CCDC22

coiled-coil domain containing 22, the group of CCC complex

Basic information

Region (hg38): X:49235469-49250520

Previous symbols: [ "CXorf37" ]

Links

ENSG00000101997 ∙ NCBI:28952 ∙ OMIM:300859 ∙ HGNC:28909 ∙ Uniprot:O60826 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Ritscher-Schinzel syndrome 2 (Limited), mode of inheritance: XL
• Ritscher-Schinzel syndrome (Supportive), mode of inheritance: AR
• Ritscher-Schinzel syndrome 2 (Strong), mode of inheritance: XL
• Ritscher-Schinzel syndrome 2 (Moderate), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ritscher-Schinzel syndrome 2	XL	Cardiovascular	Individuals have been described with congenital heart anomalies, and awareness may enable early diagnosis and management	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic	21826058; 24916641

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CCDC22 gene.

• not provided (70 variants)
• Ritscher-Schinzel syndrome 2 (34 variants)
• not specified (25 variants)
• Inborn genetic diseases (21 variants)
• CCDC22-related condition (3 variants)
• Intellectual disability (1 variants)
• Insulin-dependent diabetes mellitus secretory diarrhea syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCDC22 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			1	19	2	22
missense			67	14	3	84
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	3		5
non coding			6		1	7
Total	0	0	75	33	6

Variants in CCDC22

This is a list of pathogenic ClinVar variants found in the CCDC22 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-49235638-T-C		Ritscher-Schinzel syndrome 2 • CCDC22-related disorder	Uncertain significance (Feb 23, 2024)
X-49235685-A-C		Ritscher-Schinzel syndrome 2	Uncertain significance (Jan 01, 2022)
X-49235685-A-G		Ritscher-Schinzel syndrome 2 • Ritscher-Schinzel syndrome 1	Pathogenic (Jan 01, 2012)
X-49237077-C-T		CCDC22-related disorder	Likely benign (Jan 09, 2023)
X-49237116-C-T		not specified	Likely benign (Sep 21, 2017)
X-49237128-T-G			Likely benign (Jul 25, 2018)
X-49237145-C-T		Ritscher-Schinzel syndrome 2	Uncertain significance (Jun 17, 2019)
X-49237159-C-T			Likely benign (Jun 01, 2022)
X-49237162-C-T		not specified	Uncertain significance (Dec 11, 2023)
X-49237169-T-A			Uncertain significance (Oct 01, 2020)
X-49237177-G-A		Ritscher-Schinzel syndrome 2 • not specified	Conflicting classifications of pathogenicity (Jan 01, 2024)
X-49237192-C-T		not specified	Uncertain significance (Sep 17, 2021)
X-49237196-G-C			Uncertain significance (Apr 01, 2014)
X-49237225-C-G		Ritscher-Schinzel syndrome 2	Uncertain significance (Apr 06, 2023)
X-49237232-G-A		Ritscher-Schinzel syndrome 2	Uncertain significance (Nov 01, 2023)
X-49242027-T-C			Likely benign (Dec 31, 2019)
X-49242029-C-T		CCDC22-related disorder	Uncertain significance (Aug 01, 2023)
X-49242071-C-T		Ritscher-Schinzel syndrome 2	Uncertain significance (Mar 01, 2023)
X-49242084-C-G		not specified	Uncertain significance (Nov 12, 2021)
X-49242106-C-T		Ritscher-Schinzel syndrome 2 • not specified	Uncertain significance (Mar 02, 2023)
X-49242107-G-A			Uncertain significance (Sep 01, 2023)
X-49242906-C-T		Ritscher-Schinzel syndrome 2	Uncertain significance (Sep 29, 2021)
X-49242907-G-A		Ritscher-Schinzel syndrome 2	Uncertain significance (Mar 07, 2022)
X-49242913-T-C			Benign (Dec 31, 2019)
X-49242923-A-G			Likely benign (May 24, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CCDC22	protein_coding	protein_coding	ENST00000376227	17	15061

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000209	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.29	211	271	0.779	0.0000244	3966
Missense in Polyphen		49	98.817	0.49587		1523
Synonymous	-0.0883	109	108	1.01	0.00000880	1337
Loss of Function	4.56	0	24.2	0.00	0.00000182	386

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in regulation of NF-kappa-B signaling. Promotes ubiquitination of I-kappa-B-kinase subunit IKBKB and its subsequent proteasomal degradation leading to NF-kappa-B activation; the function may involve association with COMMD8 and a CUL1-dependent E3 ubiquitin ligase complex. May down-regulate NF- kappa-B activity via association with COMMD1 and involving a CUL2- dependent E3 ubiquitin ligase complex. Regulates the cellular localization of COMM domain-containing proteins, such as COMMD1 and COMMD10 (PubMed:23563313). Plays a role in copper ion homeostasis. Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association within the CCC complex and cooperation with the WASH complex on early endosomes (PubMed:25355947). {ECO:0000269|PubMed:23563313, ECO:0000269|PubMed:25355947}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Neddylation (Consensus)

Recessive Scores

• pRec: 0.150

Intolerance Scores

• rvis_EVS: 0.71
• rvis_percentile_EVS: 85.68

Haploinsufficiency Scores

• pHI: 0.0912
• hipred: N
• hipred_score: 0.469
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.307

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ccdc22

Gene ontology

• Biological process: cellular copper ion homeostasis;Golgi to plasma membrane transport;cytoplasmic sequestering of NF-kappaB;protein transport;positive regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of I-kappaB kinase/NF-kappaB signaling;post-translational protein modification;positive regulation of ubiquitin-dependent protein catabolic process
• Cellular component: cellular_component;nucleoplasm;endosome;cytosol
• Molecular function: protein binding;cullin family protein binding