SLC25A38

Summary

SLC25A38 (solute carrier family 25 member 38, HGNC:26054) is a protein-coding gene on chromosome 3p22.1, encoding Mitochondrial glycine transporter (Q96DW6). Mitochondrial glycine transporter that imports glycine into the mitochondrial matrix.

This gene is a member of the mitochondrial carrier family. The encoded protein is required during erythropoiesis and is important for the biosynthesis of heme. Mutations in this gene are the cause of autosomal congenital sideroblastic anemia (anemia, sideroblastic, 2, pyridoxine-refractory). A related pseudogene is found on chromosome 1.

Source: NCBI Gene 54977 — RefSeq curated summary.

At a glance

• Gene–disease (curated): sideroblastic anemia 2 (Definitive, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 249 total — 47 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 8
• MANE Select transcript: NM_017875

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26054
Approved symbol	SLC25A38
Name	solute carrier family 25 member 38
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20551
Ensembl gene	ENSG00000144659
Ensembl biotype	protein_coding
OMIM	610819
Entrez	54977

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 14 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000431510, ENST00000642442, ENST00000642683, ENST00000642978, ENST00000643672, ENST00000645280, ENST00000645630, ENST00000648579, ENST00000650617, ENST00000885741, ENST00000885742, ENST00000885743, ENST00000885744, ENST00000929325, ENST00000949226, ENST00000949227

RefSeq mRNA: 2 — MANE Select: NM_017875 NM_001354798, NM_017875

CCDS: CCDS2685

Canonical transcript exons

ENST00000650617 — 7 exons

Exon	Start	End
ENSE00000966337	39389495	39389616
ENSE00001119519	39391853	39392021
ENSE00001119520	39390423	39390507
ENSE00001119521	39394410	39394576
ENSE00001119522	39396398	39397351
ENSE00003790340	39391441	39391620
ENSE00003835316	39383370	39383793

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 95.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.8173 / max 339.8121, expressed in 1810 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36128	22.1197	1788
36129	7.2713	1739
36131	0.9182	257
36130	0.2421	98
36133	0.1390	12
36132	0.0703	14
36135	0.0412	10
36134	0.0156	7

Top tissues by expression

281 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	95.05	gold quality
right lobe of thyroid gland	UBERON:0001119	95.02	gold quality
left lobe of thyroid gland	UBERON:0001120	94.73	gold quality
right lobe of liver	UBERON:0001114	94.46	gold quality
rectum	UBERON:0001052	94.24	gold quality
right uterine tube	UBERON:0001302	94.06	gold quality
thyroid gland	UBERON:0002046	93.98	gold quality
right adrenal gland cortex	UBERON:0035827	93.94	gold quality
right adrenal gland	UBERON:0001233	93.74	gold quality
mucosa of transverse colon	UBERON:0004991	93.45	gold quality
left adrenal gland	UBERON:0001234	93.26	gold quality
left ovary	UBERON:0002119	93.20	gold quality
body of stomach	UBERON:0001161	93.10	gold quality
left adrenal gland cortex	UBERON:0035825	93.09	gold quality
gastrocnemius	UBERON:0001388	92.96	gold quality
secondary oocyte	CL:0000655	92.90	gold quality
granulocyte	CL:0000094	92.88	gold quality
adrenal cortex	UBERON:0001235	92.72	gold quality
muscle of leg	UBERON:0001383	92.65	gold quality
pancreas	UBERON:0001264	92.53	gold quality
right ovary	UBERON:0002118	92.49	gold quality
adenohypophysis	UBERON:0002196	92.40	gold quality
adrenal gland	UBERON:0002369	92.32	gold quality
transverse colon	UBERON:0001157	92.28	gold quality
right coronary artery	UBERON:0001625	92.09	gold quality
descending thoracic aorta	UBERON:0002345	91.94	gold quality
lymph node	UBERON:0000029	91.86	gold quality
metanephros cortex	UBERON:0010533	91.78	gold quality
ovary	UBERON:0000992	91.77	gold quality
pituitary gland	UBERON:0000007	91.75	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.77

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting SLC25A38, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-6877-3P	98.98	65.83	560
HSA-MIR-6819-3P	98.95	65.57	572
HSA-MIR-5001-3P	98.91	67.28	1394

Literature-anchored findings (GeneRIF, showing 17)

• Twelve CSA probands had biallelic mutations in SLC25A38 (PMID:19731322)
• Mutations in the SLC25A38 gene cause severe, non-syndromic, microcytic/hypochromic sideroblastic anemia in many populations. (PMID:21393332)
• Our study identifies appoptosin as a crucial player in apoptosis and a novel pro-apoptotic protein involved in neuronal cell death. (PMID:23115192)
• Compares and contrasts all the known human SLC25A* genes and includes functional information. (PMID:23266187)
• Several missense mutations are found in SLC25A38 in a Chinese population with congenital sideroblastic anemia. (PMID:24323989)
• Letter/Case Report: novel frameshift mutation in SLC25A38 causing congenital sideroblastic anaemia. (PMID:25512395)
• This study findings reveal a novel role for appoptosin in neurological disorders with tau neuropathology, linking caspase-3-mediated tau cleavage to synaptic dysfunction and behavioral/motor defects. (PMID:26335643)
• Appoptosin can interact with mitochondrial outer-membrane fusion proteins and regulates mitochondrial morphology. (PMID:26813789)
• Given the tolerability of glycine and folate in humans, this study points to a potential novel treatment for SLC25A38 congenital sideroblastic anemia (PMID:26821380)
• the biochemical and molecular characterization of yeast Hem25p and human SLC25A38, providing evidence that they are mitochondrial carriers for glycine. In particular, the hem25Delta mutant manifests a defect in the biosynthesis of delta-aminolevulinic acid and displays reduced levels of downstream heme and mitochondrial cytochromes. (PMID:27476175)
• report confirms the considerable variability in manifestations among patients with ALAS2 or SLC25A38 mutations and draws attention to differences in the assessment and the monitoring of iron overload and its complications (PMID:28772256)
• These findings suggest that sideroblastic anemia must be considered a possible etiology in cases with unexplained hemolytic anemia. Furthermore, mutations in SLC25A38 gene could be a prevalent cause of congenital sideroblastic anemia (CSA) in the Iranian population. (PMID:29499877)
• Dentate gyrus volume deficit in schizophrenia. (PMID:31155012)
• Novel frameshift variant (c.409dupG) in SLC25A38 is a common cause of congenital sideroblastic anaemia in the Indian subcontinent. (PMID:32605921)
• Clinical characterization and hematopoietic stem cell transplant outcomes for congenital sideroblastic anemia caused by a novel pathogenic variant in SLC25A38. (PMID:32790119)
• SLC25A38 congenital sideroblastic anemia: Phenotypes and genotypes of 31 individuals from 24 families, including 11 novel mutations, and a review of the literature. (PMID:34298585)
• SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma. (PMID:35411037)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc25a38a	ENSDARG00000059805
danio_rerio	slc25a38b	ENSDARG00000074533
mus_musculus	Slc25a38	ENSMUSG00000032519
rattus_norvegicus	Slc25a38	ENSRNOG00000018552

Paralogs (49): SLC25A13 (ENSG00000004864), SLC25A5 (ENSG00000005022), SLC25A39 (ENSG00000013306), SLC25A40 (ENSG00000075303), SLC25A3 (ENSG00000075415), SLC25A43 (ENSG00000077713), SLC25A24 (ENSG00000085491), SLC25A1 (ENSG00000100075), SLC25A17 (ENSG00000100372), SLC25A14 (ENSG00000102078), SLC25A15 (ENSG00000102743), SLC25A11 (ENSG00000108528), UCP1 (ENSG00000109424), SLC25A36 (ENSG00000114120), SLC25A12 (ENSG00000115840), SLC25A2 (ENSG00000120329), SLC25A51 (ENSG00000122696), SLC25A16 (ENSG00000122912), SLC25A35 (ENSG00000125434), SLC25A19 (ENSG00000125454), SLC25A23 (ENSG00000125648), SLC25A47 (ENSG00000140107), SLC25A52 (ENSG00000141437), SLC25A26 (ENSG00000144741), SLC25A48 (ENSG00000145832), SLC25A37 (ENSG00000147454), SLC25A25 (ENSG00000148339), SLC25A31 (ENSG00000151475), SLC25A4 (ENSG00000151729), SLC25A27 (ENSG00000153291), SLC25A28 (ENSG00000155287), SLC25A44 (ENSG00000160785), SLC25A45 (ENSG00000162241), SLC25A34 (ENSG00000162461), SLC25A32 (ENSG00000164933), SLC25A6 (ENSG00000169100), SLC25A33 (ENSG00000171612), SLC25A30 (ENSG00000174032), UCP3 (ENSG00000175564), UCP2 (ENSG00000175567)

Protein

Protein identifiers

Mitochondrial glycine transporter — Q96DW6 (reviewed: Q96DW6)

Alternative names: Appoptosin, Mitochondrial glycine transporter GlyC, Solute carrier family 25 member 38

All UniProt accessions (8): Q96DW6, A0A2R8Y427, A0A2R8Y553, A0A2R8Y823, A0A2R8YD83, A0A2R8YE85, A0A3B3IT77, C9JT44

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial glycine transporter that imports glycine into the mitochondrial matrix. Plays an important role in providing glycine for the first enzymatic step in heme biosynthesis, the condensation of glycine with succinyl-CoA to produce 5-aminolevulinate (ALA) in the mitochondrial matrix. Required during erythropoiesis. Plays a role as pro-apoptotic protein that induces caspase-dependent apoptosis.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Preferentially expressed in erythroid cells.

Disease relevance. Anemia, sideroblastic, 2, pyridoxine-refractory (SIDBA2) [MIM:205950] A form of sideroblastic anemia not responsive to pyridoxine. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated in the brains of patients with Alzheimer’s disease.

Similarity. Belongs to the mitochondrial carrier (TC 2.A.29) family. SLC25A38 subfamily.

RefSeq proteins (2): NP_001341727, NP_060345* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018108	MCP_transmembrane	Repeat
IPR023395	MCP_dom_sf	Homologous_superfamily
IPR030847	Hem25/SLC25A38	Family

Pfam: PF00153

Catalyzed reactions (Rhea), 1 shown:

• glycine(in) = glycine(out) (RHEA:70715)

UniProt features (16 total): transmembrane region 6, sequence variant 5, repeat 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DW6-F1	82.91	0.39

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 143 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_ERYTHROCYTE_HOMEOSTASIS, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_TETRAPYRROLE_BIOSYNTHETIC_PROCESS, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_MITOCHONDRIAL_TRANSMEMBRANE_TRANSPORT, GOBP_PORPHYRIN_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_AMINO_ACID_TRANSPORT, GOBP_TETRAPYRROLE_METABOLIC_PROCESS, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_PIGMENT_METABOLIC_PROCESS, GOCC_MITOCHONDRIAL_ENVELOPE

GO Biological Process (3): heme biosynthetic process (GO:0006783), erythrocyte differentiation (GO:0030218), glycine import into mitochondrion (GO:1904983)

GO Molecular Function (1): glycine transmembrane transporter activity (GO:0015187)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycine transport	2
porphyrin-containing compound biosynthetic process	1
heme metabolic process	1
pigment biosynthetic process	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
amino acid transmembrane transport	1
import into the mitochondrion	1
carboxylic acid transmembrane transport	1
neutral L-amino acid transmembrane transporter activity	1
carboxylic acid transmembrane transporter activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

750 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC25A38	GLRX5	Q86SX6	940
SLC25A38	ALAS2	P22557	877
SLC25A38	ABCB7	O75027	776
SLC25A38	PPOX	P50336	679
SLC25A38	ABCB6	Q9NP58	664
SLC25A38	UROS	P10746	664
SLC25A38	FECH	P22830	663
SLC25A38	CPOX	P36551	647
SLC25A38	UROD	P06132	642
SLC25A38	TFRC	P02786	636
SLC25A38	ACO1	P21399	619
SLC25A38	PUS1	Q9Y606	606
SLC25A38	SFXN1	Q9H9B4	600
SLC25A38	IREB2	P48200	579
SLC25A38	SLC19A2	O60779	570
SLC25A38	ALAS1	P13196	570

IntAct

7 interactions, top by confidence:

A	B	Type	Score
SLC25A38	SLC25A4	psi-mi:“MI:0914”(association)	0.350
SLC25A38		psi-mi:“MI:0915”(physical association)	0.000
EMG1	SLC25A38	psi-mi:“MI:0915”(physical association)	0.000
ZSCAN16	SLC25A38	psi-mi:“MI:0915”(physical association)	0.000
SLC25A38	SLC25A38	psi-mi:“MI:0915”(physical association)	0.000
NOL12	SLC25A38	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): SLC25A38 (Affinity Capture-Western), SLC25A38 (Affinity Capture-Western), SLC25A38 (Affinity Capture-Western), MFN1 (Affinity Capture-Western), MFN2 (Affinity Capture-Western), MARCH5 (Affinity Capture-Western), SLC25A38 (Two-hybrid), SLC25A38 (Two-hybrid), AGK (Affinity Capture-MS), GALNT2 (Affinity Capture-MS), GALNT7 (Affinity Capture-MS), GOLM1 (Affinity Capture-MS), IKBIP (Affinity Capture-MS), RAB9A (Affinity Capture-MS), SLC25A1 (Affinity Capture-MS)

ESM2 similar proteins: A1CIF6, A1CWA4, A2Q9F0, A3M019, A4RF23, A4RPU0, A5D9W9, A6RAY2, A6RF73, A6S8E0, A6SL61, A6ZXL1, A7ER02, A7F9Y3, A7TIQ0, B0DK57, B0Y4J4, B2MVX9, B2VSU4, B3LH09, P0CAT2, Q01356, Q03829, Q07534, Q0CT66, Q0UUH1, Q1DRJ3, Q2H608, Q2HFL6, Q2UU67, Q499U1, Q4PDL5, Q4WQC5, Q59KC4, Q5AVW1, Q5B717, Q5EAC0, Q6BH02, Q6C6I3, Q6CNY8

Diamond homologs: A1CIF6, A1CWA4, A2Q9F0, A3M019, A4RPU0, A5D9W9, A6RAY2, A6S8E0, A6ZXL1, A7F9Y3, A7TIQ0, B0DK57, B0Y4J4, B2MVX9, B2VSU4, B3LH09, G3XP90, O77792, P0CAT2, P23500, P38702, Q06143, Q07534, Q08CI8, Q08DK4, Q0CT66, Q0II44, Q0V7M4, Q12251, Q1DRJ3, Q2H608, Q2UU67, Q499U1, Q4PDL5, Q4WQC5, Q59KC4, Q5B717, Q5EAC0, Q5RD81, Q5XH95

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

249 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	47
Likely pathogenic	8
Uncertain significance	94
Likely benign	45
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1118	NM_017875.4(SLC25A38):c.349C>T (p.Arg117Ter)	Pathogenic
1121	NM_017875.4(SLC25A38):c.277-1G>A	Pathogenic
1122	NM_017875.4(SLC25A38):c.790A>T (p.Lys264Ter)	Pathogenic
1172473	NM_017875.4(SLC25A38):c.207_214del (p.Met70fs)	Pathogenic
1172474	NM_017875.4(SLC25A38):c.276+1G>A	Pathogenic
1172475	NM_017875.4(SLC25A38):c.277-2A>C	Pathogenic
1172476	NM_017875.4(SLC25A38):c.362del (p.Pro121fs)	Pathogenic
1172477	NM_017875.4(SLC25A38):c.388G>A (p.Gly130Arg)	Pathogenic
1172478	NM_017875.4(SLC25A38):c.457-1G>T	Pathogenic
1172479	NM_017875.4(SLC25A38):c.475del (p.Glu159fs)	Pathogenic
1172481	NM_017875.4(SLC25A38):c.792+5G>C	Pathogenic
1172482	NM_017875.4(SLC25A38):c.809dup (p.Phe271fs)	Pathogenic
1172483	NM_017875.4(SLC25A38):c.305G>A (p.Gly102Glu)	Pathogenic
1172484	NM_017875.4(SLC25A38):c.913T>C (p.Ter305Arg)	Pathogenic
1172485	NM_017875.4(SLC25A38):c.480dup (p.Ile161fs)	Pathogenic
1172487	NM_017875.4(SLC25A38):c.672delinsTT (p.Ile225fs)	Pathogenic
1172488	NM_017875.4(SLC25A38):c.401G>A (p.Arg134His)	Pathogenic
1172489	NM_017875.4(SLC25A38):c.175C>T (p.Gln59Ter)	Pathogenic
1172491	NM_017875.4(SLC25A38):c.336_346del (p.Lys112fs)	Pathogenic
1172492	NM_017875.4(SLC25A38):c.389G>A (p.Gly130Glu)	Pathogenic
1172494	NM_017875.4(SLC25A38):c.832C>G (p.Arg278Gly)	Pathogenic
1172496	NM_017875.4(SLC25A38):c.281T>A (p.Ile94Asn)	Pathogenic
1172497	NM_017875.4(SLC25A38):c.469G>C (p.Gly157Arg)	Pathogenic
1172498	NM_017875.4(SLC25A38):c.689T>C (p.Leu230Pro)	Pathogenic
1172499	NM_017875.4(SLC25A38):c.260G>A (p.Trp87Ter)	Pathogenic
1172500	NM_017875.4(SLC25A38):c.429_431delinsAG (p.Ile144fs)	Pathogenic
1172501	NM_017875.4(SLC25A38):c.324_330del (p.Leu108_Tyr109insTer)	Pathogenic
1172502	NM_017875.4(SLC25A38):c.858del (p.Ala287fs)	Pathogenic
1172503	NM_017875.4(SLC25A38):c.227_236del (p.Lys76fs)	Pathogenic
1172504	NM_017875.4(SLC25A38):c.276+1G>T	Pathogenic

SpliceAI

1287 predictions. Top by Δscore:

Variant	Effect	Δscore
3:39391974:G:GT	donor_gain	1.0000
3:39391975:A:T	donor_gain	1.0000
3:39394408:A:AG	acceptor_gain	1.0000
3:39394409:G:GA	acceptor_gain	1.0000
3:39394409:GAC:G	acceptor_gain	1.0000
3:39394409:GACCA:G	acceptor_gain	1.0000
3:39394575:AA:A	donor_gain	1.0000
3:39394577:G:GG	donor_gain	1.0000
3:39394590:A:AG	donor_gain	1.0000
3:39394590:A:G	donor_gain	1.0000
3:39383791:ATGGT:A	donor_loss	0.9900
3:39383792:TGGT:T	donor_loss	0.9900
3:39383793:GGTGA:G	donor_loss	0.9900
3:39383794:GTGAG:G	donor_loss	0.9900
3:39383795:T:A	donor_loss	0.9900
3:39389685:T:G	donor_gain	0.9900
3:39390498:G:T	donor_gain	0.9900
3:39390508:G:GG	donor_gain	0.9900
3:39390523:GGTC:G	donor_gain	0.9900
3:39391439:A:AG	acceptor_gain	0.9900
3:39391440:G:GG	acceptor_gain	0.9900
3:39391851:AGAGT:A	acceptor_gain	0.9900
3:39391852:GA:G	acceptor_gain	0.9900
3:39391852:GAGT:G	acceptor_gain	0.9900
3:39391852:GAGTG:G	acceptor_gain	0.9900
3:39392034:G:GT	donor_gain	0.9900
3:39394407:CA:C	acceptor_loss	0.9900
3:39394409:GA:G	acceptor_gain	0.9900
3:39394409:GACC:G	acceptor_gain	0.9900
3:39394573:CAAAG:C	donor_loss	0.9900

