TLCD3A

Chr 17

TLC domain containing 3A

Also known as: CT120, FAM57A

NCBI Gene: 79850ENSG00000167695UniProt: Q8TBR7OMIM: 611627

The TLCD3A protein is a membrane-associated protein involved in amino acid transport and glutathione metabolism through interactions with solute carrier proteins and gamma-glutamyltranspeptidase-like enzymes. Mutations in this gene have not been definitively associated with recognized pediatric neurological disorders based on the available information. The gene shows moderate constraint against loss-of-function mutations (LOEUF 0.649), suggesting some intolerance to complete protein loss.

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 0.65
Clinical Summary— TLCD3A
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
61 unique Pathogenic / Likely Pathogenic· 103 VUS of 183 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
0.65LOEUF
pLI 0.256
Z-score 2.40
OE 0.25 (0.11–0.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.22Z-score
OE missense 1.05 (0.92–1.21)
146 obs / 138.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.25 (0.11–0.65)
0≤0.351.4
Missense OE1.05 (0.92–1.21)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 3 / 11.9Missense obs/exp: 146 / 138.7Syn Z: -0.46
DN
0.80top 25%
GOF
0.74top 25%
LOF
0.2190th %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

183 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic55
Likely Pathogenic6
VUS103
Likely Benign8
55
Pathogenic
6
Likely Pathogenic
103
VUS
8
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
55
0
55
Likely Pathogenic
0
0
6
0
6
VUS
1
51
51
0
103
Likely Benign
0
5
3
0
8
Benign
0
0
0
0
0
Total1561150172

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

View in ClinVar →

Protein Context — Lollipop Plot

TLCD3A · 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
A novel mesothelioma molecular classification based on malignant cell differentiation
Liu J et al.·Cancer Cell Int
2025
A machine learning model for periodontitis based on integrative gene expression analysis: validation in an independent patient cohort.
Lee SK et al.·J Periodontal Implant Sci
2026Cohort
Detection of genes positively selected in Cuban Anolis lizards that naturally inhabit hot and open areas and currently thrive in urban areas
Kanamori S et al.·Ecol Evol
2021
Let Time Teach You: A Case Report of a Double Diagnosis of 17P Duplication and Ehlers-Danlos Syndrome
Castronovo P et al.·Genes (Basel)
2022Case report
Integrative epigenomic and transcriptomic profiling reveals organ-specific and coordinated cold stress responses in the brain and gill of Nile tilapia
Li X et al.·Stress Biol
2026
Top 5 full-text resultsSearch PubTator3 ↗
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

No open access results found

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