CCDC115

coiled-coil domain containing 115

Basic information

Region (hg38): 2:130337933-130342699

Links

ENSG00000136710 ∙ NCBI:84317 ∙ OMIM:613734 ∙ HGNC:28178 ∙ Uniprot:Q96NT0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• CCDC115-CDG (Strong), mode of inheritance: AR
• CCDC115-CDG (Strong), mode of inheritance: AR
• CCDC115-CDG (Supportive), mode of inheritance: AR
• CCDC115-CDG (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type IIo	AR	Hematologic	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Craniofacial; Gastrointestinal; Hematologic; Neurologic	26833332
Liver transplant has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CCDC115 gene.

• not provided (2 variants)
• CCDC115-CDG (1 variants)
• Congenital disorders of glycosylation type II (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCDC115 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				8	1	9
missense	1		16	3	1	21
nonsense			2			2
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding				5	3	8
Total	2	0	18	16	5

Highest pathogenic variant AF is 0.0000461

Variants in CCDC115

This is a list of pathogenic ClinVar variants found in the CCDC115 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-130338790-G-A			Benign (Jun 19, 2021)
2-130339124-G-A		CCDC115-related disorder	Likely benign (Jan 08, 2024)
2-130339141-C-A			Likely benign (May 25, 2022)
2-130339144-C-T			Benign (Jan 29, 2024)
2-130339167-G-A		Inborn genetic diseases	Uncertain significance (May 29, 2024)
2-130339179-G-A			Uncertain significance (Mar 13, 2020)
2-130339194-G-A		CCDC115-CDG	Uncertain significance (Dec 07, 2020)
2-130339209-C-T		Inborn genetic diseases	Uncertain significance (Nov 07, 2022)
2-130339212-T-C		Inborn genetic diseases	Uncertain significance (May 16, 2022)
2-130339219-G-A		CCDC115-related disorder	Benign/Likely benign (Dec 21, 2023)
2-130339223-A-G		Inborn genetic diseases	Uncertain significance (Sep 16, 2022)
2-130340897-G-A			Likely benign (Dec 01, 2023)
2-130340932-G-C			Conflicting classifications of pathogenicity (Feb 01, 2024)
2-130340934-C-T		Inborn genetic diseases	Uncertain significance (Feb 21, 2024)
2-130340975-G-A			Likely benign (Nov 06, 2018)
2-130340999-C-T			Likely benign (Oct 27, 2021)
2-130341028-G-A		Inborn genetic diseases	Uncertain significance (Jan 22, 2024)
2-130341033-C-T		CCDC115-CDG	Uncertain significance (May 27, 2022)
2-130341034-G-A			Uncertain significance (Jul 06, 2022)
2-130341650-AG-A			Likely benign (Dec 09, 2023)
2-130341721-TG-T			Pathogenic (Apr 29, 2022)
2-130341758-C-T		CCDC115-related disorder	Benign (Oct 02, 2022)
2-130341809-G-C			Benign (Jun 07, 2020)
2-130341838-C-G			Uncertain significance (Sep 29, 2022)
2-130341842-T-G		Inborn genetic diseases	Uncertain significance (Nov 15, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CCDC115	protein_coding	protein_coding	ENST00000259229	5	4109

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.21e-7	0.111	125696	0	51	125747	0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.109	106	109	0.971	0.00000588	1133
Missense in Polyphen		38	33.56	1.1323		363
Synonymous	-0.261	46	43.8	1.05	0.00000203	385
Loss of Function	-0.332	10	8.93	1.12	3.90e-7	95

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000232	0.000232
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000218	0.000217
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.0000885	0.0000879
Middle Eastern	0.000218	0.000217
South Asian	0.000850	0.000850
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Accessory component of the proton-transporting vacuolar (V)-ATPase protein pump involved in intracellular iron homeostasis. In aerobic conditions, required for intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation. Necessary for endolysosomal acidification and lysosomal degradation (PubMed:28296633). May be involved in Golgi homeostasis (PubMed:26833332). {ECO:0000269|PubMed:26833332, ECO:0000269|PubMed:28296633}.

Recessive Scores

• pRec: 0.0994

Intolerance Scores

• loftool: 0.436
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.42

Haploinsufficiency Scores

• pHI: 0.110
• hipred: N
• hipred_score: 0.144
• ghis: 0.599

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.262

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ccdc115

Gene ontology

• Biological process: cellular iron ion homeostasis;lysosomal lumen acidification;cellular response to increased oxygen levels;vacuolar proton-transporting V-type ATPase complex assembly;lysosomal protein catabolic process
• Cellular component: lysosome;endosome;endoplasmic reticulum;endoplasmic reticulum-Golgi intermediate compartment;membrane;vacuolar proton-transporting V-type ATPase complex;COPI-coated vesicle;extrinsic component of endoplasmic reticulum membrane
• Molecular function: unfolded protein binding