CFAP74

Summary

CFAP74 (cilia and flagella associated protein 74, HGNC:29368) is a protein-coding gene on chromosome 1p36.33, encoding Cilia- and flagella-associated protein 74 (Q9C0B2). As part of the central apparatus of the cilium axoneme may play a role in cilium movement.

Predicted to be involved in axoneme assembly. Located in cytoplasm; nucleus; and sperm flagellum. Implicated in primary ciliary dyskinesia.

Source: NCBI Gene 85452 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): ciliary dyskinesia, primary, 49, without situs inversus (Moderate, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 224 total — 7 pathogenic, 7 likely-pathogenic
• GTEx eGene: eQTL in 19 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 56
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.80 (unconstrained)
• MANE Select transcript: NM_001304360
• Notable: 224 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29368
Approved symbol	CFAP74
Name	cilia and flagella associated protein 74
Location	1p36.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ45476
Ensembl gene	ENSG00000142609
Ensembl biotype	protein_coding
OMIM	620187
Entrez	85452

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 retained_intron, 4 protein_coding

MANE Select: ENST00000682832

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

ENST00000682832, ENST00000270720, ENST00000378590, ENST00000378592, ENST00000412120, ENST00000461752, ENST00000464311, ENST00000468610, ENST00000493316, ENST00000493964, ENST00001145099

RefSeq mRNA: 1 — MANE Select: NM_001304360 NM_001304360

CCDS: CCDS90840

Canonical transcript exons

ENST00000682832 — 39 exons

Exon	Start	End
ENSE00001696103	1926894	1927028
ENSE00001767669	1927607	1927746
ENSE00001833586	1942028	1942156
ENSE00001844333	1940316	1940403
ENSE00001896802	1930060	1930336
ENSE00001910630	1946317	1946439
ENSE00001924949	1928784	1928882
ENSE00001931348	1939594	1939767
ENSE00001958120	1938855	1938988
ENSE00001958749	1944331	1944452
ENSE00003473372	1959964	1960030
ENSE00003476387	1963749	1963867
ENSE00003478389	1926457	1926512
ENSE00003514677	1988512	1988655
ENSE00003522881	1925783	1925938
ENSE00003528963	1926652	1926761
ENSE00003536274	1923367	1923499
ENSE00003552917	1966371	1966526
ENSE00003561944	1955691	1955850
ENSE00003585076	1988889	1988973
ENSE00003605108	1990890	1990975
ENSE00003622276	1924391	1924520
ENSE00003634604	1923775	1923929
ENSE00003650472	1926228	1926347
ENSE00003664478	1959120	1959209
ENSE00003686348	1964888	1965061
ENSE00003691473	1956620	1956784
ENSE00003714108	1972937	1973047
ENSE00003720442	1985386	1985490
ENSE00003722823	1971980	1972082
ENSE00003730804	1986937	1987035
ENSE00003736758	1974025	1974198
ENSE00003744170	1968635	1968833
ENSE00003745188	1970659	1970816
ENSE00003749889	1946990	1947054
ENSE00003824989	1922589	1922723
ENSE00003916243	1921957	1922388
ENSE00003920541	2003701	2003786
ENSE00003924366	1922985	1923145

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 96.92.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2313 / max 36.0868, expressed in 109 samples.

Highest expression (Bgee): uterine tube, epithelium of bronchus, bronchial epithelial cell, bronchus, olfactory segment of nasal mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CFAP74 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 19 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

20 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	6.4e-25	-0.32	1:1985619:A:G
Brain Cortex	eqtl	1.0e-16	+0.52	1:1931587:A:G
Brain Frontal Cortex BA9	eqtl	2.4e-16	-0.47	1:1924659:C:T
Testis	sqtl	8.0e-15	-0.86	1:1976646:A:G
Liver	eqtl	6.6e-12	+0.53	1:1947645:C:T
Brain Anterior cingulate cortex BA24	eqtl	4.0e-10	-0.44	1:1966606:G:A
Pituitary	eqtl	6.9e-10	-0.42	1:1989523:T:C
Brain Nucleus accumbens basal ganglia	eqtl	1.4e-07	-0.33	1:1937046:G:A
Skin Sun Exposed Lower leg	eqtl	6.5e-07	-0.32	1:1976644:G:A
Brain Cerebellar Hemisphere	eqtl	2.3e-06	-0.56	1:1957243:T:C
Spleen	eqtl	6.6e-06	+0.51	1:1924659:C:T
Brain Putamen basal ganglia	eqtl	7.4e-05	+0.22	1:1797530:C:A
Brain Caudate basal ganglia	eqtl	3.1e-04	-0.20	1:1942186:G:A
Brain Cerebellum	eqtl	1.7e-03	-0.56	1:1959595:C:T
Brain Hypothalamus	eqtl	3.2e-03	+0.17	1:1810077:T:A
Brain Amygdala	eqtl	4.7e-03	-0.34	1:1844830:C:A
Thyroid	eqtl	1.2e-02	+0.25	1:1956754:C:A
Brain Substantia nigra	eqtl	1.4e-02	+0.35	1:2319680:A:G
Adrenal Gland	eqtl	3.0e-02	+0.29	1:1947645:C:T
Lung	eqtl	4.0e-02	-0.27	1:2458272:G:A

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
9861	0.0909	46
9863	0.0488	21
9859	0.0339	13
9864	0.0289	7
9862	0.0288	12

Top tissues by expression

showing 100 of 279 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	96.92	gold quality
epithelium of bronchus	UBERON:0002031	85.64	gold quality
bronchial epithelial cell	CL:0002328	85.31	gold quality
bronchus	UBERON:0002185	84.54	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.41	gold quality
right testis	UBERON:0004534	82.88	gold quality
left testis	UBERON:0004533	82.81	gold quality
cerebellar hemisphere	UBERON:0002245	82.43	gold quality
cerebellar cortex	UBERON:0002129	82.16	gold quality
cerebellum	UBERON:0002037	80.16	gold quality
testis	UBERON:0000473	79.90	gold quality
hair follicle	UBERON:0002073	79.66	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.99	gold quality
buccal mucosa cell	CL:0002336	78.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.44	gold quality
right frontal lobe	UBERON:0002810	75.47	gold quality
mucosa of paranasal sinus	UBERON:0005030	74.86	silver quality
tibialis anterior	UBERON:0001385	73.36	silver quality
Brodmann (1909) area 9	UBERON:0013540	72.25	gold quality
nasal cavity mucosa	UBERON:0001826	72.04	gold quality
anterior cingulate cortex	UBERON:0009835	71.95	gold quality
cingulate cortex	UBERON:0003027	71.93	gold quality
caudate nucleus	UBERON:0001873	71.83	gold quality
right lung	UBERON:0002167	71.58	gold quality
prefrontal cortex	UBERON:0000451	71.50	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	71.50	gold quality
right lobe of liver	UBERON:0001114	71.07	gold quality
frontal cortex	UBERON:0001870	70.70	gold quality
nasal cavity epithelium	UBERON:0005384	70.07	gold quality
nucleus accumbens	UBERON:0001882	69.98	gold quality
neocortex	UBERON:0001950	69.93	gold quality
parotid gland	UBERON:0001831	68.92	gold quality
epithelial cell of pancreas	CL:0000083	68.81	gold quality
cerebral cortex	UBERON:0000956	68.66	gold quality
fallopian tube	UBERON:0003889	68.61	gold quality
telencephalon	UBERON:0001893	68.38	gold quality
brain	UBERON:0000955	68.37	gold quality
putamen	UBERON:0001874	68.27	gold quality
