CCDC134

Chr 22AR

coiled-coil domain containing 134

Also known as: OI22

NCBI Gene: 79879ENSG00000100147UniProt: Q9H6E4

Enables protein-macromolecule adaptor activity. Involved in positive regulation of signal transduction; regulation of ossification; and regulation of protein glycosylation. Located in cytosol and intracellular membrane-bounded organelle. Is active in endoplasmic reticulum lumen. Implicated in osteogenesis imperfecta. [provided by Alliance of Genome Resources, Apr 2025]

Primary Disease Associations & Inheritance

Osteogenesis imperfecta, type XXIIMIM #619795
AR
74
ClinVar variants
20
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CCDC134
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 45 VUS of 74 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.54LOEUF
pLI 0.000
Z-score 0.25
OE 0.92 (0.56–1.54)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.01Z-score
OE missense 1.00 (0.87–1.15)
136 obs / 136.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.92 (0.56–1.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.87–1.15)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.89
0≤1.21.6
LoF obs/exp: 10 / 10.9Missense obs/exp: 136 / 136.4Syn Z: 0.64

ClinVar Variant Classifications

74 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic1
VUS45
Likely Benign2
19
Pathogenic
1
Likely Pathogenic
45
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
18
0
19
Likely Pathogenic
0
0
1
0
1
VUS
0
31
13
1
45
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Total03332267

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CCDC134 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Osteogenesis imperfecta, type XXII

MIM #619795

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools