CFAP43

Summary

CFAP43 (cilia and flagella associated protein 43, HGNC:26684) is a protein-coding gene on chromosome 10q25.1, encoding Cilia- and flagella-associated protein 43 (Q8NDM7). Flagellar protein involved in sperm flagellum axoneme organization and function.

This gene encodes a member of the cilia- and flagella-associated protein family.

Source: NCBI Gene 80217 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure 19 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 334 total — 15 pathogenic, 9 likely-pathogenic (top 10% of genes corpus-wide)
• GTEx eGene: eQTL in 43 tissues, sQTL in 7 (q < 0.05)
• Phenotypes (HPO): 14
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.78 (unconstrained)
• MANE Select transcript: NM_025145
• Interaction hub: 2,923 STRING partners (top 3% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26684
Approved symbol	CFAP43
Name	cilia and flagella associated protein 43
Location	10q25.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ36006, bA373N18.2, FLJ22944
Ensembl gene	ENSG00000197748
Ensembl biotype	protein_coding
OMIM	617558
Entrez	80217

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000357060

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

ENST00000357060, ENST00000278064, ENST00000369719, ENST00000369720, ENST00000434629, ENST00000457071, ENST00000479392, ENST00000956220, ENST00001105675, ENST00001118952, ENST00001129645

RefSeq mRNA: 1 — MANE Select: NM_025145 NM_025145

CCDS: CCDS31281

Canonical transcript exons

ENST00000357060 — 38 exons

Exon	Start	End
ENSE00000987450	104133620	104133784
ENSE00000987451	104132116	104132196
ENSE00000987452	104131331	104131484
ENSE00000987669	104225461	104225557
ENSE00000987670	104214259	104214426
ENSE00000987671	104212007	104212157
ENSE00000987672	104207665	104207824
ENSE00001026118	104197922	104198038
ENSE00001092477	104152607	104152726
ENSE00001092480	104147891	104147998
ENSE00001092484	104187320	104187492
ENSE00001092486	104185974	104186123
ENSE00001092487	104188270	104188410
ENSE00001161163	104203672	104203803
ENSE00001177021	104192199	104192302
ENSE00001191037	104196853	104196933
ENSE00001191088	104193866	104194014
ENSE00001254645	104168744	104168848
ENSE00001254649	104172410	104172535
ENSE00001254659	104179029	104179106
ENSE00001254668	104179840	104179932
ENSE00001254679	104182366	104182513
ENSE00001254685	104185016	104185146
ENSE00001255161	104142281	104142393
ENSE00001255171	104143426	104143639
ENSE00001255179	104145476	104145564
ENSE00001255182	104146263	104146349
ENSE00001255205	104129888	104130305
ENSE00001417865	104167621	104167737
ENSE00001422209	104164094	104164300
ENSE00001424694	104166488	104166718
ENSE00001426182	104161961	104162041
ENSE00001429978	104162317	104162403
ENSE00001432745	104161037	104161162
ENSE00001450723	104205963	104206030
ENSE00003622003	104232182	104232364
ENSE00003641146	104140842	104141001
ENSE00003678708	104230590	104230843

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 99.45.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7415 / max 90.2170, expressed in 526 samples.

Highest expression (Bgee): uterine tube, bronchial epithelial cell, mucosa of paranasal sinus, olfactory segment of nasal mucosa, testis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CFAP43 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 43 tissues and its splicing (sQTL) in 7 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 50 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	1.4e-72	+1.72	10:104167702:C:T
Thyroid	eqtl	1.0e-43	+0.39	10:104211120:T:C
Nerve Tibial	eqtl	1.9e-43	+0.58	10:104214223:C:G
Thyroid	sqtl	2.8e-39	-0.70	10:104150893:A:T
Cells Cultured fibroblasts	eqtl	3.4e-19	+0.44	10:104214575:A:C
Pancreas	eqtl	9.1e-19	+0.53	10:104214223:C:G
Skin Sun Exposed Lower leg	eqtl	8.3e-16	+0.41	10:104211120:T:C
Adrenal Gland	eqtl	1.5e-15	+0.55	10:104173380:T:C
Pituitary	eqtl	1.3e-14	+0.49	10:104214223:C:G
Colon Transverse	eqtl	6.0e-13	+0.43	10:104214575:A:C
Pituitary	sqtl	9.7e-13	+0.79	10:104123637:A:C
Skin Not Sun Exposed Suprapubic	eqtl	1.1e-12	+0.41	10:104214575:A:C
Esophagus Mucosa	eqtl	1.9e-12	+0.42	10:104214575:A:C
Adipose Subcutaneous	eqtl	2.2e-12	+0.39	10:104218932:A:T
Brain Frontal Cortex BA9	eqtl	4.8e-11	+0.50	10:104173380:T:C
Stomach	eqtl	1.6e-09	+0.47	10:104214223:C:G
Brain Anterior cingulate cortex BA24	eqtl	1.7e-08	+0.50	10:104173659:C:A
Colon Sigmoid	eqtl	2.3e-08	+0.35	10:104214575:A:C
Brain Nucleus accumbens basal ganglia	eqtl	3.4e-08	+0.27	10:104175056:A:G
Esophagus Muscularis	eqtl	7.4e-08	+0.36	10:104214223:C:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
111301	1.7415	526

