CCDC174
Chr 3ARcoiled-coil domain containing 174
Also known as: C3orf19, HSPC212, IHPM, IHPMR, ctr1
CCDC174 encodes a nuclear protein that is part of the exon junction complex involved in RNA processing, translation, and nonsense-mediated mRNA decay, and interacts with eukaryotic translation initiation factor 4A isoform 3. Mutations cause autosomal recessive infantile hypotonia with psychomotor retardation, presenting in early infancy with developmental delays and muscle weakness. The gene shows tolerance to loss-of-function variants in the general population (low pLI score), which is consistent with its recessive inheritance pattern.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
156 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 0 | 22 | 0 | 23 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 1 | 76 | 2 | 1 | 80 |
Likely Benign | 0 | 9 | 4 | 12 | 25 |
Benign | 0 | 3 | 14 | 2 | 19 |
| Total | 2 | 88 | 43 | 15 | 148 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CCDC174 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools