_001387156 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR049270	CFAP58_CC	Domain

Pfam: PF21771

UniProt features (12 total): sequence variant 9, coiled-coil region 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T655-F1	79.87	0.14

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 77 (showing top): GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_MALE_GAMETE_GENERATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOCC_CENTROSOME, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MOTILE_CILIUM_ASSEMBLY, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_AXONEME_ASSEMBLY

GO Biological Process (8): Notch signaling pathway (GO:0007219), sperm axoneme assembly (GO:0007288), flagellated sperm motility (GO:0030317), cilium assembly (GO:0060271), protein localization to motile cilium (GO:0120229), sperm flagellum assembly (GO:0120316), sperm mitochondrial sheath assembly (GO:0120317), cell projection organization (GO:0030030)

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

GO Cellular Component (9): obsolete extracellular space (GO:0005615), centrosome (GO:0005813), cytoskeleton (GO:0005856), sperm flagellum (GO:0036126), sperm midpiece (GO:0097225), cytoplasm (GO:0005737), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
developmental process involved in reproduction	2
axoneme assembly	2
sperm flagellum assembly	2
protein localization to cilium	2
cell surface receptor signaling pathway	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
spermatid development	1
flagellated sperm motility	1
motile cilium assembly	1
cellular component assembly	1
cellular component organization	1
binding	1
centriole	1
microtubule organizing center	1
intracellular membraneless organelle	1
9+2 motile cilium	1
sperm flagellum	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

536 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP58	CFAP43	Q8NDM7	670
CFAP58	TTC29	Q8NA56	629
CFAP58	CFAP70	Q5T0N1	615
CFAP58	TTC21A	Q8NDW8	613
CFAP58	CFAP61	Q8NHU2	606
CFAP58	ARMC2	Q8NEN0	596
CFAP58	CFAP44	Q96MT7	594
CFAP58	CFAP251	Q8TBY9	582
CFAP58	CFAP69	A5D8W1	582
CFAP58	QRICH2	Q9H0J4	581
CFAP58	CFAP91	Q7Z4T9	517
CFAP58	SPEF2	Q9C093	494
CFAP58	DNAH17	Q9UFH2	475
CFAP58	DNAH6	Q9C0G6	464
CFAP58	FLYWCH1	Q4VC44	459

IntAct

18 interactions, top by confidence:

A	B	Type	Score
CFAP58	NAV2	psi-mi:“MI:0915”(physical association)	0.560
NAV2	CFAP58	psi-mi:“MI:0915”(physical association)	0.560
CFAP58	BACH2	psi-mi:“MI:0915”(physical association)	0.560
CFAP58	KRT27	psi-mi:“MI:0915”(physical association)	0.560
MCC	CFAP58	psi-mi:“MI:0915”(physical association)	0.560
RIPPLY1	CFAP58	psi-mi:“MI:0915”(physical association)	0.560
CFAP58	H1-5	psi-mi:“MI:0915”(physical association)	0.400
TRAF3IP1	CFAP58	psi-mi:“MI:0915”(physical association)	0.000
CFAP58	BACH2	psi-mi:“MI:0915”(physical association)	0.000
CFAP58	KRT27	psi-mi:“MI:0915”(physical association)	0.000
CFAP58	MCC	psi-mi:“MI:0915”(physical association)	0.000
RIPPLY1	CFAP58	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): CFAP58 (Two-hybrid), CFAP58 (Co-fractionation), CFAP58 (Reconstituted Complex), CFAP58 (Two-hybrid), RIPPLY1 (Two-hybrid), MCC (Two-hybrid), KRT27 (Two-hybrid), CFAP58 (Two-hybrid), CFAP58 (Proximity Label-MS), CFAP58 (Affinity Capture-MS), CFAP58 (Cross-Linking-MS (XL-MS)), EEA1 (Cross-Linking-MS (XL-MS)), SARNP (Cross-Linking-MS (XL-MS)), ZC3H13 (Cross-Linking-MS (XL-MS)), CFAP58 (Affinity Capture-MS)

ESM2 similar proteins: A0PJP4, A2VDP1, A5D7M3, B2RW38, D3ZUQ0, F1QNW4, O00291, O14645, O43805, O75146, O75150, O95995, Q17QG3, Q26630, Q3U319, Q499U4, Q4FZV3, Q4R3K5, Q4R7K7, Q4R7Y8, Q4V328, Q5DTM8, Q5E9C3, Q5EBL4, Q5RAU7, Q5T655, Q5VTR2, Q5ZLS3, Q60779, Q68CZ1, Q6DGZ3, Q6GN86, Q7XJ96, Q7Z3E2, Q8BKE9, Q8BR07, Q8BVN8, Q8C9S4, Q8CG73, Q8CJB9

Diamond homologs: A8HUA1, B2RW38, Q5T655

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	133
Likely benign	10
Benign	2

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
992189	NM_001008723.2(CFAP58):c.2092C>T (p.Arg698Ter)	Pathogenic
992190	NM_001008723.2(CFAP58):c.1429del (p.Lys476_Ile477insTer)	Pathogenic
992191	NM_001008723.2(CFAP58):c.2052del (p.His685fs)	Pathogenic
992192	NM_001008723.2(CFAP58):c.1696C>T (p.Gln566Ter)	Pathogenic
992193	NM_001008723.2(CFAP58):c.2274C>A (p.Tyr758Ter)	Pathogenic
2439022	NM_001008723.2(CFAP58):c.1360C>T (p.Gln454Ter)	Likely pathogenic

SpliceAI

3440 predictions. Top by Δscore:

Variant	Effect	Δscore
10:104358340:G:A	acceptor_loss	1.0000
10:104358340:GGAAA:G	acceptor_gain	1.0000
10:104358619:GAAG:G	donor_gain	1.0000
10:104358623:GTCA:G	donor_loss	1.0000
10:104358624:T:A	donor_loss	1.0000
10:104362172:G:GG	donor_gain	1.0000
10:104364731:A:AG	acceptor_gain	1.0000
10:104364732:G:GG	acceptor_gain	1.0000
10:104364732:GC:G	acceptor_gain	1.0000
10:104364866:G:GT	donor_gain	1.0000
10:104364915:G:GT	donor_gain	1.0000
10:104364916:A:T	donor_gain	1.0000
10:104364933:G:GT	donor_gain	1.0000
10:104365802:C:CA	acceptor_gain	1.0000
10:104365805:A:AG	acceptor_gain	1.0000
10:104365806:A:AG	acceptor_gain	1.0000
10:104365812:A:AG	acceptor_gain	1.0000
10:104365813:G:GT	acceptor_gain	1.0000
10:104365813:GT:G	acceptor_gain	1.0000
10:104365813:GTT:G	acceptor_gain	1.0000
10:104365813:GTTC:G	acceptor_gain	1.0000
10:104365813:GTTCC:G	acceptor_gain	1.0000
10:104366005:GAAG:G	donor_gain	1.0000
10:104366006:AAG:A	donor_gain	1.0000
10:104366007:AG:A	donor_gain	1.0000
10:104366008:GG:G	donor_gain	1.0000
10:104366009:G:GG	donor_gain	1.0000
10:104366009:GT:G	donor_loss	1.0000
10:104368561:G:GG	donor_gain	1.0000
10:104368573:T:G	donor_gain	1.0000

AlphaMissense

5820 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:104358615:T:C	L95P	1.000
10:104362035:G:C	A102P	0.999
10:104362056:G:C	A109P	0.999
10:104399439:T:C	L585P	0.999
10:104399459:G:C	A592P	0.999
10:104358531:T:C	L67P	0.998
10:104358572:G:C	A81P	0.998
10:104358582:T:C	L84P	0.998
10:104400714:T:C	L617P	0.998
10:104358510:T:C	L60P	0.997
10:104358554:T:C	S75P	0.997
10:104362036:C:A	A102D	0.997
10:104400723:G:C	R620P	0.997
10:104358536:G:C	A69P	0.996
10:104358573:C:A	A81D	0.996
10:104358576:T:C	L82P	0.996
10:104362077:G:C	A116P	0.996
10:104362099:T:C	L123P	0.996
10:104362120:T:C	L130P	0.996
10:104358566:G:C	A79P	0.994
10:104358584:T:C	S85P	0.994
10:104358557:G:C	A76P	0.993
10:104362038:T:A	W103R	0.993
10:104362038:T:C	W103R	0.993
10:104362040:G:C	W103C	0.993
10:104362040:G:T	W103C	0.993
10:104365995:T:C	L260P	0.993
10:104399418:A:C	Q578P	0.993
10:104400702:T:C	L613P	0.993
10:104400720:G:C	R619P	0.993

dbSNP variants (sampled 300 via entrez): RS1000014029 (10:104409889 A>C,G), RS1000019057 (10:104404530 A>G,T), RS1000065272 (10:104452433 A>G), RS1000066904 (10:104376037 G>T), RS1000087210 (10:104409587 G>A), RS1000146957 (10:104364649 C>T), RS1000155879 (10:104404205 T>C), RS1000156035 (10:104384039 C>T), RS1000179163 (10:104427450 A>G), RS1000278355 (10:104434252 T>C), RS1000338807 (10:104397546 T>G), RS1000371449 (10:104397156 A>T), RS1000402237 (10:104448752 G>A,C), RS1000416562 (10:104440023 C>T), RS1000542061 (10:104435646 C>T)

Disease associations

OMIM: gene MIM:619129 | disease phenotypes: MIM:619144

GenCC curated gene-disease

Mondo (1): spermatogenic failure 49 (MONDO:0030868)

Orphanet (0):

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003251	Male infertility
HP:0003581	Adult onset
HP:0012207	Reduced sperm motility
HP:0032558	Absent sperm flagella
HP:0032559	Short sperm flagella
HP:0032560	Coiled sperm flagella

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002590_13	Vascular brain injury	3.000000e-06
GCST002590_4	Vascular brain injury	3.000000e-06
GCST009391_1366	Metabolite levels	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006800	vascular brain injury measurement
EFO:0010366	lysophosphatidylethanolamine 16:0 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases expression, decreases methylation	2
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
tebuconazole	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Demecolcine	increases expression	1
Formaldehyde	increases expression	1
Oxygen	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cadmium Chloride	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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