deltoid	UBERON:0001476	67.82	gold quality
forebrain	UBERON:0001890	67.73	gold quality
epithelium of nasopharynx	UBERON:0001951	67.73	gold quality
pancreatic ductal cell	CL:0002079	66.94	silver quality
left adrenal gland	UBERON:0001234	66.55	gold quality
gingival epithelium	UBERON:0001949	66.55	gold quality
superficial temporal artery	UBERON:0001614	66.41	gold quality
left adrenal gland cortex	UBERON:0035825	66.27	gold quality
hypothalamus	UBERON:0001898	66.15	gold quality
gingiva	UBERON:0001828	66.07	gold quality
ileal mucosa	UBERON:0000331	66.02	silver quality
amygdala	UBERON:0001876	65.83	gold quality
olfactory bulb	UBERON:0002264	65.41	gold quality
type B pancreatic cell	CL:0000169	65.31	gold quality
Ammon’s horn	UBERON:0001954	65.27	gold quality
right adrenal gland cortex	UBERON:0035827	65.15	gold quality
adrenal cortex	UBERON:0001235	65.12	gold quality
adenohypophysis	UBERON:0002196	64.80	gold quality
right adrenal gland	UBERON:0001233	64.78	gold quality
primary visual cortex	UBERON:0002436	64.77	gold quality
left uterine tube	UBERON:0001303	64.59	gold quality
adrenal gland	UBERON:0002369	64.58	gold quality
oviduct epithelium	UBERON:0004804	64.08	silver quality
epithelium of esophagus	UBERON:0001976	63.95	gold quality
temporal lobe	UBERON:0001871	63.75	gold quality
superior frontal gyrus	UBERON:0002661	63.71	gold quality
esophagus squamous epithelium	UBERON:0006920	63.57	gold quality
pituitary gland	UBERON:0000007	63.43	gold quality
upper leg skin	UBERON:0004262	63.35	silver quality
heart right ventricle	UBERON:0002080	63.29	gold quality
squamous epithelium	UBERON:0006914	62.79	gold quality
occipital lobe	UBERON:0002021	62.76	gold quality
male germ cell	CL:0000015	62.65	gold quality
postcentral gyrus	UBERON:0002581	62.25	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	62.11	gold quality
caput epididymis	UBERON:0004358	62.07	gold quality
sperm	CL:0000019	62.01	gold quality
diaphragm	UBERON:0001103	61.85	gold quality
upper lobe of left lung	UBERON:0008952	61.78	gold quality
adrenal tissue	UBERON:0018303	61.78	gold quality
upper lobe of lung	UBERON:0008948	61.53	gold quality
parietal lobe	UBERON:0001872	61.39	silver quality
lateral globus pallidus	UBERON:0002476	61.30	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	60.97	gold quality
inferior olivary complex	UBERON:0002127	60.91	gold quality
Brodmann (1909) area 23	UBERON:0013554	60.83	gold quality
lung	UBERON:0002048	60.82	gold quality
Brodmann (1909) area 46	UBERON:0006483	60.45	gold quality
endocervix	UBERON:0000458	60.17	gold quality
tongue squamous epithelium	UBERON:0006919	60.06	gold quality
liver	UBERON:0002107	59.63	gold quality
quadriceps femoris	UBERON:0001377	59.59	gold quality
corpus callosum	UBERON:0002336	59.45	gold quality
substantia nigra	UBERON:0002038	59.35	gold quality
colonic mucosa	UBERON:0000317	59.32	gold quality
middle temporal gyrus	UBERON:0002771	59.29	gold quality
mucosa of sigmoid colon	UBERON:0004993	59.23	gold quality
stromal cell of endometrium	CL:0002255	58.84	gold quality
midbrain	UBERON:0001891	58.73	gold quality
vastus lateralis	UBERON:0001379	58.52	gold quality
lower esophagus mucosa	UBERON:0035834	58.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.53
E-MTAB-6678	no	3.97

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 73 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	17.1	medium
Frontal cortex	tissue	11.2
Postcentral gyrus	tissue	10.3
Nucleus accumbens	tissue	9.2
Hippocampus	tissue	8.4	not detected
Locus coeruleus	tissue	7.3
Caudate putamen	tissue	7.0
Fallopian tube	tissue	6.5	low
Periaqueductal gray	tissue	5.8
Cerebellum	tissue	5.4	not detected
Testis	tissue	4.8	high
Basal ganglia	tissue	3.8	not detected
Hypothalamus	tissue	3.8
Olfactory bulb	tissue	3.2
Septum	tissue	3.1
Amygdala	tissue	3.0
Skin 1	tissue	2.9	not detected
Hippocampal formation	tissue	2.8
Cerebral cortex	tissue	2.7	not detected
Ventral forebrain	tissue	2.7
Insular cortex	tissue	2.7
Putamen	tissue	2.4
Pons	tissue	2.2
Entorhinal cortex	tissue	2.1
Temporal cortex	tissue	2.1
Retrosplenial cortex	tissue	2.0
Prefrontal cortex	tissue	1.9
Midbrain	tissue	1.9
Somatosensory cortex	tissue	1.9
Thalamus	tissue	1.8
Retrosplenial and cingulate cortex	tissue	1.8
Motor cortex	tissue	1.7
Medulla oblongata	tissue	1.6
Superior colliculi	tissue	1.6
Corpus callosum	tissue	1.6
Occipital cortex	tissue	1.6
Lung	tissue	1.3	not detected
Adrenal gland	tissue	1.2	not detected
Substantia nigra	tissue	1.1
Thyroid gland	tissue	1.0	not detected
Esophagus	tissue	0.9	not detected
Spinal cord	tissue	0.9
Bone marrow	tissue	0.9	not detected
Skeletal muscle	tissue	0.8	not detected
Retina	tissue	0.7
Gallbladder	tissue	0.7	not detected
Lymph node	tissue	0.6	not detected
Endometrium 1	tissue	0.5	low
Liver	tissue	0.4	not detected
Pituitary gland	tissue	0.3
Seminal vesicle	tissue	0.3	not detected
Salivary gland	tissue	0.3	not detected
Placenta	tissue	0.3	not detected
Appendix	tissue	0.3	not detected
Breast	tissue	0.2	not detected
Stomach 1	tissue	0.2	not detected
Heart muscle	tissue	0.2	not detected
Adipose tissue	tissue	0.2	not detected
Rectum	tissue	0.2	not detected
Colon	tissue	0.2	not detected

