CC2D1B

Chr 1AR

coiled-coil and C2 domain containing 1B

Also known as: Lgd1

NCBI Gene: 200014 ENSG00000154222 UniProt: Q5T0F9 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.921 OMIM phenotype

Clinical Summary— CC2D1B

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

166 VUS of 208 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 OE?0.69 (0.53–0.92)

0≤0.351.4

Missense OE?1.13 (1.05–1.21)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 36 / 51.8Missense obs/exp: 570 / 506.1Syn Z: 0.56

This gene — mechanism propensity

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

208 submitted variants in ClinVar

ClinVar

Classification Summary

VUS166

Likely Benign11

Benign3

166

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	166	0	166
Likely Benign	10	1	11
Benign	0	3	3
Total	176	4	180

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

View in ClinVar →

7 pathogenic / likely-pathogenic (of 10) ClinVar copy-number / structural variants overlap CC2D1B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →