CC2D1B

Chr 1AR

coiled-coil and C2 domain containing 1B

Also known as: Lgd1

NCBI Gene: 200014ENSG00000154222UniProt: Q5T0F9OMIM: 610055

CC2D1B encodes a transcription factor that binds to specific DNA regulatory elements and represses transcription of neuronal genes, including the serotonin receptor HTR1A. Mutations cause autosomal recessive intellectual developmental disorder. The gene shows no constraint against loss-of-function variants in the general population (pLI near zero), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.921 OMIM phenotype
Clinical Summary— CC2D1B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 168 VUS of 217 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
0.92LOEUF
pLI 0.000
Z-score 2.04
OE 0.69 (0.53–0.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-1.01Z-score
OE missense 1.13 (1.05–1.21)
570 obs / 506.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.69 (0.53–0.92)
0≤0.351.4
Missense OE1.13 (1.05–1.21)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 36 / 51.8Missense obs/exp: 570 / 506.1Syn Z: 0.56
DN
0.6454th %ile
GOF
0.5366th %ile
LOF
0.3260th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

217 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic2
VUS168
Likely Benign11
Benign3
5
Pathogenic
2
Likely Pathogenic
168
VUS
11
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
2
0
2
VUS
0
166
2
0
168
Likely Benign
0
10
0
1
11
Benign
0
0
0
3
3
Total017694189

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

View in ClinVar →

Protein Context — Lollipop Plot

CC2D1B · 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 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 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