CFAP221

Summary

CFAP221 (cilia and flagella associated protein 221, HGNC:33720) is a protein-coding gene on chromosome 2q14.2, encoding Cilia- and flagella-associated protein 221 (Q4G0U5). May play a role in cilium morphogenesis and ciliary function.

Predicted to enable calmodulin binding activity. Involved in cilium assembly. Located in ciliary tip; cytoskeleton; and sperm head-tail coupling apparatus.

Source: NCBI Gene 200373 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): primary ciliary dyskinesia (Definitive, ClinGen)
• GWAS associations: 2
• Clinical variants (ClinVar): 43 total — 5 pathogenic, 2 likely-pathogenic
• GTEx eGene: eQTL in 13 tissues, sQTL in 8 (q < 0.05)
• Phenotypes (HPO): 51
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.10 (unconstrained)
• MANE Select transcript: NM_001271049

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33720
Approved symbol	CFAP221
Name	cilia and flagella associated protein 221
Location	2q14.2
Locus type	gene with protein product
Status	Approved
Aliases	FAP221, PCDP1
Ensembl gene	ENSG00000163075
Ensembl biotype	protein_coding
OMIM	618704
Entrez	200373

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 23 protein_coding, 10 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 2 retained_intron

MANE Select: ENST00000413369

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 5, TSL 4: 1, TSL 5: 10

ENST00000413369, ENST00000295220, ENST00000413057, ENST00000434869, ENST00000442513, ENST00000443972, ENST00000463985, ENST00000464578, ENST00000475569, ENST00000488358, ENST00000594033, ENST00000594141, ENST00000594371, ENST00000597189, ENST00000598644, ENST00000599827, ENST00000600951, ENST00000881829, ENST00000881830, ENST00000881831, ENST00000955800, ENST00000955801, ENST00000992988, ENST00001033368, ENST00001093074, ENST00001109699, ENST00001109700, ENST00001112331, ENST00001112332, ENST00001112333, ENST00001112334, ENST00001125207, ENST00001125208, ENST00001125209, ENST00001125210, ENST00001126326, ENST00001139684

RefSeq mRNA: 1 — MANE Select: NM_001271049 NM_001271049

CCDS: CCDS33282

Canonical transcript exons

ENST00000413369 — 24 exons

Exon	Start	End
ENSE00001785570	119544449	119544510
ENSE00003458459	119587119	119587222
ENSE00003460650	119615611	119615709
ENSE00003463803	119611653	119611742
ENSE00003465259	119656362	119656661
ENSE00003474788	119546085	119546270
ENSE00003479469	119559928	119560026
ENSE00003503533	119651974	119652069
ENSE00003508686	119638259	119638417
ENSE00003526341	119646958	119647050
ENSE00003541432	119630570	119630677
ENSE00003549331	119605181	119605289
ENSE00003570740	119604876	119604987
ENSE00003572484	119625583	119625688
ENSE00003590319	119559689	119559775
ENSE00003592420	119601218	119601377
ENSE00003599903	119608502	119608589
ENSE00003602368	119604672	119604792
ENSE00003607243	119639781	119639872
ENSE00003608936	119630767	119630901
ENSE00003639186	119629875	119629955
ENSE00003640617	119549085	119549185
ENSE00003692056	119627653	119627786
ENSE00003789500	119562014	119562114

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 98.30.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4449 / max 83.9018, expressed in 334 samples.

Highest expression (Bgee): uterine tube, sperm, bronchial epithelial cell, metanephros cortex, bronchus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CFAP221 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 13 tissues and its splicing (sQTL) in 8 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 21 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Pancreas	eqtl	2.8e-33	-0.67	2:119534673:A:G
Thyroid	sqtl	9.1e-21	+0.76	2:119680939:G:C
Testis	sqtl	8.6e-13	-0.75	2:119673698:C:T
Thyroid	eqtl	6.5e-09	-0.18	2:119537417:A:G
Stomach	sqtl	3.9e-07	+0.74	2:119659211:C:T
Brain Frontal Cortex BA9	eqtl	1.9e-05	-0.29	2:119610485:A:G
Lung	sqtl	3.1e-05	-0.53	2:119681654:C:G
Brain Cortex	eqtl	8.6e-04	-0.20	2:119534673:A:G
Pancreas	sqtl	1.2e-03	+0.61	2:119673698:C:T
Pituitary	sqtl	1.5e-02	-0.55	2:119662575:G:A
Brain Putamen basal ganglia	eqtl	1.7e-02	-0.21	2:119536006:G:A
Brain Nucleus accumbens basal ganglia	eqtl	1.9e-02	-0.88	2:119274301:A:G
Brain Caudate basal ganglia	sqtl	2.0e-02	-0.60	2:119675061:C:T
Pituitary	eqtl	2.0e-02	-0.16	2:119561327:T:C
Brain Cerebellum	eqtl	2.1e-02	-0.30	2:119527792:G:A
Breast Mammary Tissue	eqtl	2.6e-02	-0.53	2:118932766:T:C
Lung	eqtl	2.8e-02	-0.07	2:119540774:A:T
Brain Caudate basal ganglia	eqtl	3.0e-02	-0.36	2:118650302:C:T
Brain Anterior cingulate cortex BA24	eqtl	3.9e-02	-0.17	2:119540774:A:T
Adipose Subcutaneous	eqtl	4.2e-02	+0.76	2:120530689:A:G

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
22275	1.2073	309
22276	0.1443	90
22277	0.0770	38
22278	0.0163	4

Top tissues by expression

showing 100 of 250 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.30	gold quality
sperm	CL:0000019	98.11	gold quality
bronchial epithelial cell	CL:0002328	93.87	gold quality
metanephros cortex	UBERON:0010533	92.78	gold quality
bronchus	UBERON:0002185	92.65	gold quality
right testis	UBERON:0004534	92.19	gold quality
left testis	UBERON:0004533	92.18	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.47	gold quality
testis	UBERON:0000473	89.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.65	gold quality
oviduct epithelium	UBERON:0004804	88.27	gold quality
epithelial cell of pancreas	CL:0000083	88.02	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.65	gold quality
body of pancreas	UBERON:0001150	87.56	gold quality
tibialis anterior	UBERON:0001385	85.45	gold quality
pancreas	UBERON:0001264	85.37	gold quality
fallopian tube	UBERON:0003889	83.70	gold quality
metanephros	UBERON:0000081	83.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.21	gold quality
adult mammalian kidney	UBERON:0000082	83.13	gold quality
islet of Langerhans	UBERON:0000006	82.82	gold quality
pancreatic ductal cell	CL:0002079	82.45	silver quality
right frontal lobe	UBERON:0002810	82.38	gold quality
right lung	UBERON:0002167	81.86	gold quality
prefrontal cortex	UBERON:0000451	80.76	gold quality
adenohypophysis	UBERON:0002196	80.66	gold quality
pituitary gland	UBERON:0000007	80.38	gold quality
anterior cingulate cortex	UBERON:0009835	80.05	gold quality
hypothalamus	UBERON:0001898	79.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	79.79	gold quality
primary visual cortex	UBERON:0002436	79.63	gold quality
adrenal tissue	UBERON:0018303	79.58	gold quality
epithelium of nasopharynx	UBERON:0001951	79.55	gold quality
kidney	UBERON:0002113	79.55	gold quality
nasopharynx	UBERON:0001728	79.54	gold quality
nucleus accumbens	UBERON:0001882	79.17	gold quality
upper lobe of left lung	UBERON:0008952	78.87	gold quality
ileal mucosa	UBERON:0000331	78.48	gold quality
caudate nucleus	UBERON:0001873	78.31	gold quality
kidney epithelium	UBERON:0004819	78.08	gold quality
cerebellar vermis	UBERON:0004720	78.07	silver quality
upper lobe of lung	UBERON:0008948	77.91	gold quality
amygdala	UBERON:0001876	77.89	gold quality
frontal cortex	UBERON:0001870	77.78	gold quality
neocortex	UBERON:0001950	77.60	gold quality
germinal epithelium of ovary	UBERON:0001304	76.93	gold quality
middle temporal gyrus	UBERON:0002771	76.75	silver quality
forebrain	UBERON:0001890	76.41	gold quality
buccal mucosa cell	CL:0002336	76.38	gold quality
cortex of kidney	UBERON:0001225	76.31	gold quality
cerebral cortex	UBERON:0000956	76.20	gold quality
Brodmann (1909) area 23	UBERON:0013554	75.96	gold quality
occipital lobe	UBERON:0002021	75.36	gold quality
lung	UBERON:0002048	75.20	gold quality
putamen	UBERON:0001874	75.08	gold quality
duodenum	UBERON:0002114	74.81	gold quality
gall bladder	UBERON:0002110	74.13	gold quality
brain	UBERON:0000955	74.09	gold quality
Ammon’s horn	UBERON:0001954	73.88	gold quality
corpus callosum	UBERON:0002336	73.27	gold quality
left lobe of thyroid gland	UBERON:0001120	73.25	gold quality
thyroid gland	UBERON:0002046	73.25	gold quality
deltoid	UBERON:0001476	72.65	silver quality
right lobe of thyroid gland	UBERON:0001119	72.54	gold quality
right adrenal gland cortex	UBERON:0035827	72.54	gold quality
nasal cavity mucosa	UBERON:0001826	72.48	gold quality
substantia nigra	UBERON:0002038	71.91	gold quality
adult organism	UBERON:0007023	71.81	gold quality
temporal lobe	UBERON:0001871	71.47	gold quality
right adrenal gland	UBERON:0001233	71.19	gold quality
left adrenal gland	UBERON:0001234	71.07	gold quality
midbrain	UBERON:0001891	71.01	gold quality
adrenal gland	UBERON:0002369	70.96	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	70.81	gold quality
left ventricle myocardium	UBERON:0006566	70.36	gold quality
left adrenal gland cortex	UBERON:0035825	70.24	gold quality
adrenal cortex	UBERON:0001235	70.16	gold quality
endometrium	UBERON:0001295	70.13	gold quality
spinal cord	UBERON:0002240	70.09	gold quality
cardiac muscle of right atrium	UBERON:0003379	69.88	gold quality
tendon of biceps brachii	UBERON:0008188	67.49	gold quality
body of stomach	UBERON:0001161	67.40	gold quality
endocervix	UBERON:0000458	67.33	gold quality
stomach	UBERON:0000945	67.30	gold quality
left uterine tube	UBERON:0001303	67.29	gold quality
upper arm skin	UBERON:0004263	67.15	gold quality
caput epididymis	UBERON:0004358	67.05	gold quality
trachea	UBERON:0003126	66.35	silver quality
secondary oocyte	CL:0000655	66.32	gold quality
renal medulla	UBERON:0000362	65.97	silver quality
lateral nuclear group of thalamus	UBERON:0002736	65.94	gold quality
fundus of stomach	UBERON:0001160	65.75	gold quality
cardiac atrium	UBERON:0002081	65.21	gold quality
myocardium	UBERON:0002349	65.11	gold quality
right atrium auricular region	UBERON:0006631	64.90	gold quality
superior frontal gyrus	UBERON:0002661	64.85	gold quality
substantia nigra pars compacta	UBERON:0001965	64.76	gold quality
substantia nigra pars reticulata	UBERON:0001966	64.63	gold quality
right lobe of liver	UBERON:0001114	64.62	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	17.79

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Choroid plexus	tissue	43.2
Postcentral gyrus	tissue	29.3
Fallopian tube	tissue	27.8
Testis	tissue	23.7
Hippocampus	tissue	16.8
Nucleus accumbens	tissue	15.9
Locus coeruleus	tissue	12.8
Pancreas	tissue	9.3
Duodenum	tissue	8.1
Periaqueductal gray	tissue	7.8
Lung	tissue	7.3
Kidney	tissue	5.8
Retina	tissue	4.8
Hypothalamus	tissue	4.1
Septum	tissue	3.7
Basal ganglia	tissue	3.6
Pituitary gland	tissue	3.0
Hippocampal formation	tissue	2.8
Pons	tissue	2.3
Thyroid gland	tissue	2.3
Amygdala	tissue	2.2
Ventral forebrain	tissue	2.2
Stomach 1	tissue	2.0
Thalamus	tissue	1.9
Gallbladder	tissue	1.9
Olfactory bulb	tissue	1.8
Parathyroid gland	tissue	1.7
Epididymis	tissue	1.7
Putamen	tissue	1.6
Corpus callosum	tissue	1.6
Adrenal gland	tissue	1.5
Cerebral cortex	tissue	1.4
Medulla oblongata	tissue	1.4
Temporal cortex	tissue	1.4
Midbrain	tissue	1.3
Substantia nigra	tissue	1.2
Retrosplenial and cingulate cortex	tissue	1.2
Insular cortex	tissue	1.2
Prefrontal cortex	tissue	1.1
Retrosplenial cortex	tissue	1.1
Endometrium 1	tissue	1.0
Superior colliculi	tissue	1.0
Cerebellum	tissue	1.0
Small intestine	tissue	1.0
Entorhinal cortex	tissue	1.0
Skin 1	tissue	0.9
Bone marrow	tissue	0.9
Somatosensory cortex	tissue	0.9
Occipital cortex	tissue	0.9
Cervix	tissue	0.8
Caudate putamen	tissue	0.8
Motor cortex	tissue	0.7
Spinal cord	tissue	0.7
Heart muscle	tissue	0.6
Seminal vesicle	tissue	0.5
Placenta	tissue	0.5
Liver	tissue	0.5
Spleen	tissue	0.4
Prostate	tissue	0.4
Lymph node	tissue	0.3

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Periaquaductal grey, lateral (32.5), Nucleus tractus solitarii (29.8), Precentral gyrus (24.7), Postcentral gyrus, middle (24.6), Transversal temporal gyrus, anterior (24.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CFAP221 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

12 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-34C-3P	98.11	65.60	858
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-5196-3P	97.57	65.98	979
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-663B	97.40	62.91	664

Functional genomics

gnomAD constraint: pLI 3.17e-24, LOEUF 1.1, missense Z 0.316 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000413369 — one region, missense o/e 1.01.

Literature-anchored findings (GeneRIF, showing 2)

• plays an important role in ciliary and flagellar biogenesis and motility sperm flagella and the cilia of respiratory epithelial cells and brain ependymal cells in both mice and humans (PMID:18039845)
• These results show that genetic variants in CFAP221 cause Pprimary ciliary dyskinesia (PCD) and that CFAP221 should be considered a candidate gene in cases where PCD is suspected but cilia structure and beat frequency appear normal. (PMID:31636325)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cfap221	ENSDARG00000087107
mus_musculus	Cfap221	ENSMUSG00000036962
rattus_norvegicus	Cfap221	ENSRNOG00000056781

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
Chlamydomonas reinhardtii	A8J6X7	38.3%	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
SCTR-AS1	ncRNA	107105282
PTPN4	protein-coding	5775
SCTR	protein-coding	6344
TMEM177	protein-coding	80775
C2orf76	protein-coding	130355
TMEM37	protein-coding	140738
DBI	protein-coding	1622
STEAP3	protein-coding	55240

Protein

Protein identifiers

Cilia- and flagella-associated protein 221 — Q4G0U5 (reviewed: Q4G0U5)

Alternative names: Primary ciliary dyskinesia protein 1

All UniProt accessions (12): Q4G0U5, H7BZW0, H7C1D6, H7C3Q0, M0QWZ6, M0QZ41, M0QZN4, M0QZV1, M0R095, M0R1M9, M0R1R6, X6RIU2

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in cilium morphogenesis and ciliary function.

Subunit / interactions. Interacts with calmodulin; calcium-dependent.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme.

Tissue specificity. Expressed in ciliated respiratory epithelial cells and brain ependymal cells (at protein level).

Disease relevance. Ciliary dyskinesia, primary, 55 (CILD55) [MIM:279000] An autosomal recessive 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. Male infertility may result from reduced motility of spermatozoa. Some CILD55 affected individuals also exhibit obstructive azoospermia. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the PCDP1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q4G0U5-1	1	yes
Q4G0U5-2	2
Q4G0U5-3	3
Q4G0U5-4	4

RefSeq proteins (1): NP_001257978* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013783	Ig-like_fold	Homologous_superfamily
IPR029676	CFAP221	Family

UniProt features (12 total): splice variant 6, region of interest 2, sequence variant 2, chain 1, sequence conflict 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4G0U5-F1	63.53	0.11

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): connecting piece; flagellar centriole; primary cilium; primary cilium tip

Antibody reliability (HPA): IF supported

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: 150 (showing top): GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_RESPIRATORY_SYSTEM_PROCESS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_ORGANELLE_ASSEMBLY, GOBP_MOTILE_CILIUM_ASSEMBLY, GOBP_CELL_PROJECTION_ORGANIZATION, chr2q14, GOCC_CENTRIOLE, GOCC_CYTOPLASMIC_REGION, GOCC_CILIARY_TIP, GOCC_MOTILE_CILIUM, GOCC_CILIUM, MATZUK_SPERMATOZOA

GO Biological Process (4): cilium movement (GO:0003341), motile cilium assembly (GO:0044458), cilium assembly (GO:0060271), cell projection organization (GO:0030030)

GO Molecular Function (1): calmodulin binding (GO:0005516)

GO Cellular Component (10): manchette (GO:0002177), cytoplasm (GO:0005737), centriole (GO:0005814), cilium (GO:0005929), axoneme (GO:0005930), sperm flagellum (GO:0036126), ciliary tip (GO:0097542), 9+2 motile cilium (GO:0097729), sperm head-tail coupling apparatus (GO:0120212), cytoskeleton (GO:0005856)

GO top-level categories

31 GO namespaces:

Category	Terms
cellular anatomical structure	5
intracellular membraneless organelle	2
microtubule-based movement	1
cilium assembly	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
cellular component organization	1
protein binding	1
microtubule cytoskeleton	1
intracellular anatomical structure	1
microtubule organizing center	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
9+2 motile cilium	1
cilium	1
radial spoke	1
motile cilium	1
inner dynein arm	1
outer dynein arm	1
axonemal central pair	1
axonemal doublet microtubule	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
cilium assembly	BP	mutant phenotype
axoneme	CC	direct assay
centriole	CC	direct assay
ciliary tip	CC	direct assay
cilium	CC	direct assay
sperm head-tail coupling apparatus	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 729 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP221	WDR93	Q6P2C0	716
CFAP221	C1D	Q13901	701
CFAP221	SPEF2	Q9C093	606
CFAP221	SPAG6	O75602	606
CFAP221	CFAP54	Q96N23	579
CFAP221	SPAG17	Q6Q759	570
CFAP221	HYDIN	Q4G0P3	570
CFAP221	CFAP69	A5D8W1	539
CFAP221	SPAG16	Q8N0X2	524
CFAP221	GAS2L2	Q8NHY3	509
CFAP221	RSPH3	Q86UC2	505
CFAP221	CFAP46	Q8IYW2	498
CFAP221	RSPH9	Q9H1X1	498
CFAP221	LRRC56	Q8IYG6	491
CFAP221	DNAAF6	Q9NQM4	490

IntAct

BioGRID (5 interactions; top human partners by supporting records): EEA1 (Cross-Linking-MS (XL-MS)), PARP4 (Proximity Label-MS), PCBP2 (Cross-Linking-MS (XL-MS)), RLIM (Affinity Capture-MS), ZC3HAV1 (Proximity Label-MS)

Disease & clinical

Genetic variants

Variant evidence for CFAP221: 43 ClinVar records (7 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	2
Uncertain significance	4
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (7)

Showing all 7 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
3773992	NM_001271049.2(CFAP221):c.106del (p.Arg36fs)	Pathogenic	criteria provided, single submitter	1
4853905	NM_001271049.2(CFAP221):c.391C>T (p.Arg131Ter)	Pathogenic	criteria provided, single submitter	1
4871845	NM_001271049.2(CFAP221):c.222del (p.Lys74fs)	Likely pathogenic	criteria provided, single submitter	1
4818927	GRCh38/hg38 2q14.2(chr2:119624023-119642209)x1	Likely pathogenic	criteria provided, single submitter	1
3911905	CFAP221, 1-BP DUP, NT1641 (rs779457532)	Pathogenic	no assertion criteria provided	1
3911906	NM_001271049.2(CFAP221):c.1466_1469del (p.Lys489fs)	Pathogenic	no assertion criteria provided	1
3911907	CFAP221, 18,187-BP DEL, EX15-21	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CFAP221’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; 38 predictions of 2,687):

Position(s)	Effect	Δscore	Sites
2:119544639	donor_gain	1.0000
2:119546271–119546272	donor_loss	1.0000	4
2:119559687–119559688	acceptor_loss	1.0000	6
2:119560027–119560028	donor_loss	1.0000	4
2:119604793–119604794	donor_loss	1.0000	5
2:119627650	acceptor_gain	1.0000
2:119627651–119627652	acceptor_loss	1.0000	6
2:119629867	acceptor_gain	1.0000
2:119629956–119629957	donor_loss	1.0000	5
2:119630678–119630679	donor_loss	1.0000	5

AlphaMissense

771 missense substitutions predicted likely pathogenic (of 5,574 scored), across 266 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
D135	8	0.921	0.977
F102	8	0.907	0.978
F125	8	0.899	0.983
F191	8	0.841	0.958
H152	8	0.829	0.944
F204	8	0.808	0.968
F225	7	0.931	0.982
F67	7	0.923	0.981
F360	7	0.876	0.952
W720	7	0.873	0.938
F464	7	0.870	0.956
F193	7	0.869	0.982
N84	7	0.865	0.979
F658	7	0.859	0.959
F244	7	0.855	0.962
F793	7	0.855	0.967
W130	7	0.823	0.961
W378	7	0.788	0.899
F446	7	0.775	0.953
C683	7	0.756	0.901

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	6.89e-05
Lung Adenocarcinoma (TCGA)	favorable	0.000892

Disease associations

OMIM: gene MIM:618704 | disease phenotypes: MIM:279000, MIM:244400

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
primary ciliary dyskinesia	Supportive	Autosomal dominant	2

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
primary ciliary dyskinesia	Definitive	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 (2): Young syndrome (MONDO:0010220), primary ciliary dyskinesia (MONDO:0016575)

Orphanet (2): Primary ciliary dyskinesia (Orphanet:244), Young syndrome (Orphanet:3471)

HPO phenotypes

51 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000027	Azoospermia
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:0002257	Chronic rhinitis
HP:0002566	Intestinal malrotation
HP:0002643	Neonatal respiratory distress
HP:0002837	Recurrent bronchitis
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:0010959	Congenital pulmonary airway malformation
HP:0011109	Chronic sinusitis
HP:0011274	Recurrent mycobacterial infections
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: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:0100582	Nasal polyposis
HP:0100750	Atelectasis

GWAS associations

2 associations:

Study	Trait	p-value
GCST002625_3	Chronic bronchitis and chronic obstructive pulmonary disease	3e-7
GCST008103_77	Bipolar disorder	2e-6

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D002925	Ciliary Motility Disorders	C08.200; C09.150; C16.131.077.245.500; C16.320.184.500
D007619	Kartagener Syndrome	C08.127.384.500; C08.200.531; C08.695.501; C09.150.531; C14.240.400.280.500; C14.280.400.280.500; C16.131.077.245.500.531; C16.131.240.400.280.500; C16.131.740.501; C16.131.810.250.500; C16.320.184.500.531; C16.320.480
C536718	Young Syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, affects methylation	2
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	decreases expression	1
2,3-pentanedione	decreases expression	1
benzo(e)pyrene	decreases methylation	1
ferrous chloride	increases expression	1
aflatoxin B2	decreases methylation	1
Glyphosate	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Diacetyl	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Methapyrilene	decreases methylation	1
Smoke	increases abundance, increases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

showing 60 of 76 trials:

NCT	Phase	Status	Title
NCT02871778	Phase 2	COMPLETED	Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia
NCT07318974	Phase 2	ACTIVE_NOT_RECRUITING	Melatonin Therapy for Improving ICSI Outcomes in Women With Diminished Ovarian Reserve
NCT05737485	Phase 1	COMPLETED	Study Evaluating the Safety and Tolerability of RCT1100 in Healthy and PCD Subjects
NCT06600425	Phase 1	COMPLETED	A Study to Assess the Safety, Tolerability, Ciliary Rescue, and Pharmacodynamics of RCT1100 in Adults With PCD
NCT06633757	Phase 1	COMPLETED	Study of Inhaled RCT1100 in Adults With PCD Caused by Pathogenic Mutations in the DNAI1 Gene to Measure Mucociliary Clearance
NCT04901715	Early Phase 1	COMPLETED	Functional Studies of Novel Genes Mutated in Primary Ciliary Dyskinesia II: Genotype to Phenotype
NCT00005650	Not specified	COMPLETED	Genetic Study of Patients With Primary Ciliary Dyskinesia
NCT00323167	Not specified	COMPLETED	Rare Genetic Disorders of the Breathing Airways
NCT00368446	Not specified	COMPLETED	Genetic Disorders of Mucociliary Clearance in Nontuberculous Mycobacterial Lung Disease
NCT00450918	Not specified	COMPLETED	Evaluating Progression of and Diagnostic Tools for Primary Ciliary Dyskinesia in Children and Adolescents
NCT00608556	Not specified	COMPLETED	Dyskinesia, Heterotaxy and Congenital Heart Disease
NCT00686309	Not specified	UNKNOWN	Comparison of On-line and Off-line Measurements of Exhaled Nitric Oxide (NO)
NCT00722878	Not specified	COMPLETED	Long-term Lung Function and Disease Progression in Children With Early Onset Primary Ciliary Dyskinesia Lung Disease
NCT00739817	Not specified	UNKNOWN	Screening for Primary Ciliary Dyskinesia Using Nasal Nitric Oxide
NCT00783887	Not specified	COMPLETED	Diagnosis of Primary Ciliary Dyskinesia
NCT00807482	Not specified	RECRUITING	Pathogenesis of Primary Ciliary Dyskinesia (PCD) Lung Disease
NCT01070914	Not specified	UNKNOWN	Early Detection and Characterization of Primary Ciliary Dyskinesia
NCT01155115	Not specified	COMPLETED	Inflammatory and Microbiologic Markers in Sputum: Comparing Cystic Fibrosis With Primary Ciliary Dyskinesia
NCT01246258	Not specified	COMPLETED	Otolith Function in Patients With Primary Ciliary Dyskinesia
NCT01929356	Not specified	UNKNOWN	Chest Physiotherapy and Lung Function in Primary Ciliary Dyskinesia
NCT02389049	Not specified	COMPLETED	Genetics of Primary Ciliary Dyskinesia
NCT02419365	Not specified	RECRUITING	International Primary Ciliary Dyskinesia (PCD) Registry
NCT02622061	Not specified	COMPLETED	NIOX VERO Nasal Application in Primary Ciliary Dyskinesia
NCT02699177	Not specified	UNKNOWN	In Vivo Measurements of Nasal Ciliary Beat Frequency by Using Interferometry
NCT02704455	Not specified	NOT_YET_RECRUITING	Registry Study on Primary Ciliary Dyskinesia in Chinese Children
NCT03271840	Not specified	COMPLETED	Registry for Primary Ciliary Dyskinesia
NCT03279965	Not specified	UNKNOWN	MRI in Cystic Fibrosis and Primary Ciliary Dyskinesia
NCT03320382	Not specified	UNKNOWN	Multiple Breath Washout, a Clinimetric Dataset
NCT03370029	Not specified	COMPLETED	Respiratory Muscle Strength, Exercise Capacity and Physical Activity Levels in Children Primary Ciliary Dyskinesia
NCT03494894	Not specified	COMPLETED	Bacteriological Link Between Upper and Lower Airways in Cystic Fibrosis and Primary Ciliary Dyskinesia
NCT03517865	Not specified	ACTIVE_NOT_RECRUITING	International Primary Ciliary Dyskinesia Cohort