Top tissues by expression

showing 100 of 281 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.45	gold quality
bronchial epithelial cell	CL:0002328	99.12	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.73	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.86	gold quality
left testis	UBERON:0004533	93.67	gold quality
right testis	UBERON:0004534	93.47	gold quality
testis	UBERON:0000473	91.43	gold quality
caput epididymis	UBERON:0004358	90.94	gold quality
epithelium of nasopharynx	UBERON:0001951	89.88	gold quality
epithelium of bronchus	UBERON:0002031	89.40	gold quality
bronchus	UBERON:0002185	89.02	gold quality
sperm	CL:0000019	89.00	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.80	gold quality
male germ cell	CL:0000015	85.67	gold quality
adenohypophysis	UBERON:0002196	83.66	gold quality
pituitary gland	UBERON:0000007	82.84	gold quality
left uterine tube	UBERON:0001303	82.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.19	gold quality
right lung	UBERON:0002167	80.82	gold quality
fallopian tube	UBERON:0003889	80.67	gold quality
metanephros cortex	UBERON:0010533	78.30	gold quality
caudate nucleus	UBERON:0001873	77.74	gold quality
thyroid gland	UBERON:0002046	77.37	gold quality
left lobe of thyroid gland	UBERON:0001120	77.03	gold quality
endometrium	UBERON:0001295	76.85	gold quality
right lobe of thyroid gland	UBERON:0001119	76.82	gold quality
nucleus accumbens	UBERON:0001882	75.68	gold quality
corpus callosum	UBERON:0002336	74.73	gold quality
endocervix	UBERON:0000458	73.62	gold quality
ventricular zone	UBERON:0003053	73.39	gold quality
nasal cavity mucosa	UBERON:0001826	73.36	gold quality
hypothalamus	UBERON:0001898	72.85	gold quality
corpus epididymis	UBERON:0004359	72.36	gold quality
body of pancreas	UBERON:0001150	72.05	gold quality
oviduct epithelium	UBERON:0004804	71.88	gold quality
superior vestibular nucleus	UBERON:0007227	71.71	gold quality
cauda epididymis	UBERON:0004360	71.24	gold quality
amygdala	UBERON:0001876	71.04	gold quality
buccal mucosa cell	CL:0002336	70.00	silver quality
trachea	UBERON:0003126	69.97	gold quality
pancreas	UBERON:0001264	69.60	gold quality
Ammon’s horn	UBERON:0001954	69.57	gold quality
nasal cavity epithelium	UBERON:0005384	69.37	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	69.09	gold quality
Brodmann (1909) area 9	UBERON:0013540	68.53	gold quality
upper lobe of left lung	UBERON:0008952	68.46	gold quality
islet of Langerhans	UBERON:0000006	68.40	gold quality
anterior cingulate cortex	UBERON:0009835	68.40	gold quality
cingulate cortex	UBERON:0003027	68.33	gold quality
right frontal lobe	UBERON:0002810	68.27	gold quality
upper lobe of lung	UBERON:0008948	68.24	gold quality
adult organism	UBERON:0007023	68.08	gold quality
putamen	UBERON:0001874	68.07	gold quality
left ovary	UBERON:0002119	67.93	gold quality
forebrain	UBERON:0001890	67.86	gold quality
germinal epithelium of ovary	UBERON:0001304	67.62	gold quality
cortical plate	UBERON:0005343	67.62	gold quality
lung	UBERON:0002048	67.37	gold quality
ovary	UBERON:0000992	67.20	gold quality
spinal cord	UBERON:0002240	67.01	gold quality
lower lobe of lung	UBERON:0008949	66.92	silver quality
brain	UBERON:0000955	66.49	gold quality
adult mammalian kidney	UBERON:0000082	66.47	gold quality
uterus	UBERON:0000995	66.41	gold quality
telencephalon	UBERON:0001893	66.24	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	66.12	gold quality
right adrenal gland cortex	UBERON:0035827	65.87	gold quality
right ovary	UBERON:0002118	65.76	gold quality
right adrenal gland	UBERON:0001233	65.04	gold quality
left adrenal gland	UBERON:0001234	64.98	gold quality
tibial nerve	UBERON:0001323	64.62	gold quality
gall bladder	UBERON:0002110	64.34	gold quality
body of uterus	UBERON:0009853	64.11	gold quality
female reproductive system	UBERON:0000474	63.88	gold quality
cerebral cortex	UBERON:0000956	63.73	gold quality
kidney	UBERON:0002113	63.70	gold quality
cerebellar hemisphere	UBERON:0002245	63.67	gold quality
prefrontal cortex	UBERON:0000451	63.64	gold quality
cerebellar cortex	UBERON:0002129	63.60	gold quality
neocortex	UBERON:0001950	63.53	gold quality
calcaneal tendon	UBERON:0003701	63.34	gold quality
right hemisphere of cerebellum	UBERON:0014890	63.31	gold quality
ganglionic eminence	UBERON:0004023	63.13	gold quality
left adrenal gland cortex	UBERON:0035825	62.95	gold quality
frontal cortex	UBERON:0001870	62.55	gold quality
adrenal gland	UBERON:0002369	62.37	gold quality
cerebellum	UBERON:0002037	62.05	gold quality
cortex of kidney	UBERON:0001225	62.00	gold quality
adrenal cortex	UBERON:0001235	61.94	gold quality
minor salivary gland	UBERON:0001830	61.71	gold quality
temporal lobe	UBERON:0001871	61.71	gold quality
substantia nigra	UBERON:0002038	61.22	gold quality
metanephros	UBERON:0000081	61.08	gold quality
prostate gland	UBERON:0002367	60.73	gold quality
seminal vesicle	UBERON:0000998	60.63	silver quality
pigmented layer of retina	UBERON:0001782	60.52	silver quality
ectocervix	UBERON:0012249	60.04	gold quality
midbrain	UBERON:0001891	59.73	gold quality
uterine cervix	UBERON:0000002	59.49	gold quality
left ventricle myocardium	UBERON:0006566	59.11	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1815.29
E-CURD-114	yes	62.30
E-MTAB-10287	yes	24.80
E-GEOD-130148	yes	14.44
E-ANND-3	yes	11.39
E-MTAB-9388	yes	6.92

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 67 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Choroid plexus	tissue	166.8
Testis	tissue	53.6
Fallopian tube	tissue	46.0
Nucleus accumbens	tissue	15.3
Locus coeruleus	tissue	10.3
Retina	tissue	9.9
Pituitary gland	tissue	9.7
Hippocampus	tissue	8.0
Lung	tissue	7.7
Periaqueductal gray	tissue	7.6
Epididymis	tissue	7.3
Postcentral gyrus	tissue	4.8
Thyroid gland	tissue	4.5
Parathyroid gland	tissue	3.5
Cervix	tissue	2.9
Endometrium 1	tissue	2.7
Breast	tissue	2.4
Kidney	tissue	2.4
Basal ganglia	tissue	2.3
Hypothalamus	tissue	1.8
Pons	tissue	1.6
Hippocampal formation	tissue	1.6
Septum	tissue	1.5
Seminal vesicle	tissue	1.2
Ovary	tissue	1.1
Pancreas	tissue	1.1
Prostate	tissue	1.1
Skin 1	tissue	0.9
Gallbladder	tissue	0.9
Caudate putamen	tissue	0.9
Salivary gland	tissue	0.8
Thalamus	tissue	0.8
Stomach 1	tissue	0.6
Amygdala	tissue	0.6
Medulla oblongata	tissue	0.6
Corpus callosum	tissue	0.6
Vagina	tissue	0.5
Small intestine	tissue	0.5
Adrenal gland	tissue	0.5
Midbrain	tissue	0.4
Liver	tissue	0.4
Duodenum	tissue	0.4
Thymus	tissue	0.4
Lymph node	tissue	0.3
Frontal cortex	tissue	0.3
Placenta	tissue	0.3
Ventral forebrain	tissue	0.3
Rectum	tissue	0.2
Smooth muscle	tissue	0.2
Colon	tissue	0.2
Superior colliculi	tissue	0.2
Spleen	tissue	0.2
Spinal cord	tissue	0.2
Tonsil	tissue	0.2
Olfactory bulb	tissue	0.2
Appendix	tissue	0.2
Prefrontal cortex	tissue	0.1
Heart muscle	tissue	0.1
Cerebral cortex	tissue	0.1
Adipose tissue	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Periaquaductal grey, lateral (75.0), Nucleus tractus solitarii (74.4), Cervical spinal cord, central gray (51.1), Superior vestibular nucleus (50.9), Periaquaductal grey, dorsal (50.5).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CFAP43 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

15 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-3149	98.77	67.13	1639

Functional genomics

gnomAD constraint: pLI 2.03e-26, LOEUF 0.78, missense Z 1.9 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000357060 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
10:104,130,142–104,140,875	211 / 230.6	0.91	no
10:104,140,876–104,140,988	14 / 38.5	0.36	no
10:104,140,989–104,232,246	1553 / 1685.2	0.92	no

Literature-anchored findings (GeneRIF, showing 7)

• biallelic mutations in either CFAP43 or CFAP44 can cause sperm flagellar abnormalities and impair sperm motility. (PMID:28552195)
• Study demonstrated that biallelic mutations in CFAP44 and CFAP43 cause multiple morphological abnormalities of the sperm flagella (MMAF). These results provide researchers with a new insight to understand the genetic etiology of MMAF and to identify new loci for genetic counselling of MMAF. (PMID:29277146)
• demonstrate that CFAP43 and CFAP44 have a similar structure with a unique axonemal localization and are necessary to produce functional flagella in species ranging from Trypanosoma to human (PMID:29449551)
• important cause of multiple morphological abnormalities of the sperm flagellum in the Chinese population (PMID:30904354)
• A loss of function mutation was identified in a family with normal-pressure hydrocephalus. (PMID:31004071)
• Mutational effect of human CFAP43 splice-site variant causing multiple morphological abnormalities of the sperm flagella. (PMID:32207550)
• Novel biallelic loss-of-function mutations in CFAP43 cause multiple morphological abnormalities of the sperm flagellum in Pakistani families. (PMID:34100391)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cfap43	ENSDARG00000001825
mus_musculus	Cfap43	ENSMUSG00000044948
rattus_norvegicus	Cfap43	ENSRNOG00000036585
drosophila_melanogaster	CG17687	FBGN0036348

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1289258) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 25 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal sperm flagellum morphology	3
male infertility	2
coiled sperm flagellum	2
short sperm flagellum	2
abnormal sperm axoneme morphology	2
absent sperm axonemal central pair	2
dilated lateral ventricle	1
dilated third ventricle	1
hydrocephaly	1
abnormal cauda epididymis morphology	1
asthenozoospermia	1
oligozoospermia	1
teratozoospermia	1
absent sperm flagellum	1
abnormal sperm head morphology	1
kinked sperm flagellum	1
thick sperm flagellum	1
abnormal respiratory motile cilium morphology	1
prenatal lethality, incomplete penetrance	1
abnormal motile cilium morphology	1
decreased sperm progressive motility	1
immotile sperm	1
abnormal sperm flagellum thickness	1
abnormal outer dense fiber morphology	1
abnormal sperm radial spoke morphology	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Xenopus laevis	A0A1L8GXY4	44.9%	Diamond

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
SFR1	protein-coding	119392
COL17A1	protein-coding	1308
SLK	protein-coding	9748
ITPRIP-AS1	ncRNA	101927472
GSTO2	protein-coding	119391
MIR609	ncRNA	693194
ITPRIP	protein-coding	85450
GSTO1	protein-coding	9446
MIR936	ncRNA	100126326
MIR4482	ncRNA	100616323

Protein

Protein identifiers

Cilia- and flagella-associated protein 43 — Q8NDM7 (reviewed: Q8NDM7)

Alternative names: WD repeat-containing protein 96

All UniProt accessions (6): A0A0C4DFU9, Q8NDM7, H0Y4U9, H7BZT8, Q5TA04, Q5TA05

UniProt curated annotations — full annotation on UniProt →

Function. Flagellar protein involved in sperm flagellum axoneme organization and function. Involved in the regulation of the beating frequency of motile cilia on the epithelial cells of the respiratory tract.

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

Tissue specificity. Testis-specific.

Disease relevance. Spermatogenic failure 19 (SPGF19) [MIM:617592] An infertility disorder caused by spermatogenesis defects and characterized by abnormally shaped spermatozoa in the semen of affected individuals. SPGF19 patients have spermatozoa with absent, short, coiled, bent, and/or irregular-caliber flagella, which impair sperm motility. The disease is caused by variants affecting the gene represented in this entry. Hydrocephalus, normal pressure, 1 (HYDNP1) [MIM:236690] An autosomal dominant neurologic disorder characterized by a slowly progressive gait disorder, urinary incontinence, progressive intellectual decline, and ventricular enlargement on brain imaging. Cerebrospinal fluid pressure tends to be in the high normal range. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CFAP43 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8NDM7-1	1	yes
Q8NDM7-2	2
Q8NDM7-3	3
Q8NDM7-4	4
Q8NDM7-5	5

RefSeq proteins (1): NP_079421* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF25828

UniProt features (35 total): sequence variant 13, repeat 9, splice variant 6, coiled-coil region 4, sequence conflict 2, chain 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-Q8NDM7-F1	77.27	0.14

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes, Congenital malformations, Congenital malformations of the nervous system

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): flagellar centriole; nucleoplasm; cytosol; mid piece; nuclear membrane; principal piece

Antibody reliability (HPA): 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: 122 (showing top): GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_RESPIRATORY_SYSTEM_PROCESS, GOBP_MALE_GAMETE_GENERATION, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_NUCLEUS_ORGANIZATION, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_REGULATION_OF_MICROTUBULE_BASED_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_HEAD_DEVELOPMENT, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION

GO Biological Process (5): regulation of cilium beat frequency (GO:0003356), sperm axoneme assembly (GO:0007288), cilium movement (GO:0003341), cell projection organization (GO:0030030), flagellated sperm motility (GO:0030317)

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

GO Cellular Component (5): axoneme (GO:0005930), 9+2 motile cilium (GO:0097729), cytoskeleton (GO:0005856), cilium (GO:0005929), motile cilium (GO:0031514)

GO top-level categories

25 GO namespaces:

Category	Terms
regulation of cilium movement	1
developmental process involved in reproduction	1
axoneme assembly	1
sperm flagellum assembly	1
microtubule-based movement	1
cellular component organization	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
binding	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
cellular anatomical structure	1
radial spoke	1
motile cilium	1
inner dynein arm	1
outer dynein arm	1
axonemal central pair	1
axonemal doublet microtubule	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
sperm axoneme assembly	BP	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 2,923 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP43	QRICH2	Q9H0J4	814
CFAP43	CFAP251	Q8TBY9	800
CFAP43	CFAP69	A5D8W1	781
CFAP43	DNAH1	Q9P2D7	779
CFAP43	CFAP58	Q5T655	752
CFAP43	CFAP70	Q5T0N1	750
CFAP43	TTC21A	Q8NDW8	746
CFAP43	SPEF2	Q9C093	724
CFAP43	TTC29	Q8NA56	719
CFAP43	ARMC2	Q8NEN0	712
CFAP43	FSIP2	Q5CZC0	682
CFAP43	CFAP47	Q6ZTR5	660
CFAP43	CFAP65	Q6ZU64	654
CFAP43	CCDC39	Q9UFE4	626
CFAP43	CFAP91	Q7Z4T9	625

IntAct

Human interaction partners of CFAP43 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
H3-4	physical association	0.400	1

BioGRID (11 interactions; top human partners by supporting records): CIT (Affinity Capture-MS), CNNM2 (Cross-Linking-MS (XL-MS)), CUL7 (Affinity Capture-MS), HIST3H3 (Cross-Linking-MS (XL-MS)), PARP11 (Proximity Label-MS), PARP2 (Proximity Label-MS), SEC13 (Two-hybrid), TOP3B (Affinity Capture-RNA), YWHAE (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for CFAP43: 334 ClinVar records (24 pathogenic / likely pathogenic); 4 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	9
Uncertain significance	225
Likely benign	41
Benign	14

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 24 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
3893050	NM_025145.7(CFAP43):c.3749del (p.Thr1250fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2498469	NM_025145.7(CFAP43):c.3831T>G (p.Tyr1277Ter)	Pathogenic	criteria provided, single submitter	1
4850217	NM_025145.7(CFAP43):c.641dup (p.Gln216fs)	Pathogenic	criteria provided, single submitter	1
4851978	NM_025145.7(CFAP43):c.1442+1G>A	Pathogenic	criteria provided, single submitter	1
2585282	NM_025145.7(CFAP43):c.3937C>T (p.Arg1313Ter)	Likely pathogenic	criteria provided, single submitter	1
3239653	NM_025145.7(CFAP43):c.3101A>C (p.Lys1034Thr)	Likely pathogenic	criteria provided, single submitter	1
3893051	NM_025145.7(CFAP43):c.4579dup (p.Ser1527fs)	Likely pathogenic	criteria provided, single submitter	1
3893189	NM_025145.7(CFAP43):c.2758G>T (p.Glu920Ter)	Likely pathogenic	criteria provided, single submitter	1
3906976	NM_025145.7(CFAP43):c.3145C>T (p.Arg1049Ter)	Likely pathogenic	criteria provided, single submitter	1
4081241	NM_025145.7(CFAP43):c.2706_2707del (p.Val904fs)	Likely pathogenic	criteria provided, single submitter	1
4850457	NM_025145.7(CFAP43):c.1217_1220del (p.Leu406fs)	Likely pathogenic	criteria provided, single submitter	1
523145	NM_025145.7(CFAP43):c.3541-2A>C	Pathogenic	no assertion criteria provided	2
430933	NM_025145.7(CFAP43):c.2802T>A (p.Cys934Ter)	Pathogenic	no assertion criteria provided	1
430934	NM_025145.7(CFAP43):c.4132C>T (p.Arg1378Ter)	Pathogenic	no assertion criteria provided	1
430935	NM_025145.7(CFAP43):c.386C>A (p.Ser129Tyr)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CFAP43’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; 17 predictions of 4,217):

Position(s)	Effect	Δscore	Sites
10:104130312	acceptor_gain	1.0000
10:104131329–104131330	donor_loss	1.0000	4
10:104131511	acceptor_gain	1.0000
10:104131644	acceptor_gain	1.0000
10:104132198	acceptor_gain	1.0000
10:104142303	donor_gain	1.0000
10:104142311	donor_gain	1.0000
10:104143439	donor_gain	1.0000
10:104145474–104145475	donor_loss	1.0000	5
10:104146200	donor_gain	1.0000

AlphaMissense

2,056 missense substitutions predicted likely pathogenic (of 11,079 scored), across 710 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
M1124	9	0.840	0.972
M1123	9	0.785	0.967
D1356	8	0.948	0.989
F162	8	0.935	0.989
F1291	8	0.926	0.991
N907	8	0.915	0.992
F118	8	0.885	0.978
N828	8	0.884	0.948
F50	8	0.863	0.969
H679	8	0.811	0.946
D1284	8	0.792	0.954
W261	7	0.983	0.998
W1370	7	0.982	0.997
W139	7	0.978	0.996
F1310	7	0.958	0.984
W1502	7	0.949	0.989
W886	7	0.940	0.987
F1023	7	0.936	0.984
F842	7	0.928	0.984
F1027	7	0.920	0.986

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Uterine Corpus Endometrial Carcinoma)

Disease associations

OMIM: gene MIM:617558 | disease phenotypes: MIM:236690, MIM:617592

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
non-syndromic male infertility due to sperm motility disorder	Supportive	Autosomal recessive
normal pressure hydrocephalus	Limited	Autosomal dominant
spermatogenic failure 19	Limited	Autosomal recessive

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

3 validity classifications:

Disease	Classification	Inheritance
spermatogenic failure 19	Definitive	AR
primary ciliary dyskinesia	Limited	AR
normal pressure hydrocephalus	Disputed	AD

Mondo (4): normal pressure hydrocephalus (MONDO:0009366), oligospermia (MONDO:0001913), spermatogenic failure 19 (MONDO:0054723), (MONDO:0017173)

Orphanet (1): NON RARE IN EUROPE: Normal pressure hydrocephalus (Orphanet:314928)

HPO phenotypes

14 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000726	Dementia
HP:0001263	Global developmental delay
HP:0001288	Gait disturbance
HP:0002343	Normal pressure hydrocephalus
HP:0002607	Bowel incontinence
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

GWAS associations

4 associations:

Study	Trait	p-value
GCST008163_409	Height	3e-6
GCST000246_6	Attention deficit hyperactivity disorder	4e-6
GCST007637_47	Diffusing capacity of carbon monoxide	5e-6
GCST004722_8	Left ventricular obstructive tract defect (maternal effect)	9e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0009369	diffusing capacity of the lung for carbon monoxide

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D006850	Hydrocephalus, Normal Pressure	C10.228.140.602.750
D009845	Oligospermia	C12.100.500.430.508; C12.100.750.700.508; C12.200.294.430.508

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, increases mutagenesis, affects expression, decreases expression	4
sodium arsenite	decreases expression, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, affects response to substance	1
2-palmitoylglycerol	increases expression	1
licochalcone B	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
N-Nitrosopyrrolidine	decreases expression	1
Nicotine	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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

showing 60 of 354 trials:

