SLC25A38: A Mitochondrial Glycine Transporter Critical for Heme Synthesis
Solute Carrier Family 25 Member 38 – Genetic, Functional, and Clinical Insights
Gene Information Card
| Symbol | SLC25A38 |
|---|---|
| Full Name | Solute Carrier Family 25 Member 38 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p22.1 |
| NCBI Gene ID | 54977 ncbi.nlm.nih.gov/gene/54977 |
| Ensembl ID | ENSG00000144659 |
| UniProt ID | Q96DW6 |
| OMIM ID | 610819 |
| HGNC ID | 26054 |
| Aliases | FLJ20551, MGC138499, MGC138501 |
Description
SLC25A38 encodes a member of the mitochondrial solute carrier family (SLC25). The protein is a mitochondrial inner membrane transporter that imports glycine into the mitochondrial matrix for the first step of heme biosynthesis. Mutations in SLC25A38 cause autosomal recessive congenital sideroblastic anemia (CSA), characterized by microcytic hypochromic anemia and ringed sideroblasts in bone marrow.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Sideroblastic anemia, pyridoxine-refractory, autosomal recessive | Loss of glycine import into mitochondria impairs heme synthesis, leading to iron accumulation in mitochondria | OMIM #616084; ClinVar pathogenic variants |
| Congenital sideroblastic anemia (general) | Defective heme biosynthesis due to reduced mitochondrial glycine availability | PubMed, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Kidney | 6.1 | Low |
| Heart | 4.7 | Low |
| Skeletal muscle | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (erythroleukemia) | 15.2 | High expression; relevant to erythropoiesis |
| HepG2 (hepatocellular carcinoma) | 9.8 | Moderate |
| HEK293 (embryonic kidney) | 5.4 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.676C>T (p.Arg226*) | Nonsense | Rare | Loss of function; truncation |
| c.424G>A (p.Gly142Arg) | Missense | Rare | Impaired glycine transport |
| c.1A>G (p.Met1?) | Start loss | Rare | No protein production |
Mutation functional classification
Loss of Function (LOF)
Most reported SLC25A38 mutations are loss-of-function (nonsense, frameshift, start loss, missense affecting transport), leading to reduced glycine import and heme deficiency.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mechanism described; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • amino acid transmembrane transporter activity (GO:0015171) | • mitochondrial inner membrane (GO:0005743) |
| • heme biosynthetic process (GO:0006783) | • transmembrane transport (GO:0055085) |
Pathways
• Heme biosynthesis (Reactome: R-HSA-189451)
• Mitochondrial glycine import (custom pathway)
Protein Summary
SLC25A38 is a 303-amino-acid mitochondrial inner membrane protein with six transmembrane domains. It functions as a glycine-specific antiporter, exchanging cytosolic glycine for mitochondrial matrix metabolites. The protein is essential for the first step of heme synthesis: condensation of glycine with succinyl-CoA to form 5-aminolevulinic acid (ALA). Deficiency leads to congenital sideroblastic anemia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC25A38 Knockout HEK293 Cell Line | EDJ-KQ15313 | Human | 54977 | Details Get a Quote |
| SLC25A38 Knockout A-549 Cell Line | EDJ-KQ46018 | Human | 54977 | Details Get a Quote |
| SLC25A38 Knockout HeLa Cell Line | EDJ-KQ46020 | Human | 54977 | Details Get a Quote |
| SLC25A38 Knockout HCT 116 Cell Line | EDJ-KQ48210 | Human | 54977 | Details Get a Quote |
| SLC25A38 Knockout ZR-75-1 Cell Line | EDJ-KZ471 | Human | 54977 | Details Get a Quote |
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