CCDC134

coiled-coil domain containing 134

Basic information

Region (hg38): 22:41800679-41832164

Links

ENSG00000100147 ∙ NCBI:79879 ∙ OMIM:618788 ∙ HGNC:26185 ∙ Uniprot:Q9H6E4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• osteogenesis imperfecta (Limited), mode of inheritance: AR
• osteogenesis imperfecta, IIA 22 (Limited), mode of inheritance: AR
• osteogenesis imperfecta, IIA 22 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteogenesis imperfecta, type XXII	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	32181939; 34204301; 35019224

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CCDC134 gene.

• Recurrent fractures (1 variants)
• Osteogenesis imperfecta, IIA 22 (1 variants)
• Severe progressive deforming recessive osteogenesis imperfecta (type III) (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCDC134 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		1
missense			17			17
nonsense			1			1
start loss	1					1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding						0
Total	1	0	18	1	0

Highest pathogenic variant AF is 0.00000657

Variants in CCDC134

This is a list of pathogenic ClinVar variants found in the CCDC134 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-41808892-T-C		Recurrent fractures • Osteogenesis imperfecta, IIA 22 • Severe progressive deforming recessive osteogenesis imperfecta (type III)	Pathogenic (Feb 21, 2022)
22-41808990-A-C		not specified	Uncertain significance (Oct 20, 2021)
22-41809924-T-A		not specified	Uncertain significance (Feb 16, 2023)
22-41809953-C-T		not specified	Uncertain significance (Apr 06, 2023)
22-41809971-C-T		not specified	Uncertain significance (Feb 21, 2024)
22-41810275-C-A		not specified	Uncertain significance (May 20, 2024)
22-41810276-G-A		not specified	Uncertain significance (Feb 28, 2023)
22-41813290-G-T		not specified	Uncertain significance (Dec 14, 2022)
22-41813314-C-T		not specified	Uncertain significance (Jan 09, 2024)
22-41813321-C-T		not specified • CCDC134-related condition	Uncertain significance (Nov 17, 2023)
22-41813330-T-C		not specified	Uncertain significance (Nov 12, 2021)
22-41813334-C-T			Likely benign (May 01, 2023)
22-41813357-A-G		not specified	Uncertain significance (May 13, 2022)
22-41813445-G-C			Uncertain significance (Sep 25, 2023)
22-41813767-G-A		not specified	Uncertain significance (Dec 09, 2023)
22-41813811-G-A		not specified	Uncertain significance (Dec 21, 2023)
22-41813814-C-G		not specified	Uncertain significance (Mar 17, 2023)
22-41813818-C-T		not specified	Uncertain significance (Aug 09, 2021)
22-41825725-A-C		not specified	Uncertain significance (Feb 13, 2024)
22-41825753-G-A		not specified	Uncertain significance (Oct 17, 2023)
22-41825791-C-T		not specified	Uncertain significance (Dec 08, 2023)
22-41825809-C-T		Osteogenesis imperfecta, IIA 22	Uncertain significance (Mar 29, 2024)
22-41825813-C-A		not specified	Uncertain significance (Jun 13, 2024)
22-41825816-A-C		not specified	Uncertain significance (Mar 25, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CCDC134	protein_coding	protein_coding	ENST00000255784	6	25621

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.00e-7	0.264	125725	0	23	125748	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0120	136	136	0.997	0.00000813	1517
Missense in Polyphen		63	67.245	0.93687		721
Synonymous	0.644	51	57.2	0.892	0.00000340	444
Loss of Function	0.252	10	10.9	0.918	5.49e-7	120

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.0000544	0.0000544
South Asian	0.000229	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: In extracellular secreted form, promotes proliferation and activation of CD8(+) T cells, suggesting a cytokine-like function (PubMed:25125657). Enhances cytotoxic anti-tumor activity of CD8(+) T cells (PubMed:25125657). May inhibit ERK and JNK signaling activity (PubMed:18087676, PubMed:23070808). May suppress cell migration and invasion activity, via its effects on ERK and JNK signaling (PubMed:23070808). {ECO:0000269|PubMed:18087676, ECO:0000269|PubMed:23070808, ECO:0000269|PubMed:25125657}.

Recessive Scores

• pRec: 0.106

Intolerance Scores

• loftool: 0.373
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.37

Haploinsufficiency Scores

• pHI: 0.0814
• hipred: N
• hipred_score: 0.350
• ghis: 0.660

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.335

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ccdc134
• Phenotype: growth/size/body region phenotype; cellular phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); embryo phenotype; liver/biliary system phenotype; skeleton 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)

Gene ontology

• Cellular component: extracellular region;nucleus;endoplasmic reticulum;membrane
• Molecular function: protein binding