CFAP61

Summary

CFAP61 (cilia and flagella associated protein 61, HGNC:15872) is a protein-coding gene on chromosome 20p11.23, encoding Cilia- and flagella-associated protein 61 (Q8NHU2). Involved in sperm flagellum assembly.

Involved in sperm flagellum assembly. Predicted to be located in motile cilium and radial spoke stalk. Predicted to be active in sperm flagellum. Implicated in spermatogenic failure 84.

Source: NCBI Gene 26074 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 245 total — 8 pathogenic
• Phenotypes (HPO): 11
• MANE Select transcript: NM_015585

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15872
Approved symbol	CFAP61
Name	cilia and flagella associated protein 61
Location	20p11.23
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434K156, dJ1002M8.3, CaM-IP3
Ensembl gene	ENSG00000089101
Ensembl biotype	protein_coding
OMIM	620381
Entrez	26074

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 17 protein_coding, 6 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 3 retained_intron

ENST00000245957, ENST00000340348, ENST00000377293, ENST00000377303, ENST00000377306, ENST00000377308, ENST00000389656, ENST00000431753, ENST00000442372, ENST00000451767, ENST00000468719, ENST00000469994, ENST00000472660, ENST00000475466, ENST00000476414, ENST00000486624, ENST00000488640, ENST00000493330, ENST00000494029, ENST00000497372, ENST00000674269, ENST00000674296, ENST00000674445, ENST00000674463, ENST00000884932, ENST00000884933, ENST00000884934, ENST00000884935, ENST00000884936, ENST00000884937

RefSeq mRNA: 2 — MANE Select: NM_015585 NM_001167816, NM_015585

CCDS: CCDS33447, CCDS54452

Canonical transcript exons

ENST00000245957 — 27 exons

Exon	Start	End
ENSE00001594211	20262956	20263130
ENSE00001602021	20277166	20277458
ENSE00003465164	20290300	20290391
ENSE00003468439	20098655	20098814
ENSE00003471017	20070854	20071004
ENSE00003486942	20075189	20075256
ENSE00003502373	20196570	20196776
ENSE00003505335	20166397	20166436
ENSE00003505730	20191342	20191419
ENSE00003507903	20251595	20251763
ENSE00003536236	20169321	20169460
ENSE00003543813	20075489	20075615
ENSE00003545995	20142857	20142948
ENSE00003555646	20246117	20246215
ENSE00003562412	20298181	20298386
ENSE00003569193	20341831	20341921
ENSE00003575692	20187930	20188056
ENSE00003589138	20159370	20159444
ENSE00003622209	20164050	20164228
ENSE00003648116	20090844	20090976
ENSE00003670284	20056618	20056796
ENSE00003673658	20288609	20288936
ENSE00003676460	20199768	20199902
ENSE00003676821	20074302	20074378
ENSE00003690727	20360210	20360698
ENSE00003758687	20228249	20228376
ENSE00003842071	20052532	20052591

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 95.53.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9286 / max 111.7762, expressed in 240 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183765	0.5234	173
183768	0.2696	49
183769	0.0493	14
183767	0.0370	19
183766	0.0335	23
183771	0.0158	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	95.53	gold quality
gastrocnemius	UBERON:0001388	93.83	gold quality
right uterine tube	UBERON:0001302	92.51	gold quality
muscle of leg	UBERON:0001383	91.69	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.34	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.40	gold quality
left testis	UBERON:0004533	87.76	gold quality
right testis	UBERON:0004534	87.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.70	gold quality
heart left ventricle	UBERON:0002084	84.97	gold quality
testis	UBERON:0000473	84.67	gold quality
apex of heart	UBERON:0002098	84.46	gold quality
cardiac ventricle	UBERON:0002082	84.02	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.56	gold quality
bronchial epithelial cell	CL:0002328	81.70	gold quality
bronchus	UBERON:0002185	79.86	gold quality
adenohypophysis	UBERON:0002196	79.52	gold quality
pituitary gland	UBERON:0000007	79.44	gold quality
tibialis anterior	UBERON:0001385	75.27	silver quality
islet of Langerhans	UBERON:0000006	73.11	gold quality
secondary oocyte	CL:0000655	72.28	gold quality
ventricular zone	UBERON:0003053	72.24	gold quality
heart	UBERON:0000948	70.84	gold quality
hypothalamus	UBERON:0001898	70.74	gold quality
caudate nucleus	UBERON:0001873	69.16	gold quality
skeletal muscle tissue	UBERON:0001134	68.94	gold quality
calcaneal tendon	UBERON:0003701	68.63	gold quality
right lung	UBERON:0002167	68.49	gold quality
prefrontal cortex	UBERON:0000451	68.11	gold quality
nucleus accumbens	UBERON:0001882	68.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.84