AlphaMissense

1958 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:39391608:G:C	K148N	0.999
3:39391608:G:T	K148N	0.999
3:39396473:T:A	W290R	0.999
3:39396473:T:C	W290R	0.999
3:39389534:A:C	S37R	0.998
3:39389536:T:A	S37R	0.998
3:39389536:T:G	S37R	0.998
3:39389581:A:C	K52N	0.998
3:39389581:A:T	K52N	0.998
3:39391967:T:C	F191L	0.998
3:39391969:C:A	F191L	0.998
3:39391969:C:G	F191L	0.998
3:39394509:A:T	K242I	0.998
3:39394510:A:C	K242N	0.998
3:39394510:A:T	K242N	0.998
3:39389526:G:A	G34D	0.997
3:39391983:T:C	L196P	0.997
3:39394464:C:A	A227D	0.997
3:39394476:C:A	A231D	0.997
3:39396446:C:A	R281S	0.997
3:39396465:C:A	A287E	0.997
3:39389543:T:C	C40R	0.996
3:39389580:A:T	K52I	0.996
3:39391457:T:A	V98D	0.996
3:39391468:G:A	G102R	0.996
3:39391468:G:C	G102R	0.996
3:39391469:G:A	G102E	0.996
3:39391477:T:C	F105L	0.996
3:39391479:T:A	F105L	0.996
3:39391479:T:G	F105L	0.996

dbSNP variants (sampled 300 via entrez): RS1000064873 (3:39385596 C>T), RS1000116305 (3:39383057 C>A), RS1000441735 (3:39382521 A>G), RS1000615805 (3:39396084 C>A), RS1000628402 (3:39388496 G>A), RS1000748086 (3:39388807 A>C), RS1001790104 (3:39381742 G>C), RS1002018562 (3:39387476 G>A,T), RS1002178959 (3:39382407 T>C), RS1002232412 (3:39394101 A>C,G), RS1002284642 (3:39394446 T>C), RS1002405364 (3:39388113 C>T), RS1002473625 (3:39383531 C>G,T), RS1003184175 (3:39384749 G>A,T), RS1003573073 (3:39396887 A>G)

Disease associations

OMIM: gene MIM:610819 | disease phenotypes: MIM:205950

GenCC curated gene-disease

Disease	Classification	Inheritance
sideroblastic anemia 2	Definitive	Autosomal recessive
autosomal recessive sideroblastic anemia	Supportive	Autosomal recessive

Mondo (2): sideroblastic anemia 2 (MONDO:0008785), autosomal recessive sideroblastic anemia (MONDO:0016828)

Orphanet (1): Autosomal recessive sideroblastic anemia (Orphanet:260305)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001903	Anemia
HP:0001924	Sideroblastic anemia
HP:0003281	Increased circulating ferritin concentration
HP:0003593	Infantile onset
HP:0012463	Elevated transferrin saturation
HP:0025066	Decreased mean corpuscular volume
HP:0032231	Hypochromia

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567145	Anemia, Sideroblastic, Pyridoxine-Refractory, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC25 mitochondrial vitamin and co-factor carriers subfamily

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
monomethylarsonous acid	increases expression	1
K 7174	increases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Ozone	affects expression, increases abundance	1
Phenobarbital	affects expression	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Thiram	increases expression	1
Tunicamycin	increases expression	1
Valproic Acid	affects expression	1
Cyclosporine	increases expression	1
Thapsigargin	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3H8	Abcam HEK293T SLC25A38 KO	Transformed cell line	Female
CVCL_D4K3	HCT116-SLC25A38-KO-c11	Cancer cell line	Male
CVCL_D4K4	HCT116-SLC25A38-KO-c9	Cancer cell line	Male
CVCL_E1FD	Ubigene ZR-75-1 SLC25A38 KO	Cancer cell line	Female
CVCL_TM40	HAP1 SLC25A38 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.