NCT	Phase	Status	Title
NCT00793416	Phase 4	WITHDRAWN	ShuntCheck Accuracy in Detecting Shunt Obstruction Normal Pressure Hydrocephalus (NPH) Patients
NCT00029224	Phase 4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	Phase 4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	Phase 4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	Phase 4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	Phase 4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	Phase 4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	Phase 4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	Phase 4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	Phase 4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	Phase 4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	Phase 4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	Phase 4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	Phase 4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	Phase 4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	Phase 4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	Phase 4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	Phase 4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	Phase 4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	Phase 4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	Phase 4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	Phase 4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	Phase 4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	Phase 4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	Phase 4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	Phase 4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	Phase 4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	Phase 4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	Phase 4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	Phase 4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	Phase 4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	Phase 4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	Phase 4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	Phase 4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	Phase 4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	Phase 4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	Phase 4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	Phase 4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	Phase 4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	Phase 4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	Phase 4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer
NCT01673984	Phase 4	TERMINATED	GP Extended Action Triptorelin
NCT01753297	Phase 4	COMPLETED	A Study of Immediate 9 Months Adjuvant Hormone Therapy With Triptorelin 11.25 mg Versus Active Surveillance After Radical Prostatectomy in High Risk Prostate Cancer Patients.
NCT01794793	Phase 4	COMPLETED	Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in Novartis-sponsored Studies
NCT01950871	Phase 4	TERMINATED	Prostate Guided Biopsy Study Evaluating the Diagnostic Performance of Prostate HistoScanning
NCT01995513	Phase 4	COMPLETED	Safety Study of Continued Enzalutamide Treatment In Prostate Cancer Patients
NCT02102646	Phase 4	COMPLETED	MRI Substudy; Metabolic Changes Due to Iatrogenic Hypogonadism
NCT02116582	Phase 4	COMPLETED	A Study to Evaluate Enzalutamide After Abiraterone in Metastatic Castration-Resistant Prostate Cancer
NCT02149628	Phase 4	COMPLETED	The Effect of Propofol Based Total Intravenous Anesthesia on Oxidative Stress and Nitric Oxide
NCT02405858	Phase 4	COMPLETED	A Study of Abiraterone Acetate in Metastatic Castration-Resistant Prostate Cancer Participants Who Responded Poorly to the First-line Combined Androgen Blockade Therapy
NCT02441517	Phase 4	TERMINATED	A Study of Enzalutamide Re-treatment in Metastatic Castration-resistant Prostate Cancer After Docetaxel and/or Cabazitaxel Treatment
NCT02441894	Phase 4	COMPLETED	Combination of Cabazitaxel With Prednisolone With Primary Prophylaxis With PEG-G-CSF in Treatment of Patients With Prostate Cancer
NCT02475057	Phase 4	COMPLETED	Endothelial Function in Prostate Cancer Patients on Degarelix vs. Luteinizing Hormone-Releasing Hormone Agonists
NCT02511665	Phase 4	UNKNOWN	Metformin And Longevity
NCT02651948	Phase 4	COMPLETED	Transperineal, MRI-guided, Prostate Biopsy
NCT02721433	Phase 4	COMPLETED	4-weekly Versus 12-weekly Administration of Bone-targeted Agents in Patients With Bone Metastases
NCT02726009	Phase 4	COMPLETED	A Trial to Evaluate Safety of Firmagon® (Degarelix) in Indian Patients Diagnosed With Advanced Hormone-dependent Prostate Cancer
NCT02749825	Phase 4	TERMINATED	Comparison of Trelstar Versus Lupron or Zoladex in Advanced Prostate Cancer
NCT02757365	Phase 4	UNKNOWN	Efficiency Study of Aspirin to Prevent the Occurrence of Prostate Cancer
NCT02773251	Phase 4	COMPLETED	The Effect of Guardix-solution for the Prevention of Postoperative Intestinal Adhesion and Intestinal Obstruction After Laparoscopic Pelvic Cavity Surgery