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting CFAP61, 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-4533	100.00	69.48	2758
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-603	98.58	68.28	1603
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-1246	98.54	66.21	959
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-628-5P	98.36	67.74	844
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-6728-5P	97.79	66.33	891
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-4695-3P	96.71	67.21	836

Literature-anchored findings (GeneRIF, showing 4)

• CFAP61 is required for sperm flagellum formation and male fertility in human and mouse. (PMID:34792097)
• Biallelic CFAP61 variants cause male infertility in humans and mice with severe oligoasthenoteratozoospermia. (PMID:35387802)
• CFAP61 knockdown aggravates male infertility by inhibiting testosterone secretion by Leydig cells via the MAPK/COX-2 pathway. (PMID:37982895)
• Identification of a novel CFAP61 homozygous splicing variant associated with multiple morphological abnormalities of the flagella. (PMID:38775994)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:zfos-223e1.2	ENSDARG00000079997
mus_musculus	Cfap61	ENSMUSG00000037143
rattus_norvegicus	Cfap61	ENSRNOG00000011028
drosophila_melanogaster	CG30268	FBGN0050268
drosophila_melanogaster	CG30275	FBGN0050275

Protein

Protein identifiers

Cilia- and flagella-associated protein 61 — Q8NHU2 (reviewed: Q8NHU2)

All UniProt accessions (10): Q8NHU2, A0A6I8PIN3, A0A6I8PRQ8, C9J610, C9JA66, C9JHE8, C9JMV0, F8W6E2, F8WDF5, H0Y3Y7

UniProt curated annotations — full annotation on UniProt →

Function. Involved in sperm flagellum assembly. Plays an essential role in the formation of the radial spokes in flagellum axoneme.

Subunit / interactions. Component of axonemal radial spokes, the protein complexes that link the outer microtubule doublets with the central pair of microtubules. Interacts with CFAP91/MAATS1, ODAD2/ARMC4, RSPH3A, ROPN1, ROPN1L and RSPH9. Interacts with DYNLT1, DYNC1I2 and TUBB3. Interacts with WDR35, IFT22 and IFT81. Interacts with CFAP70.

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

Disease relevance. Spermatogenic failure 84 (SPGF84) [MIM:620409] An autosomal recessive male infertility disorder characterized by multiple morphologic abnormalities of the sperm flagella, resulting in severely reduced motility. Some patients also have a reduced sperm count. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Created from a fragment entry and may await further characterization.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8NHU2-1	1	yes
Q8NHU2-3	3
Q8NHU2-4	4
Q8NHU2-5	5
Q8NHU2-6	6

RefSeq proteins (2): NP_001161288, NP_056400* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032151	CFAP61_N	Domain
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily
IPR038884	CFAP61	Family
IPR056299	CFAP61_dimer	Domain

Pfam: PF16092, PF23150

UniProt features (25 total): sequence variant 12, splice variant 8, sequence conflict 2, chain 1, region of interest 1, compositionally biased region 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-Q8NHU2-F1	84.86	0.57

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 101 (showing top): GOBP_MALE_GAMETE_GENERATION, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MOTILE_CILIUM_ASSEMBLY, GOBP_CELL_PROJECTION_ORGANIZATION, MODULE_95, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOCC_CILIUM, chr20p11

GO Biological Process (5): cilium movement (GO:0003341), flagellated sperm motility (GO:0030317), cilium organization (GO:0044782), sperm flagellum assembly (GO:0120316), sperm mitochondrial sheath assembly (GO:0120317)

GO Molecular Function (0):

GO Cellular Component (9): axoneme (GO:0005930), motile cilium (GO:0031514), sperm flagellum (GO:0036126), radial spoke stalk (GO:0001536), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
microtubule-based movement	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
developmental process involved in reproduction	1
spermatid development	1
flagellated sperm motility	1
motile cilium assembly	1
cellular component assembly	1
sperm flagellum assembly	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
cilium	1
9+2 motile cilium	1
radial spoke	1
protein-containing complex	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

640 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP61	CFAP251	Q8TBY9	784
CFAP61	CFAP91	Q7Z4T9	769
CFAP61	SPMAP2L	P0DJG4	626
CFAP61	SPMIP1	A0A1B0GUX0	623
CFAP61	CFAP58	Q5T655	606
CFAP61	NAA20	P61599	590
CFAP61	RSPH3	Q86UC2	588
CFAP61	CRNKL1	Q9BZJ0	563
CFAP61	CFAP43	Q8NDM7	526
CFAP61	CFAP70	Q5T0N1	512
CFAP61	RALGAPA2	Q2PPJ7	495
CFAP61	CCDC127	Q96BQ5	483
CFAP61	DRC11	Q86XH1	456
CFAP61	DRC5	Q5JU00	451
CFAP61	DRC7	Q8IY82	446

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CFAP61	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (2): CFAP61 (Affinity Capture-MS), CFAP61 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A1KXW8, A6QL50, E1BGQ2, H0Y354, O94955, P47224, Q08326, Q0IIH8, Q1JQA1, Q1RMS8, Q1RMZ1, Q2TBU5, Q3T1H6, Q4R372, Q4R528, Q4R9C4, Q5F480, Q5F4A1, Q5I0G3, Q5RCQ0, Q5RFG8, Q5TFE4, Q5TYM5, Q641X7, Q6L9T8, Q6PIP5, Q7L622, Q7Z6J8, Q7ZX59, Q86X60, Q8BFZ8, Q8BKW4, Q8BM85, Q8BX13, Q8CEL2, Q8N5C7, Q8N635, Q8NHU2, Q8TCF1, Q8TCJ0

Diamond homologs: O00370, P08548, P11369, Q8CEL2, Q8NHU2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	0
Uncertain significance	197
Likely benign	17
Benign	0

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1526686	GRCh37/hg19 20p11.23-11.22(chr20:19292925-22187397)	Pathogenic
2504100	NM_015585.4(CFAP61):c.143+5G>A	Pathogenic
2504101	NM_015585.4(CFAP61):c.452_453del (p.Ile151fs)	Pathogenic
2504102	NM_015585.4(CFAP61):c.847C>T (p.Arg283Ter)	Pathogenic
2504103	NM_015585.4(CFAP61):c.1654C>T (p.Arg552Cys)	Pathogenic
2504104	NM_015585.4(CFAP61):c.2911G>A (p.Asp971Asn)	Pathogenic
2504105	NM_015585.4(CFAP61):c.144-2A>G	Pathogenic
2504106	NM_015585.4(CFAP61):c.1666G>A (p.Gly556Arg)	Pathogenic

SpliceAI

5494 predictions. Top by Δscore:

Variant	Effect	Δscore
20:20052729:GGGA:G	donor_gain	1.0000
20:20052730:GGAG:G	donor_gain	1.0000
20:20070840:A:AG	acceptor_gain	1.0000
20:20071000:GCACA:G	donor_gain	1.0000
20:20071001:CACAG:C	donor_loss	1.0000
20:20071002:ACAG:A	donor_loss	1.0000
20:20071003:CAG:C	donor_loss	1.0000
20:20071004:AGTAA:A	donor_loss	1.0000
20:20071005:G:GG	donor_gain	1.0000
20:20071005:GTAA:G	donor_loss	1.0000
20:20071006:T:G	donor_loss	1.0000
20:20074296:CTGCA:C	acceptor_loss	1.0000
20:20074297:T:A	acceptor_gain	1.0000
20:20074297:TGCA:T	acceptor_loss	1.0000
20:20074298:GCA:G	acceptor_loss	1.0000
20:20074299:CAGC:C	acceptor_loss	1.0000
20:20074300:A:AG	acceptor_gain	1.0000
20:20074300:A:G	acceptor_loss	1.0000
20:20074301:G:GC	acceptor_gain	1.0000
20:20074301:GC:G	acceptor_gain	1.0000
20:20074301:GCC:G	acceptor_gain	1.0000
20:20074301:GCCC:G	acceptor_gain	1.0000
20:20074301:GCCCC:G	acceptor_gain	1.0000
20:20074378:GGTG:G	donor_loss	1.0000
20:20074379:G:GG	donor_gain	1.0000
20:20074380:T:A	donor_loss	1.0000
20:20164170:G:T	donor_gain	1.0000
20:20169461:G:GG	donor_gain	1.0000
20:20187925:CCCA:C	acceptor_loss	1.0000
20:20187926:CCAG:C	acceptor_loss	1.0000

AlphaMissense

8230 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:20251735:T:C	L767P	0.997
20:20070906:G:C	A66P	0.996
20:20070912:G:C	A68P	0.996
20:20070960:T:A	W84R	0.995
20:20070960:T:C	W84R	0.995
20:20246146:T:C	L697P	0.995
20:20070907:C:A	A66D	0.994
20:20098673:G:T	G240W	0.994
20:20098674:G:A	G240E	0.994
20:20288739:C:A	A976D	0.994
20:20290330:T:C	L1052P	0.994
20:20360379:T:C	L1228P	0.994
20:20090864:T:C	L196P	0.993
20:20098673:G:A	G240R	0.993
20:20098673:G:C	G240R	0.993
20:20196718:G:C	R580P	0.993
20:20228325:T:A	V670E	0.993
20:20251735:T:A	L767H	0.993
20:20251745:C:G	C770W	0.993
20:20288738:G:C	A976P	0.993
20:20075230:T:C	L138P	0.992
20:20228358:T:C	L681P	0.992
20:20288820:G:A	G1003D	0.992
20:20288829:T:C	L1006P	0.992
20:20070868:T:C	L53P	0.991
20:20074317:T:C	F104L	0.991
20:20074319:C:A	F104L	0.991
20:20074319:C:G	F104L	0.991
20:20251696:T:A	V754D	0.991
20:20277378:T:A	W906R	0.991

dbSNP variants (sampled 300 via entrez): RS1000009642 (20:20149494 G>T), RS1000018099 (20:20119696 A>G), RS1000031970 (20:20067407 A>G), RS1000049185 (20:20113889 A>G), RS1000057838 (20:20243983 G>A), RS1000058303 (20:20249912 G>A,C), RS1000067386 (20:20206624 G>T), RS1000071988 (20:20340411 A>G), RS1000092155 (20:20127289 G>C,T), RS1000099191 (20:20073071 A>C,G), RS1000118533 (20:20077664 G>T), RS1000122150 (20:20344846 A>C,G), RS1000125897 (20:20232895 G>A), RS1000126489 (20:20302785 A>C,G), RS1000136119 (20:20193390 G>A,T)

Disease associations

OMIM: gene MIM:620381 | disease phenotypes: MIM:620409

GenCC curated gene-disease

Mondo (1): spermatogenic failure 84 (MONDO:0957301)

Orphanet (0):

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000798	Oligozoospermia
HP:0003251	Male infertility
HP:0011462	Young adult onset
HP:0012207	Reduced sperm motility
HP:0032558	Absent sperm flagella
HP:0032559	Short sperm flagella
HP:0032560	Coiled sperm flagella
HP:0033393	Irregularly shaped sperm tail
HP:0034011	Reduced progressive sperm motility
HP:0034811	Bent sperm flagella

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004141_1	Body fat mass	2.000000e-09
GCST007576_127	Chronotype	2.000000e-08
GCST008163_616	Height	9.000000e-06
GCST010314_6	Serum omega-6 to omega-3 polyunsaturated fatty acid ratio in metabolic syndrome	8.000000e-06
GCST90000025_634	Appendicular lean mass	5.000000e-20
GCST90000025_635	Appendicular lean mass	5.000000e-12
GCST90002389_417	Lymphocyte percentage of white cells	1.000000e-10
GCST90002399_449	Neutrophil percentage of white cells	8.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0010732	omega-6:omega-3 polyunsaturated fatty acid ratio
EFO:0004980	appendicular lean mass
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases mutagenesis	2
bisphenol F	affects cotreatment, decreases methylation	1
bisphenol A	decreases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
tebuconazole	decreases expression	1
bisphenol S	increases methylation	1
Fulvestrant	affects cotreatment, decreases methylation	1
Doxorubicin	decreases expression	1
Methapyrilene	increases methylation	1
Methylcholanthrene	affects binding, increases reaction	1
Rotenone	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Tunicamycin	increases expression	1
Valproic Acid	decreases methylation	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	decreases methylation	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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