NCT03606200	Not specified	RECRUITING	Swiss Primary Ciliary Dyskinesia Registry
NCT03704207	Not specified	RECRUITING	Utility of PCD Diagnostics to Improve Clinical Care
NCT03704896	Not specified	UNKNOWN	PRospective Observational Multicentre Study on VAriability of Lung Function in Stable PCD Patients
NCT03801395	Not specified	COMPLETED	PCD New Gene Discovery
NCT03809091	Not specified	UNKNOWN	WGS of Korean Idiopathic Bronchiectasis
NCT03832491	Not specified	COMPLETED	Effect of Game Based Approach on Oxygenation, Functional Capacity and Quality of Life in Primary Ciliary Dyskinesia
NCT04161313	Not specified	COMPLETED	Respiratory Function, Exercise Capacity and Peripheral Muscle Strength Among Patients With CF, PCD and Healthy Children
NCT04476433	Not specified	COMPLETED	Intervention in Chronic Pediatric Patients and Their Families.
NCT04489472	Not specified	UNKNOWN	The Effect of a Dietary Supplement Rich in Nitric Oxide in Patients Diagnosed With Primary Ciliary Dyskinesia.
NCT04602481	Not specified	RECRUITING	Living With Primary Ciliary Dyskinesia (Living With PCD)
NCT04611516	Not specified	RECRUITING	The Ear-Nose-Throat (ENT) Prospective International Cohort of PCD Patients (EPIC-PCD)
NCT04702243	Not specified	COMPLETED	Defining the Genetic Etiology of Suppurative Lung Disease in Children and Adults
NCT04717115	Not specified	UNKNOWN	Genotype/Phenotype Correlation With Focus on Lung Function in Primary Ciliary Dyskinesia (PCD)
NCT04793724	Not specified	COMPLETED	Respiratory Physiotherapy Performed by Simeox In Patients With Primary Ciliary Dyskinesia
NCT04858191	Not specified	COMPLETED	Utilizing Hyperpolarized 129Xe Magnetic Resonance Imaging in Children With Primary Ciliary Dyskinesia
NCT04895150	Not specified	COMPLETED	Upper Extremity Exercise Capacity, Muscle Oxygenation, Balance in Patients With Primary Ciliary Dyskinesia
NCT04919018	Not specified	COMPLETED	Characterizing the Upper Airway Manifestations in Primary Ciliary Dyskinesia and Primary Immunodeficiencies
NCT04949308	Not specified	UNKNOWN	Nasal Nitric Oxide Across Mutations in Primary Ciliary Dyskinesia
NCT05040607	Not specified	COMPLETED	Physical Fitness, Exercise Capacity and Activities of Daily Living in Primary Ciliary Dyskinesia: a Retrospective Study
NCT05161858	Not specified	COMPLETED	Longitudinal Characterization of Respiratory Tract Exacerbations and Treatment Responses in Primary Ciliary Dyskinesia
NCT05287022	Not specified	RECRUITING	Use of Nasal Nitric Oxide Testing in Improving Primary Ciliary Dyskinesia Clinical Care
NCT05374720	Not specified	TERMINATED	Analysis of the Molecular Composition of Tubal Cilia in Patients With or Without Ectopic Pregnancy
NCT05685186	Not specified	COMPLETED	A Longitudinal, Observational Study of Primary Ciliary Dyskinesia in Adults
NCT05712798	Not specified	COMPLETED	Physiological Responses to Exercise Tests in Primary Ciliary Dyskinesia Compared With Healthy Individuals
NCT05816876	Not specified	COMPLETED	Muscle Function, Exercise Capacity and Physical Activity Level in Primary Ciliary Dyskinesia and Kartagener Syndrome
NCT05889013	Not specified	RECRUITING	Utility of PCD Diagnostics to Improve Clinical Care
NCT05932316	Not specified	UNKNOWN	Evaluating Bronchodilator Response in Patients With Bronchiectasis
NCT05951478	Not specified	RECRUITING	DCP (RaDiCo Cohort) (RaDiCo-DCP)
NCT06028607	Not specified	COMPLETED	Feasibility of Consumption of Nutritional Supplementation in Primary Ciliary Dyskinesia