TLCD3B

Chr 16AR

TLC domain containing 3B

Also known as: CORD22, FAM57B, FP1188

The protein is involved in ceramide synthesis and functions as a transmembrane protein that may be targeted by PPAR-gamma. Mutations cause cone-rod dystrophy 22, a retinal degeneration affecting both cone and rod photoreceptors with autosomal recessive inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.516), suggesting intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.521 OMIM phenotype
Clinical SummaryTLCD3B
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.66) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
280 unique Pathogenic / Likely Pathogenic· 35 VUS of 329 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.665
Z-score 2.71
OE 0.16 (0.070.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.18Z-score
OE missense 0.74 (0.630.86)
117 obs / 158.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.16 (0.070.52)
00.351.4
Missense OE0.74 (0.630.86)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 2 / 12.2Missense obs/exp: 117 / 158.9Syn Z: -0.01
DN
0.75top 25%
GOF
0.73top 25%
LOF
0.2483th %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

329 submitted variants in ClinVar

Classification Summary

Pathogenic236
Likely Pathogenic44
VUS35
Likely Benign5
236
Pathogenic
44
Likely Pathogenic
35
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
236
Likely Pathogenic
44
VUS
35
Likely Benign
5
Benign
0
Total320

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TLCD3B · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC