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GeneE
3 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TLDC2
TBC/LysM-associated domain containing 2
Chromosome 20 Β· 20q11.23
NCBI Gene: 140711Ensembl: ENSG00000101342.11HGNC: HGNC:16112UniProt: A0PJX2
6PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
response to oxidative stressnucleusAicardi-Goutieres syndrome 5chilblain lupus 2Aicardi-Goutieres syndromegenetic disorder
✦AI Summary

TLDC2 is a TLDc domain-containing protein that functions as a negative regulator of vacuolar-type ATPase (V-ATPase). Its primary role is to inhibit V-ATPase activity by inducing disassembly of the V-ATPase complex 1. TLDC2 belongs to an evolutionarily conserved family of V-ATPase regulatory proteins, with the TLDc domain being essential for this interaction 2. Beyond V-ATPase regulation, TLDC2 is implicated in protecting neuronal cells against oxidative stress and is required for kidney bicarbonate secretion 1. The protein localizes to the nucleus and responds to oxidative stress conditions. Functionally, TLDC2 represents a distinct class of V-ATPase-interacting regulatory proteins that fine-tune proton pump function through controlled enzyme disassembly rather than simple inhibition. Additionally, TLDC2 has been identified as a hub gene in co-expression networks associated with cutaneous leishmaniasis immune response, suggesting potential roles in host-pathogen interactions and immune signaling 3. The clinical significance of TLDC2 dysfunction may relate to neurological disease phenotypes that mirror V-ATPase deficiency, though direct human disease associations require further investigation.

Sources cited
1
TLDC2 inhibits V-ATPase by inducing disassembly of the V-ATPase complex; provides oxidative stress protection
PMID: 38593795
2
TLDC2 interacts with V-ATPase through its TLDc domain; defines a new class of V-ATPase regulatory proteins
PMID: 34811399
3
TLDC2 identified as hub gene in co-expression networks in cutaneous leishmaniasis lesions
PMID: 39639867
⚠Limited data available β€” This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜20
Aicardi-Goutieres syndrome 5Open Targets
0.19Weak
chilblain lupus 2Open Targets
0.18Weak
Aicardi-Goutieres syndromeOpen Targets
0.17Weak
genetic disorderOpen Targets
0.12Weak
hypoparathyroidism, familial isolated, 2Open Targets
0.06Suggestive
intestinal hypomagnesemia 1Open Targets
0.05Suggestive
Primary hypomagnesemia with secondary hypocalcemiaOpen Targets
0.05Suggestive
pseudohypoparathyroidism type 2Open Targets
0.05Suggestive
22q11.2 deletion syndromeOpen Targets
0.04Suggestive
Familial isolated hypoparathyroidismOpen Targets
0.04Suggestive
Barrett's esophagusOpen Targets
0.04Suggestive
familial isolated hyperparathyroidismOpen Targets
0.04Suggestive
hyperparathyroidismOpen Targets
0.04Suggestive
familial isolated hypoparathyroidism due to agenesis of parathyroid glandOpen Targets
0.04Suggestive
crystal arthropathyOpen Targets
0.04Suggestive
adamantinomaOpen Targets
0.03Suggestive
blue diaper syndromeOpen Targets
0.03Suggestive
skin neoplasmOpen Targets
0.03Suggestive
ulna metaphyseal dysplasia syndromeOpen Targets
0.03Suggestive
skin cancerOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar β†—
Related Genes
OXR1Shared pathway100%NCOA7Shared pathway100%SELENOPShared pathway50%MSRB3Shared pathway50%SCARA3Shared pathway33%CYB5BShared pathway33%
Tissue Expression6 tissues
Lung
100%
Ovary
42%
Liver
22%
Brain
7%
Bone Marrow
5%
Heart
0%
Gene Interaction Network
Click a node to explore
TLDC2OXR1NCOA7SELENOPMSRB3SCARA3CYB5B
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt A0PJX2
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.10LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.78 [0.56–1.10]
RankingsWhere TLDC2 stands among ~20K protein-coding genes
  • #18,231of 20,598
    Most Researched6
  • #11,287of 17,882
    Most Constrained (LOEUF)1.10
Genes detectedTLDC2
Sources retrieved3 papers
Response timeβ€”
πŸ“„ Sources
3
1
Human V-ATPase function is positively and negatively regulated by TLDc proteins.
PMID: 38593795
Structure Β· 2024
1.00
2
The evolutionary conserved TLDc domain defines a new class of (H
PMID: 34811399
Sci Rep Β· 2021
0.67
3
Integrated analysis of lncRNA and mRNA expression profiles in cutaneous leishmaniasis lesions caused by
PMID: 39639867
Front Cell Infect Microbiol Β· 2024
0.33