CCDC183

Chr 9

coiled-coil domain containing 183

Also known as: KIAA1984, PARF, bA216L13.7

NCBI Gene: 84960ENSG00000213213UniProt: Q5T5S1OMIM: 615955

The protein encoded by this gene localizes to the ciliary transition zone and is required for proper ciliary function and structure. Mutations cause Bardet-Biedl syndrome, a ciliopathy characterized by retinal degeneration, obesity, polydactyly, renal anomalies, and intellectual disability with autosomal recessive inheritance. The gene shows minimal constraint against loss-of-function variants in population databases.

OMIMResearch
MultiplemechanismLOEUF 0.98
Clinical Summary— CCDC183
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
77 unique Pathogenic / Likely Pathogenic· 107 VUS of 198 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.000
Z-score 1.62
OE 0.66 (0.46–0.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.14Z-score
OE missense 1.02 (0.93–1.12)
321 obs / 314.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.66 (0.46–0.98)
0≤0.351.4
Missense OE1.02 (0.93–1.12)
0≤0.61.4
Synonymous OE1.06
0≤1.21.6
LoF obs/exp: 18 / 27.1Missense obs/exp: 321 / 314.0Syn Z: -0.56
DN
0.77top 25%
GOF
0.6637th %ile
LOF
0.2288th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

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

198 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic71
Likely Pathogenic6
VUS107
Likely Benign10
Benign1
Conflicting2
71
Pathogenic
6
Likely Pathogenic
107
VUS
10
Likely Benign
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
71
0
71
Likely Pathogenic
2
0
4
0
6
VUS
0
100
7
0
107
Likely Benign
1
7
0
2
10
Benign
0
0
1
0
1
Conflicting
—2
Total3107832197

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

View in ClinVar →

Protein Context — Lollipop Plot

CCDC183 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients