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.

Acts upstream of or within sperm mitochondrial sheath assembly. Located in axoneme and sperm flagellum. Implicated in spermatogenic failure 84.

Source: NCBI Gene 26074 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 247 total — 7 pathogenic, 2 likely-pathogenic
• GTEx eGene: eQTL in 19 tissues, sQTL in 4 (q < 0.05)
• Phenotypes (HPO): 11
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.89 (unconstrained)
• MANE Select transcript: NM_015585
• Notable: 247 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 34 — 21 protein_coding, 6 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 3 retained_intron

MANE Select: ENST00000245957

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 2, TSL 3: 3, TSL 4: 4, TSL 5: 6

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, ENST00001128518, ENST00001128519, ENST00001128520, ENST00001133369

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.

Highest expression (Bgee): buccal mucosa cell, gastrocnemius, uterine tube, muscle of leg, primordial germ cell in gonad.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CFAP61 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 19 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 23 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	sqtl	3.1e-54	+0.82	20:20330695:A:G
Thyroid	eqtl	1.0e-25	+0.64	20:20045783:A:T
Muscle Skeletal	eqtl	3.8e-19	-0.33	20:20086057:C:T
Artery Aorta	eqtl	7.6e-17	-0.52	20:20086057:C:T
Brain Frontal Cortex BA9	eqtl	3.0e-14	-0.53	20:20052723:C:G
Testis	eqtl	2.9e-11	-0.15	20:20020142:T:A
Brain Cortex	eqtl	3.7e-10	-0.51	20:20052779:G:A
Brain Anterior cingulate cortex BA24	eqtl	1.6e-08	-0.40	20:20036999:T:C
Skin Sun Exposed Lower leg	eqtl	3.0e-08	-0.30	20:20103305:T:C
Testis	sqtl	1.6e-06	+0.68	20:20067209:A:G
Brain Hippocampus	eqtl	3.7e-06	-0.27	20:20063329:T:C
Brain Nucleus accumbens basal ganglia	eqtl	7.4e-05	-0.22	20:20034548:T:TAAAC
Brain Substantia nigra	eqtl	1.9e-04	+1.37	20:20084679:G:A
Heart Atrial Appendage	eqtl	3.1e-04	+0.30	20:20091770:C:T
Pituitary	eqtl	6.7e-04	-0.25	20:20086057:C:T
Heart Left Ventricle	sqtl	1.0e-03	+0.31	20:20322732:G:A
Brain Caudate basal ganglia	eqtl	2.1e-03	-0.14	20:20078348:G:A
Lung	eqtl	2.9e-03	-0.36	20:20931745:C:T
Brain Spinal cord cervical c-1	eqtl	6.3e-03	+1.75	20:20084679:G:A
Skin Not Sun Exposed Suprapubic	eqtl	6.7e-03	+0.44	20:20120512:T:C

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

showing 100 of 249 tissues 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
deltoid	UBERON:0001476	67.87	silver quality
left ventricle myocardium	UBERON:0006566	66.59	gold quality
fallopian tube	UBERON:0003889	66.51	gold quality
muscle tissue	UBERON:0002385	65.91	gold quality
putamen	UBERON:0001874	65.06	gold quality
Brodmann (1909) area 9	UBERON:0013540	64.78	gold quality
right frontal lobe	UBERON:0002810	64.50	gold quality
heart right ventricle	UBERON:0002080	64.34	silver quality
pancreatic ductal cell	CL:0002079	64.25	silver quality
cortical plate	UBERON:0005343	63.88	gold quality
nasal cavity mucosa	UBERON:0001826	63.66	gold quality
anterior cingulate cortex	UBERON:0009835	63.32	gold quality
forebrain	UBERON:0001890	62.99	gold quality
upper arm skin	UBERON:0004263	62.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	62.80	gold quality
neocortex	UBERON:0001950	62.43	gold quality
frontal cortex	UBERON:0001870	62.32	gold quality
brain	UBERON:0000955	62.03	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	61.78	gold quality
skin of leg	UBERON:0001511	61.68	gold quality
myocardium	UBERON:0002349	61.68	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	61.29	gold quality
ganglionic eminence	UBERON:0004023	61.18	gold quality
cerebellar hemisphere	UBERON:0002245	61.10	gold quality
cerebellar cortex	UBERON:0002129	61.09	gold quality
amygdala	UBERON:0001876	60.91	gold quality
substantia nigra	UBERON:0002038	60.67	gold quality
nasal cavity epithelium	UBERON:0005384	60.04	gold quality
spinal cord	UBERON:0002240	59.97	gold quality
cerebral cortex	UBERON:0000956	59.85	gold quality
cerebellum	UBERON:0002037	59.83	gold quality
caput epididymis	UBERON:0004358	59.68	gold quality
adult mammalian kidney	UBERON:0000082	59.54	gold quality
tendon	UBERON:0000043	59.23	gold quality
biceps brachii	UBERON:0001507	59.14	silver quality
oviduct epithelium	UBERON:0004804	59.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	59.01	silver quality
primary visual cortex	UBERON:0002436	58.96	gold quality
midbrain	UBERON:0001891	58.70	gold quality
upper leg skin	UBERON:0004262	58.63	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	58.63	gold quality
corpus callosum	UBERON:0002336	58.56	gold quality
Ammon’s horn	UBERON:0001954	57.72	gold quality
thyroid gland	UBERON:0002046	57.62	gold quality
left lobe of thyroid gland	UBERON:0001120	57.36	gold quality
right atrium auricular region	UBERON:0006631	57.34	gold quality
descending thoracic aorta	UBERON:0002345	57.32	gold quality
endocervix	UBERON:0000458	57.31	gold quality
right lobe of thyroid gland	UBERON:0001119	57.26	gold quality
upper lobe of left lung	UBERON:0008952	56.95	gold quality
cardiac atrium	UBERON:0002081	56.94	gold quality
zone of skin	UBERON:0000014	56.90	gold quality
granulocyte	CL:0000094	56.68	gold quality
pancreas	UBERON:0001264	55.89	gold quality
left uterine tube	UBERON:0001303	55.82	gold quality
upper lobe of lung	UBERON:0008948	55.81	gold quality
skin of abdomen	UBERON:0001416	55.73	gold quality
substantia nigra pars reticulata	UBERON:0001966	55.56	gold quality
lung	UBERON:0002048	55.20	gold quality
epithelial cell of pancreas	CL:0000083	55.17	gold quality
anatomical system	UBERON:0000467	55.17	gold quality
multicellular organism	UBERON:0000468	54.96	gold quality
material anatomical entity	UBERON:0000465	54.94	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
subcutaneous adipose tissue	UBERON:0002190	54.30	gold quality
pericardium	UBERON:0002407	54.22	gold quality
cerebellar vermis	UBERON:0004720	54.18	gold quality
occipital lobe	UBERON:0002021	54.17	gold quality
temporal lobe	UBERON:0001871	53.99	gold quality
kidney epithelium	UBERON:0004819	53.93	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 65 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	37.2	medium
Periaqueductal gray	tissue	20.4
Cerebellum	tissue	18.2	not detected
Olfactory bulb	tissue	14.7
Testis	tissue	14.5	medium
Basal ganglia	tissue	13.5	low
Hippocampal formation	tissue	11.9
Heart muscle	tissue	11.6	low
Fallopian tube	tissue	11.4	high
Hypothalamus	tissue	11.1
Septum	tissue	10.0
Tongue	tissue	9.5
Skeletal muscle	tissue	9.4	low
Corpus callosum	tissue	8.9
Amygdala	tissue	7.7
Pons	tissue	7.5
Thalamus	tissue	6.7
Ventral forebrain	tissue	6.7
Nucleus accumbens	tissue	6.4
Midbrain	tissue	6.1
Medulla oblongata	tissue	5.8
Substantia nigra	tissue	5.8
Putamen	tissue	5.7
Prefrontal cortex	tissue	5.3
Cerebral cortex	tissue	5.3	not detected
Retrosplenial cortex	tissue	5.0
Locus coeruleus	tissue	4.8
Somatosensory cortex	tissue	4.7
Superior colliculi	tissue	4.4
Retrosplenial and cingulate cortex	tissue	4.4
Temporal cortex	tissue	4.4
Insular cortex	tissue	4.4
Hippocampus	tissue	4.2	not detected
Entorhinal cortex	tissue	4.1
Occipital cortex	tissue	4.1
Motor cortex	tissue	3.9
Postcentral gyrus	tissue	3.4
Pituitary gland	tissue	2.9
Spinal cord	tissue	2.3
Frontal cortex	tissue	2.0
Retina	tissue	1.7
Caudate putamen	tissue	1.6
Lung	tissue	1.2	not detected
Epididymis	tissue	0.9
Thyroid gland	tissue	0.7	not detected
Kidney	tissue	0.7	not detected
Endometrium 1	tissue	0.6	not detected
Adrenal gland	tissue	0.6	low
Parathyroid gland	tissue	0.5	not detected
Cervix	tissue	0.4	not detected
Pancreas	tissue	0.3	not detected
Prostate	tissue	0.3	not detected
Breast	tissue	0.2	not detected
Ovary	tissue	0.2	not detected
Seminal vesicle	tissue	0.2	not detected
Skin 1	tissue	0.1	not detected
Lymph node	tissue	0.1	not detected
Stomach 1	tissue	0.1	not detected
Vagina	tissue	0.1	not detected
Smooth muscle	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Periaquaductal grey, lateral (18.4), Nucleus tractus solitarii (14.0), Dorsal hippocampus (11.9), Cervical spinal cord, central gray (11.8), Periaquaductal grey, dorsal (10.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CFAP61 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

24 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 3.88e-22, LOEUF 0.892, missense Z 0.976 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000245957 — one region, missense o/e 0.97.

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1926024) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 18 distinct phenotype terms.

Mouse phenotype (MP)	Records
male infertility	3
oligozoospermia	2
absent sperm flagellum	2
abnormal sperm flagellum morphology	2
coiled sperm flagellum	2
short sperm flagellum	2
abnormal sperm axoneme morphology	2
abnormal spermiogenesis	1
asthenozoospermia	1
increased blood urea nitrogen level	1
kinked sperm flagellum	1
thick sperm flagellum	1
decreased bone mineral content	1
increased testis apoptosis	1
decreased sperm progressive motility	1
immotile sperm	1
abnormal outer dense fiber morphology	1
abnormal sperm radial spoke morphology	1

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
INSM1	protein-coding	3642
CFAP61-AS1	ncRNA	101929575
CRNKL1	protein-coding	51340
RALGAPA2	protein-coding	57186
NAA20	protein-coding	51126
RIN2	protein-coding	54453
SLC24A3-AS1	ncRNA	100130264
SLC24A3	protein-coding	57419

Protein

Protein identifiers

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

All UniProt accessions (10): A0A6I8PIN3, A0A6I8PRQ8, C9J610, C9JA66, C9JHE8, C9JMV0, Q8NHU2, 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 by resolution:

PDB	Title	Method	Resolution (Å)
8J07	96nm repeat of human respiratory doublet microtubule and associated axonemal complexes	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NHU2-F1	84.86	0.57

Human Protein Atlas

Protein class: Predicted membrane proteins, Predicted intracellular proteins, UniProt - Evidence at transcript level

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; principal piece; nucleoplasm

Antibody reliability (HPA): IH approved · IF approved

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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 Cellular Component (6): axoneme (GO:0005930), motile cilium (GO:0031514), sperm flagellum (GO:0036126), radial spoke stalk (GO:0001536), cytoskeleton (GO:0005856), cilium (GO:0005929)

GO top-level categories

24 GO namespaces:

Category	Terms
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
cellular anatomical structure	1
cilium	1
9+2 motile cilium	1
radial spoke	1
protein-containing complex	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
flagellated sperm motility	BP	mutant phenotype
sperm flagellum assembly	BP	mutant phenotype
sperm mitochondrial sheath assembly	BP	mutant phenotype
axoneme	CC	direct assay
sperm flagellum	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,072 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP61	CFAP91	Q7Z4T9	745
CFAP61	CFAP251	Q8TBY9	716
CFAP61	CFAP70	Q5T0N1	658
CFAP61	RSPH3	Q86UC2	636
CFAP61	CFAP58	Q5T655	629
CFAP61	NAA20	P61599	618
CFAP61	CFAP206	Q8IYR0	603
CFAP61	CRNKL1	Q9BZJ0	602
CFAP61	CFAP43	Q8NDM7	600
CFAP61	SPMIP1	A0A1B0GUX0	597
CFAP61	CFAP44	Q96MT7	595
CFAP61	SPMAP2L	P0DJG4	588
CFAP61	RSPH9	Q9H1X1	574
CFAP61	DNAH1	Q9P2D7	555
CFAP61	RSPH1	Q8WYR4	527

IntAct

BioGRID (3 interactions; top human partners by supporting records): ATP6V0A1 (Cross-Linking-MS (XL-MS)), PARK2 (Affinity Capture-MS), PARP10 (Proximity Label-MS)

Disease & clinical

Genetic variants

Variant evidence for CFAP61: 247 ClinVar records (9 pathogenic / likely pathogenic); 8 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	2
Uncertain significance	197
Likely benign	17
Benign	0

Top pathogenic / likely-pathogenic (9)

Showing all 9 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2504102	NM_015585.4(CFAP61):c.847C>T (p.Arg283Ter)	Pathogenic	criteria provided, single submitter	2
4850446	NM_015585.4(CFAP61):c.3125-1G>C	Likely pathogenic	criteria provided, single submitter	1
4853824	NM_015585.4(CFAP61):c.2264T>C (p.Val755Ala)	Likely pathogenic	criteria provided, single submitter	1
1526686	GRCh37/hg19 20p11.23-11.22(chr20:19292925-22187397)x1	Pathogenic	criteria provided, single submitter	1
2504100	NM_015585.4(CFAP61):c.143+5G>A	Pathogenic	no assertion criteria provided	1
2504101	NM_015585.4(CFAP61):c.452_453del (p.Ile151fs)	Pathogenic	no assertion criteria provided	1
2504104	NM_015585.4(CFAP61):c.2911G>A (p.Asp971Asn)	Pathogenic	no assertion criteria provided	1
2504105	NM_015585.4(CFAP61):c.144-2A>G	Pathogenic	no assertion criteria provided	1
2504106	NM_015585.4(CFAP61):c.1666G>A (p.Gly556Arg)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CFAP61’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 42 predictions of 2,910):

Position(s)	Effect	Δscore	Sites
20:20071005–20071006	donor_loss	1.0000	5
20:20074297	acceptor_gain	1.0000
20:20074300–20074301	acceptor_loss	1.0000	6
20:20074379–20074380	donor_loss	1.0000	5
20:20164170	donor_gain	1.0000
20:20187928–20187929	acceptor_loss	1.0000	5
20:20188057–20188058	donor_loss	1.0000	4
20:20196777–20196778	donor_loss	1.0000	5
20:20251764–20251765	donor_loss	1.0000	5
20:20263131–20263132	donor_loss	1.0000	5

AlphaMissense

2,107 missense substitutions predicted likely pathogenic (of 8,230 scored), across 625 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D192	8	0.974	0.990
D72	8	0.934	0.980
D1154	8	0.933	0.971
F104	8	0.930	0.991
F154	8	0.905	0.982
H1153	8	0.901	0.948
D23	8	0.898	0.954
F920	8	0.898	0.988
D272	8	0.869	0.942
D194	8	0.850	0.921
D405	8	0.839	0.927
F241	8	0.831	0.985
F1087	8	0.830	0.965
H555	8	0.816	0.946
D473	8	0.814	0.858
M1230	8	0.801	0.909
F1143	8	0.790	0.979
F70	8	0.773	0.986
D1158	8	0.749	0.853
D493	8	0.747	0.855

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme)

Disease associations

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

GenCC curated gene-disease

Mondo (2): spermatogenic failure 84 (MONDO:0957301), situs inversus (MONDO:0010029)

Orphanet (1): Situs inversus totalis (Orphanet:101063)

HPO phenotypes

11 phenotypes (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:

Study	Trait	p-value
GCST90000025_84	Appendicular lean mass	5e-20
GCST90002399_185	Neutrophil percentage of white cells	8e-13
GCST90000025_85	Appendicular lean mass	5e-12
GCST90002389_478	Lymphocyte percentage of white cells	1e-10
GCST004141_1	Body fat mass	2e-9
GCST007576_65	Chronotype	2e-8
GCST010314_6	Serum omega-6 to omega-3 polyunsaturated fatty acid ratio in metabolic syndrome	8e-6
GCST008163_591	Height	9e-6

EFO canonical traits (from GWAS)

5 canonical traits:

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

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D012857	Situs Inversus	C16.131.810

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases mutagenesis, affects methylation	2
bisphenol F	decreases methylation, affects cotreatment	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	increases reaction, affects binding	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)

Via MONDO — disease-level, not drug-specific.

1 trials:

NCT	Phase	Status	Title
NCT00608556	Not specified	COMPLETED	Dyskinesia, Heterotaxy and Congenital Heart Disease