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Last update 08 May 2025

SLC39A12

Last update 08 May 2025

Basic Info

Synonyms

FLJ30499, LIV-1 subfamily of ZIP zinc transporter 8, LZT-Hs8

+ [8]

Introduction

Uniporter that promotes Zn(2+) import from the extracellular space to the cytoplasm across the cell membrane. The transport activity is temperature dependent. May play a role in neurulation and neurite extension. May play a key role in maintaining intracellular zinc content at levels that reduce the inhibitory effects of rises in oxidative stress on spermatogonia and spermatozoa viability during spermatogenesis.

Drugs associated with SLC39A12

APL-9796

Target

SLC39A12

Mechanism

SLC39A12 blockers

Active Org.

Apollo Therapeutics

Originator Org.

Apollo Therapeutics

Active Indication

Pulmonary Arterial Hypertension

Inactive Indication-

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with SLC39A12

NCT06846554

/ RecruitingPhase 2

A Phase 2, Multicentre, Open-Label Trial to Evaluate APL-9796 in Adult Participants With Pulmonary Hypertension (ViTAL-PH)

The AP13CP02 study is a phase 2, open-label, dose escalation trial to determine how safe and tolerable multiple subcutaneous (SC) injections of APL-9796 are for patients with PH. The study will also assess how effective APL-9796 could be for treating patients with PH and whether the body produces antibodies working against APL-9796.
The trial will be conducted in two parts:
* Part A: Up to 36 adults with WHO Group 1 Pulmonary arterial hypertension (PAH).
* Part B (optional): Up to 12 adults with WHO Group 3 - PH associated with ILD (PH-ILD).

Start Date09 Apr 2025

Sponsor / Collaborator

Apollo Therapeutics

ACTRN12624000086561

/ Active, not recruitingPhase 1

A Randomised, Double-blind, Placebo-controlled, Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of Subcutaneous, Ascending Single Doses of AP13 in Healthy Adults

Start Date27 Feb 2024

Sponsor / Collaborator

Avance Clinical Pty Ltd.

100 Clinical Results associated with SLC39A12

100 Translational Medicine associated with SLC39A12

0 Patents (Medical) associated with SLC39A12

Literatures (Medical) associated with SLC39A12

26 Mar 2025·The Journal of Neuroscience

The Astrocytic Zinc Transporter ZIP12 Is a Synaptic Protein That Contributes to Synaptic Zinc Levels in the Mouse Auditory Cortex

Article

Author: Webb, Bradley A ; Manning, Abbey ; Ruby, Rayli ; Mendelson, Benjamin Z ; Dariano, Donald F ; Geldenhuys, Werner J ; Bainer, Kaitlin ; Anderson, Charles T ; Shifflett, Victoria R ; Bender, Philip T R

Synaptically released zinc is a neuronal signaling system that arises from the actions of the presynaptic vesicular zinc transporter protein zinc transporter 3 (ZnT3). Mechanisms that regulate the actions of zinc at synapses are of great importance for many aspects of synaptic signaling in the brain. Here, we identify the astrocytic zinc transporter protein ZIP12 as a candidate mechanism that contributes to zinc clearance at cortical synapses. We identify small-molecule compounds that antagonize the function of ZIP12 in heterologous expression systems, and we use one of these compounds, ZIP12 modulator 8, to increase the concentration of ZnT3-dependent zinc at synapses in the brain of male and female mice to inhibit the activity of neuronal AMPA and NMDA glutamate receptors. These results identify a cellular mechanism and provide a pharmacological toolbox to target the molecular machinery that supports the actions of synaptic zinc in the brain.

01 Feb 2025·Science Bulletin

Plasma membrane-associated calcium signaling modulates zinc homeostasis in Arabidopsis

Article

Author: Zhao, Yusheng ; Chen, Xuanyi ; Javed, Laiba ; Fang, Yanjun ; Ju, Chuanfeng ; Deng, Yuan ; Sun, Lv ; Gao, Yaqi ; Cao, Chenyu ; Wang, Cun

Zinc (Zn) is a crucial micronutrient for all organisms, and its deficiency can significantly hamper crop yield and quality. However, the understanding of the regulatory mechanisms involved in plant Zn signal perception and transduction remains limited. In this study, we discovered that the Ca²⁺-CBL1/4/5/8/9-CIPK3/9/23/26-ZIP12 signaling module effectively responds to Zn deficiency and regulates Zn homeostasis in Arabidopsis thaliana. Furthermore, we determined that CIPK3/9/23/26 interact with the Zn transporter ZIP12 and phosphorylate it primarily at Ser185. This phosphorylation event was crucial for the stability of the ZIP12 protein, suggesting that it regulates the function of ZIP12 in Zn transport. Collectively, our findings identify a plasma membrane-associated calcium signaling pathway that regulates Zn homeostasis in Arabidopsis thaliana. This pathway represents a promising target for molecular breeding approaches aimed at developing crops with enhanced tolerance to Zn deficiency.

01 Jan 2025·Biological Trace Element Research

Effects of Zinc Combined with Metformin on Zinc Homeostasis, Blood-Epididymal Barrier, and Epididymal Absorption in Male Diabetic Mice

Article

Author: Tie, Yanqing ; Li, Huanhuan ; Zhao, Bangrong ; Ma, Jing ; Wang, Shusong ; Zhang, Menghui ; Yang, Yang ; Yang, Chaoju

Diabetes increases the likelihood of germ cell damage, hypogonadism, and male infertility. Diabetes leads to lower zinc (Zn) levels, an important micronutrient for maintaining male fertility, and zinc deficiency can lead to decreased male fertility through multiple mechanisms. The aim of this study was to investigate the effect of combined metformin and zinc administration on epididymis in diabetic mice; 10 of 50 male mice were randomly selected as the control group (group C), and the remaining 40 mice were randomly divided into untreated diabetes group (group D), diabetes + zinc group (group Z), diabetes + metformin group (group M), and diabetes + metformin + zinc group (group ZM) with 10 mice each. Diabetic mice in group Z received oral zinc (10 mg/kg) once daily for 4 weeks; diabetic mice in group M received oral metformin (200 mg/kg) once daily for 4 weeks; diabetic mice in group ZM received oral metformin and zinc once daily for 4 weeks; and groups C and D received the same amount of sterile water by gavage. Overnight fasted mice were sacrificed, and blood samples, mouse epididymides, and sperm were collected for further experiments. In group D, fasting blood glucose and insulin resistance index increased significantly, semen quality, serum insulin, and testosterone decreased, and epididymal structure was disordered. In group D, epididymal tissue zinc, free zinc ions in the caput, and cauda of epididymis and zinc transporter (ZnT2) decreased significantly, while ZIP12, metallothionein (MT), and metal transcription factor (MTF1) increased significantly. In addition, the expressions of blood-epididymal barrier (BEB)-related molecules (including ZO-1 β-catenin and N-cadherin) and aquaporins (AQPs, including AQP3, AQP9, and AQP11) in the epididymis of mice in group D were significantly decreased. In addition, compared with groups D, Z, and M, in the ZM group, the expression of BEB-related molecules (including ZO-1, β-catenin, and N-cadherin) and aquaporins (AQP3, AQP9, and AQP11) in epididymis tissue were significantly increased, and sperm motility and serum testosterone were significantly increased. It was concluded that male diabetic mice have a disturbed epididymal structure and decreased semen quality by causing an imbalance in epididymal zinc homeostasis, BEB, and impaired absorptive function. The combination of zinc and metformin is an effective and safe alternative treatment and provides additional benefits over metformin alone.

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SLC39A12

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