CCDC134

protein-coding

coiled-coil domain containing 134

Gene summary

Enables protein-macromolecule adaptor activity. Involved in positive regulation of signal transduction; regulation of glycoprotein biosynthetic process; and regulation of ossification. Located in cytosol. Is active in endoplasmic reticulum lumen. Implicated in osteogenesis imperfecta. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_024821.5

Inheritance

ClinVar variants

P:1U:36B:3

Top phenotype

Osteogenesis imperfecta, type XXII

gnomAD constraint

pLI —, LoF o/e 0.92

Max pathogenic AF

—

Genomic locus

chr22:41,800,679-41,832,164

External References & Databases

Ensembl (ENSG00000100147)

Transcript & Mutation Effects

hg38 • Region Span ~31.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

osteogenesis imperfecta, type XXIILIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030714

Submitter: Labcorp Genetics (formerly Invitae)

osteogenesis imperfecta, type XXIILIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030714

Submitter: Ambry Genetics

osteogenesis imperfectaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019019

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Osteogenesis imperfecta, type XXIIAR

Manifestation: Musculoskeletal

Intervention: General

Rationale: 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

Refs: 32181939; 34204301; 35019224

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CCDC134 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 34

Osteogenesis imperfecta, type XXIITotal: 4

not providedTotal: 3

CCDC134-related conditionTotal: 1

Recurrent fracturesTotal: 1

Severe progressive deforming recessive osteogenesis imperfecta (type III)Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024821.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	2 clinvar		3
missense			32 clinvar	1 clinvar		33
nonsense			1 clinvar			1
start loss	1 clinvar					1
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	0	36	3	0	40

Highest pathogenic variant AF is 0.0000030982735

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024821.5	RefSeq	NP_079097.1	6	MANE Select
ENST00000255784.6	Ensembl	ENSP00000255784.5	6	MANE Select
NM_001304797.2	RefSeq	NP_001291726.1	3	Standard
NM_001382346.1	RefSeq	NP_001369275.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

protein binding

Cellular Component

extracellular region
nucleus
endoplasmic reticulum
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000255784
Coding exons: 6
Length: 25621
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125748
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0120	136	136	0.997	0.00000813	1517
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00023	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.335

Gene Damage Prediction

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