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Periaquaductal grey, lateral (15.2), Flocculonodular lobe (14.6), Parieto-temporal junction (white matter) (14.1), Temporal white matter (13.9), Vermis (13.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CFAP74 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

18 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-6069	97.45	65.88	357
HSA-MIR-3126-3P	97.17	66.51	468
HSA-MIR-3907	96.76	65.04	662

Functional genomics

gnomAD constraint: pLI 6.94e-26, LOEUF 0.799, missense Z -0.061 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000682832 — one region, missense o/e 1.02.

Literature-anchored findings (GeneRIF, showing 3)

• KIAA1751 is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• Biallelic mutations of CFAP74 may cause human primary ciliary dyskinesia and MMAF phenotype. (PMID:32555313)
• Recessive Mutations in CFAP74 Cause Primary Ciliary Dyskinesia with Normal Ciliary Ultrastructure. (PMID:36047773)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cfap74	ENSDARG00000075917
mus_musculus	Cfap74	ENSMUSG00000078490
rattus_norvegicus	Cfap74	ENSRNOG00000023627

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
GABRD	protein-coding	2563
TMEM52	protein-coding	339456
CALML6	protein-coding	163688
PRKCZ-DT	ncRNA	105378591
PRKCZ	protein-coding	5590
GNB1-DT	ncRNA	105378949

Protein

Protein identifiers

Cilia- and flagella-associated protein 74 — Q9C0B2 (reviewed: Q9C0B2)

All UniProt accessions (3): A0A804HLA9, Q5T2D8, Q9C0B2

UniProt curated annotations — full annotation on UniProt →

Function. As part of the central apparatus of the cilium axoneme may play a role in cilium movement. May play an important role in sperm architecture and function.

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

Disease relevance. Ciliary dyskinesia, primary, 49, without situs inversus (CILD49) [MIM:620197] A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD49 is an autosomal recessive form without situs abnormalities. Affected males also show infertility due to defective flagellar morphology and function. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CFAP74 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9C0B2-1	1	yes
Q9C0B2-2	2
Q9C0B2-3	3

RefSeq proteins (1): NP_001291289* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013783	Ig-like_fold	Homologous_superfamily
IPR056306	Ig-CFAP74_2nd	Domain
IPR056307	Ig-CFAP74_3rd	Domain
IPR056310	Ig-CFAP74_4th	Domain
IPR059255	Ig_CFAP74_1st	Domain

Pfam: PF24770, PF24771, PF24778, PF24798

UniProt features (18 total): sequence variant 7, sequence conflict 3, splice variant 3, compositionally biased region 2, chain 1, region of interest 1, coiled-coil region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C0B2-F1	69.38	0.08

Human Protein Atlas

Protein class: Predicted intracellular proteins, Human disease related genes, UniProt - Evidence at transcript level

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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: 173 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GOBP_CILIUM_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_AXONEME_ASSEMBLY, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM, GOCC_CILIUM, DODD_NASOPHARYNGEAL_CARCINOMA_DN, chr1p36, LU_EZH2_TARGETS_DN, GOBP_MICROTUBULE_CYTOSKELETON_ORGANIZATION, GOCC_9PLUS2_MOTILE_CILIUM, BCAT.100_UP.V1_UP

GO Biological Process (1): axoneme assembly (GO:0035082)

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

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), axoneme (GO:0005930), sperm flagellum (GO:0036126)

GO top-level categories

11 GO namespaces:

Category	Terms
cellular anatomical structure	2
microtubule bundle formation	1
cellular component assembly	1
cilium assembly	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
9+2 motile cilium	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 6 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
cytoplasm	CC	mutant phenotype
nucleus	CC	mutant phenotype
sperm flagellum	CC	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 905 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP74	GABRD	O14764	816
CFAP74	SPEF2	Q9C093	715
CFAP74	TMEM52	Q8NDY8	702
CFAP74	PRKCZ	Q05513	612
CFAP74	CCDC39	Q9UFE4	572
CFAP74	DRC1	Q96MC2	570
CFAP74	CCDC40	Q4G0X9	564
CFAP74	ODAD2	Q5T2S8	557
CFAP74	RSPH10B	P0C881	554
CFAP74	SLC6A1	P30531	553
CFAP74	GABRA5	P31644	547
CFAP74	MORN1	Q5T089	539
CFAP74	DNAH1	Q9P2D7	525
CFAP74	CFAP43	Q8NDM7	521
CFAP74	CFAP70	Q5T0N1	520

IntAct

Human interaction partners of CFAP74 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
C20orf96	physical association	0.560	1
MANF	physical association	0.400	1
SPTB	physical association	0.400	1
STT3B	physical association	0.400	1
HCN4	association	0.350	1
UNC119B	association	0.350	1

BioGRID (14 interactions; top human partners by supporting records): APEX1 (Affinity Capture-MS; 2 records), HTR1E (Affinity Capture-MS; 2 records), C20orf96 (Affinity Capture-MS), CUL3 (Affinity Capture-MS), DDX39A (Affinity Capture-RNA), FAM189B (Affinity Capture-MS), FIS1 (Affinity Capture-MS), GNS (Cross-Linking-MS (XL-MS)), LMNA (Cross-Linking-MS (XL-MS)), PARP9 (Proximity Label-MS), RELA (Affinity Capture-MS), SCNN1D (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for CFAP74: 224 ClinVar records (14 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	7
Uncertain significance	159
Likely benign	38
Benign	3

Top pathogenic / likely-pathogenic (14)

Showing all 14 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
3340495	NM_001304360.2(CFAP74):c.2924del (p.Leu975fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2443737	NM_001304360.2(CFAP74):c.1706dup (p.Gly570fs)	Likely pathogenic	criteria provided, single submitter	2
3340496	NM_001304360.2(CFAP74):c.1714_1715del (p.Leu572fs)	Likely pathogenic	criteria provided, single submitter	1
4280102	NM_001304360.2(CFAP74):c.838C>T (p.Arg280Ter)	Likely pathogenic	criteria provided, single submitter	1
4850121	NM_001304360.2(CFAP74):c.832_833del (p.Met278fs)	Likely pathogenic	criteria provided, single submitter	1
2443731	NM_001304360.2(CFAP74):c.983G>A (p.Gly328Asp)	Pathogenic	no assertion criteria provided	1
2443732	NM_001304360.2(CFAP74):c.3532G>A (p.Asp1178Asn)	Pathogenic	no assertion criteria provided	1
2443733	NM_001304360.2(CFAP74):c.652C>T (p.Arg218Trp)	Pathogenic	no assertion criteria provided	1
2443734	NM_001304360.2(CFAP74):c.4331G>C (p.Ser1444Thr)	Pathogenic	no assertion criteria provided	1
2443736	NM_001304360.2(CFAP74):c.907del (p.Gln303fs)	Pathogenic	no assertion criteria provided	1
3362881	NM_001304360.2(CFAP74):c.3044T>C (p.Val1015Ala)	Likely pathogenic	no assertion criteria provided	1
3362882	NM_001304360.2(CFAP74):c.2452C>T (p.Arg818Trp)	Likely pathogenic	no assertion criteria provided	1
427642	GRCh37/hg19 1p36.33-36.32(chr1:852863-4203509)x3	Pathogenic	no assertion criteria provided	1
1340028	GRCh37/hg19 1p36.33-36.13(chr1:849466-17525065)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CFAP74’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; 30 predictions of 4,626):

Position(s)	Effect	Δscore	Sites
1:1923931	acceptor_loss	1.0000
1:1924492	acceptor_gain	1.0000
1:1924521–1924522	acceptor_loss	1.0000	6
1:1926643	donor_gain	1.0000
1:1927606	donor_loss	1.0000
1:1938853–1938854	donor_loss	1.0000	5
1:1940491	donor_gain	1.0000
1:1946315–1946316	donor_loss	1.0000	4
1:1946440–1946441	acceptor_loss	1.0000	6
1:1955689–1955690	donor_loss	1.0000	4

AlphaMissense

1,613 missense substitutions predicted likely pathogenic (of 10,731 scored), across 540 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
F1422	8	0.941	0.992
F1443	8	0.938	0.991
F869	8	0.934	0.996
F954	8	0.934	0.993
F927	8	0.923	0.974
N944	8	0.920	0.995
F1028	8	0.896	0.977
N1371	8	0.896	0.971
N1269	8	0.895	0.981
F524	8	0.890	0.981
F1073	8	0.888	0.984
F584	8	0.886	0.979
F1006	8	0.886	0.982
F1075	8	0.886	0.989
F1288	8	0.881	0.978
F515	8	0.864	0.967
N1415	8	0.862	0.955
F969	8	0.859	0.976
F994	8	0.850	0.966
D1454	8	0.849	0.953

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Squamous Cell Carcinoma (validation)	favorable	0.000517

Disease associations

OMIM: gene MIM:620187 | disease phenotypes: MIM:620197

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
ciliary dyskinesia, primary, 49, without situs inversus	Limited	Autosomal recessive

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
ciliary dyskinesia, primary, 49, without situs inversus	Moderate	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
Respiratory ciliopathies including non-CF bronchiectasis	green

Mondo (1): ciliary dyskinesia, primary, 49, without situs inversus (MONDO:0859353)

HPO phenotypes

56 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000119	Abnormality of the genitourinary system
HP:0000238	Hydrocephalus
HP:0000365	Hearing impairment
HP:0000389	Chronic otitis media
HP:0000403	Recurrent otitis media
HP:0000405	Conductive hearing impairment
HP:0000510	Rod-cone dystrophy
HP:0000750	Delayed speech and language development
HP:0000924	Abnormality of the skeletal system
HP:0001217	Clubbing
HP:0001627	Abnormal heart morphology
HP:0001669	Transposition of the great arteries
HP:0001696	Situs inversus totalis
HP:0001719	Double outlet right ventricle
HP:0001742	Nasal congestion
HP:0001746	Asplenia
HP:0001748	Polysplenia
HP:0002011	Morphological central nervous system abnormality
HP:0002110	Bronchiectasis
HP:0002119	Ventriculomegaly
HP:0002205	Recurrent respiratory infections
HP:0002257	Chronic rhinitis
HP:0002566	Intestinal malrotation
HP:0002643	Neonatal respiratory distress
HP:0002878	Respiratory failure
HP:0003251	Male infertility
HP:0005301	Persistent left superior vena cava
HP:0005425	Recurrent sinopulmonary infections
HP:0006536	Airway obstruction
HP:0008222	Female infertility
HP:0010772	Anomalous pulmonary venous return
HP:0011108	Recurrent sinusitis
HP:0011109	Chronic sinusitis
HP:0011274	Recurrent mycobacterial infections
HP:0011463	Childhood onset
HP:0011535	Abnormal atrial arrangement
HP:0011539	Atrial situs ambiguous
HP:0011617	Pulmonary situs ambiguus
HP:0011947	Respiratory tract infection
HP:0012206	Abnormal sperm motility
HP:0012265	Ciliary dyskinesia
HP:0025177	Peribronchovascular interstitial thickening
HP:0025576	Abnormal inferior vena cava morphology
HP:0030680	Abnormal cardiovascular system morphology
HP:0030828	Wheezing
HP:0031245	Productive cough
HP:0031456	Ectopic pregnancy
HP:0032016	Abnormal sputum
HP:0032543	Lithoptysis
HP:0032559	Short sperm flagella
HP:0032560	Coiled sperm flagella
HP:0033036	Decreased nasal nitric oxide
HP:0034315	Chronic cough
HP:0100582	Nasal polyposis
HP:0100750	Atelectasis

GWAS associations

1 associations:

Study	Trait	p-value
GCST003123_1	Severe influenza A (H1N1) infection	8e-10

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
dicrotophos	increases expression	1
propionaldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	affects methylation, increases methylation	1
coumarin	decreases phosphorylation	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Fulvestrant	increases methylation	1
Arsenic	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Methapyrilene	increases methylation	1
Quercetin	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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

showing 60 of 198 trials:

NCT	Phase	Status	Title
NCT00331656	Phase 4	UNKNOWN	Comparative Study of Non-Invasive Mask Ventilation vs Cuirass Ventilation in Patients With Acute Respiratory Failure.
NCT00994552	Phase 4	UNKNOWN	Comparison of Pressure Support and Pressure Control Ventilation in Chronic Respiratory Failure
NCT00839033	Phase 3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00942227	Phase 3	COMPLETED	The Value of Traction in Treatment of Lumbar Radiculopathy
NCT00979108	Phase 3	COMPLETED	The Value of Traction in the Treatment of Cervical Radiculopathy
NCT01826487	Phase 3	COMPLETED	Phase 3 Study of Ataluren in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)
NCT02090959	Phase 3	TERMINATED	An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy
NCT02436096	Phase 3	COMPLETED	A Study to Evaluate eFFIcacy and Safety of Sublingual TNX-102 SL Tablet Taken at Bedtime in Patients With fibRoMyalgia
NCT02829814	Phase 3	TERMINATED	Repeat of: A Study to Evaluate Efficacy and Safety of Sublingual TNX-102 SL Tablet Taken at Bedtime in Patients With Fibromyalgia
NCT03179631	Phase 3	COMPLETED	Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy
NCT05126758	Phase 3	ACTIVE_NOT_RECRUITING	A Study of Deramiocel (CAP-1002) in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT05156320	Phase 3	COMPLETED	Efficacy and Safety of Apitegromab in Patients With Later-Onset Spinal Muscular Atrophy Treated With Nusinersen or Risdiplam
NCT05337553	Phase 3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy
NCT05626855	Phase 3	ACTIVE_NOT_RECRUITING	Long-Term Safety & Efficacy of Apitegromab in Patients With SMA Who Completed Previous Trials of Apitegromab
NCT06672237	Phase 3	RECRUITING	A Phase 3 Study of NTLA-2001 in ATTRv-PN
NCT01074359	Phase 2	TERMINATED	Safety and Efficacy Study of A0001 in Patients With the A3243G Mitochondrial DNA Point Mutation
NCT01371149	Phase 2	COMPLETED	Patient -Ventilator Interaction in Chronic Respiratory Failure
NCT02022072	Phase 2	TERMINATED	Evaluation of Vital Capacity
NCT03127514	Phase 2	COMPLETED	AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT03406780	Phase 2	COMPLETED	A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT03921528	Phase 2	COMPLETED	An Active Treatment Study of SRK-015 in Patients With Type 2 or Type 3 Spinal Muscular Atrophy
NCT05479981	Phase 2	COMPLETED	Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT06339580	Phase 2	RECRUITING	Assessment of Volume-targeted Ventilation in Patients With Neuromuscular Disease
NCT07071935	Phase 2	RECRUITING	A Clinical Trial of Early Ventilation in Amyotrophic Lateral Sclerosis (EVENT ALS)
NCT07287189	Phase 2	RECRUITING	Phase 2 Study of SAT-3247 in Pediatric Ambulatory Patients
NCT00252252	Phase 1	COMPLETED	AutoVPAP Versus VPAP; Assessment of Sleep and Ventilation
NCT01560741	Phase 1	UNKNOWN	Telemedicine and Ventilator Titration in Chronic Respiratory Patients Initiating Non-invasive Ventilation
NCT01621984	Phase 1	COMPLETED	Therapeutic Riding and Neuromuscular Disease
NCT01758510	Phase 1	COMPLETED	Safety Study of HLA-haplo Matched Allogenic Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis
NCT03440034	Phase 1	COMPLETED	Study of Pioglitazone in Sporadic Inclusion Body Myositis
NCT05730842	Phase 1	COMPLETED	Absorption, Metabolism, Excretion and Absolute Bioavailability of EDG-5506 in Healthy Volunteers
NCT03272802	Phase 2/3	UNKNOWN	Treatment Effect of Edaravone in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00860951	Phase 1/2	COMPLETED	P300 Brain Computer Interface Keyboard to Operate Assistive Technology
NCT02362425	Phase 1/2	COMPLETED	Antioxidant Therapy in RYR1-Related Congenital Myopathy
NCT00001201	Not specified	COMPLETED	Evaluation of Neuromuscular Disease
NCT00002044	Not specified	COMPLETED	A Pilot Study To Evaluate the Effect of Retrovir (Zidovudine: AZT) in the Treatment of Human Immunodeficiency Virus (HIV) Associated Dementia and Neuromuscular Diseases
NCT00004553	Not specified	COMPLETED	Electromyography to Diagnose Neuromuscular Disorders
NCT00015470	Not specified	COMPLETED	Diagnostic Evaluation of Patients With Neuromuscular Disease
NCT00017745	Not specified	COMPLETED	Phenotype/Genotype Correlations in Neuromuscular Disorders
NCT00695591	Not specified	COMPLETED	Home Sleep Testing in Neuromuscular Disease Patients
NCT00720161	Not specified	COMPLETED	Metformin in Children With Motor Deficit
NCT00901485	Not specified	COMPLETED	Autotitrating Versus Standard Non-invasive Ventilation (NIV) in Newly Diagnosed Patients
NCT01022931	Not specified	COMPLETED	Epidemiology and Clinical Presentation of H1N1 Infection in Children in Geneva
NCT01166022	Not specified	COMPLETED	Clinical Trial of Exercise in Patients With Spinal Muscular Atrophy (SMA)
NCT01174316	Not specified	WITHDRAWN	Autotitrating Versus Standard Non-invasive Ventilation (NIV) in Acute Exacerbation of Respiratory Failure
NCT01313325	Not specified	COMPLETED	Hippotherapy to Improve the Balance of Children With Movement Disorders
NCT01372072	Not specified	COMPLETED	A Study to Investigate the Effects of Heated Humidification During Non-Invasive Ventilation
NCT01495390	Not specified	COMPLETED	A Longitudinal Study of Amyotrophic Lateral Sclerosis (ALS) Biomarkers
NCT01518439	Not specified	COMPLETED	Instrumental and Manual Increase of Couch in Neuromuscular Patients
NCT01555905	Not specified	TERMINATED	Respiratory Muscle Strength in Patients With NMD
NCT01611597	Not specified	COMPLETED	Continuous Measurement of the Activity for Clinical Evaluation at Home, for Non-ambulant Neuromuscular Patients
NCT01644162	Not specified	COMPLETED	Ventilator Monitoring in Early Exacerbation Detection
NCT01900132	Not specified	RECRUITING	Electrical Impedance Myography: Natural History Studies inNeuromuscular Disorders and Healthy Volunteers
NCT02007213	Not specified	TERMINATED	Development of a Proxy Motor Outcome Measure in Young Children With Neuromuscular Disease
NCT02068911	Not specified	COMPLETED	Concordance Between ETCO2, PTCO2 and PaCO2 in the Home-ventilated Neuromuscular Patient
NCT02078050	Not specified	TERMINATED	Volontary Inspiratory Muscles Measures Compared With Phrenic Nerves Magnetic Stimulations Measures
NCT02097368	Not specified	UNKNOWN	Bulbar Function in Neuromuscular Patients
NCT02103790	Not specified	UNKNOWN	Installation of Non-invasive Ventilation at Home Using Telemedicine : a Pilot Study on Feasibility and Impact on Ventilation Compliance
NCT02137304	Not specified	COMPLETED	A Method to Optimize Mecanical In-exsufflation in Neuromuscular Diseases
NCT02153970	Not specified	COMPLETED	Calibration and Validation of the PROMIS and Neuro-QOL Questionnaires in Cerebral Palsy and Congenital Muscular Dystrophy