CCDC40

coiled-coil domain containing 40, the group of MicroRNA protein coding host genes|Cilia and flagella associated

Basic information

Region (hg38): 17:80036631-80100613

Links

ENSG00000141519 ∙ NCBI:55036 ∙ OMIM:613799 ∙ HGNC:26090 ∙ Uniprot:Q4G0X9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary ciliary dyskinesia 15 (Definitive), mode of inheritance: AR
• primary ciliary dyskinesia 15 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia 15 (Definitive), mode of inheritance: AR
• primary ciliary dyskinesia 15 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD
• autoimmune disease (Limited), mode of inheritance: AR
• primary ciliary dyskinesia 15 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia 15 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 15	AR	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Pulmonary	Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals have been described with congenital heart anomalies, and awareness may enable early diagnosis and management	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary	20301301; 21131974

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CCDC40 gene.

• Primary ciliary dyskinesia (623 variants)
• not provided (206 variants)
• Primary ciliary dyskinesia 15 (194 variants)
• not specified (92 variants)
• Inborn genetic diseases (47 variants)
• Glycogen storage disease, type II (10 variants)
• CCDC40-related condition (4 variants)
• Kartagener syndrome (2 variants)
• See cases (2 variants)
• Usher syndrome (1 variants)
• Male infertility (1 variants)
• Combined immunodeficiency due to DOCK8 deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCDC40 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	134	14	152
missense	1		292	19	9	321
nonsense	16	4				20
start loss			2			2
frameshift	23	6	1			30
inframe indel			2			2
splice donor/acceptor (+/-2bp)	5	8				13
splice region		1	19	18	2	40
non coding	1	2	23	74	102	202
Total	46	20	324	227	125

Highest pathogenic variant AF is 0.000269

Variants in CCDC40

This is a list of pathogenic ClinVar variants found in the CCDC40 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-80036664-T-G		Primary ciliary dyskinesia	Uncertain significance (Jun 20, 2023)
17-80036665-G-A		Primary ciliary dyskinesia 15	Uncertain significance (Mar 22, 2022)
17-80036673-C-T		Primary ciliary dyskinesia	Uncertain significance (Sep 11, 2019)
17-80036674-G-C		Primary ciliary dyskinesia	Likely benign (Jun 13, 2023)
17-80036675-G-A		Primary ciliary dyskinesia	Uncertain significance (Apr 09, 2023)
17-80036680-C-T		Primary ciliary dyskinesia	Likely benign (Nov 15, 2022)
17-80036681-G-A		Primary ciliary dyskinesia	Uncertain significance (Jun 14, 2023)
17-80036683-G-A		Primary ciliary dyskinesia	Likely benign (Nov 01, 2022)
17-80036685-C-G		Primary ciliary dyskinesia	Uncertain significance (Aug 27, 2021)
17-80036684-G-GCGGGCCGGTAAGC		Primary ciliary dyskinesia	Likely benign (Dec 05, 2023)
17-80036690-C-G		Primary ciliary dyskinesia 15	Uncertain significance (Apr 27, 2017)
17-80036696-G-A		Primary ciliary dyskinesia	Uncertain significance (Jun 26, 2021)
17-80036698-C-G		Primary ciliary dyskinesia	Likely benign (Jan 14, 2022)
17-80036699-G-A		Primary ciliary dyskinesia	Likely benign (Nov 01, 2022)
17-80036702-C-G		Primary ciliary dyskinesia	Benign (Jan 28, 2022)
17-80036703-C-G		Primary ciliary dyskinesia	Likely benign (Oct 02, 2022)
17-80036749-C-A			Benign (Jul 09, 2018)
17-80036911-C-T			Benign (Jul 09, 2018)
17-80037892-A-G			Benign (Jul 09, 2018)
17-80037932-G-T			Benign (Jul 09, 2018)
17-80038043-G-A			Benign (Jul 09, 2018)
17-80038066-G-A			Likely benign (Feb 04, 2019)
17-80038116-A-C		Primary ciliary dyskinesia	Likely benign (Dec 25, 2023)
17-80038125-C-G		Primary ciliary dyskinesia	Uncertain significance (Feb 12, 2024)
17-80038131-C-T		Primary ciliary dyskinesia	Uncertain significance (Aug 28, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CCDC40	protein_coding	protein_coding	ENST00000397545	20	63978

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.82e-17	0.966	124690	1	131	124822	0.000529

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.181	680	667	1.02	0.0000456	7511
Missense in Polyphen		93	99.604	0.9337		1291
Synonymous	0.276	280	286	0.979	0.0000214	2167
Loss of Function	2.49	35	54.9	0.638	0.00000287	629

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00181	0.00177
Ashkenazi Jewish	0.0000994	0.0000993
East Asian	0.000505	0.000501
Finnish	0.000140	0.000139
European (Non-Finnish)	0.000540	0.000538
Middle Eastern	0.000505	0.000501
South Asian	0.000719	0.000686
Other	0.000496	0.000494

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for assembly of dynein regulatory complex (DRC) and inner dynein arm (IDA) complexes, which are responsible for ciliary beat regulation, thereby playing a central role in motility in cilia and flagella (PubMed:21131974). Probably acts together with CCDC39 to form a molecular ruler that determines the 96 nanometer (nm) repeat length and arrangements of components in cilia and flagella (By similarity). Not required for outer dynein arm complexes assembly. Required for axonemal recruitment of CCDC39 (PubMed:21131974). {ECO:0000250|UniProtKB:A8IQT2, ECO:0000269|PubMed:21131974}.
• Disease: DISEASE: Ciliary dyskinesia, primary, 15 (CILD15) [MIM:613808]: 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; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. {ECO:0000269|PubMed:21131974, ECO:0000269|PubMed:22693285, ECO:0000269|PubMed:23255504, ECO:0000269|PubMed:23402890, ECO:0000269|PubMed:25186273}. Note=The disease is caused by mutations affecting the gene represented in this entry. The disease is characterized by primary ciliary dyskinesia with inner dynein arm (IDA) defects and axonemal dizorganisation: defects in CCDC39 and CCDC40 constitute the major cause of this phenotype. {ECO:0000269|PubMed:22693285, ECO:0000269|PubMed:23255504}.

Intolerance Scores

• loftool: 0.844
• rvis_EVS: 1.89
• rvis_percentile_EVS: 97.28

Haploinsufficiency Scores

• pHI: 0.223
• hipred: N
• hipred_score: 0.270
• ghis: 0.498

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.595

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ccdc40
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); embryo phenotype; respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: ccdc40
• Affected structure: pronephric tubule
• Phenotype tag: abnormal
• Phenotype quality: increased diameter

Gene ontology

• Biological process: heart looping;cilium movement;epithelial cilium movement;regulation of cilium beat frequency;flagellated sperm motility;lung development;axoneme assembly;determination of pancreatic left/right asymmetry;inner dynein arm assembly;motile cilium assembly;epithelial cilium movement involved in determination of left/right asymmetry;protein localization to cilium;axonemal dynein complex assembly;determination of digestive tract left/right asymmetry;determination of liver left/right asymmetry
• Cellular component: cytoplasm;cilium;axoneme;motile cilium
• Molecular function: molecular_function