SLC25A38

solute carrier family 25 member 38, the group of Solute carrier family 25

Basic information

Region (hg38): 3:39383370-39397351

Links

ENSG00000144659 ∙ NCBI:54977 ∙ OMIM:610819 ∙ HGNC:26054 ∙ Uniprot:Q96DW6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• sideroblastic anemia 2 (Definitive), mode of inheritance: AR
• sideroblastic anemia 2 (Strong), mode of inheritance: AR
• sideroblastic anemia 2 (Definitive), mode of inheritance: AR
• sideroblastic anemia 2 (Strong), mode of inheritance: AR
• autosomal recessive sideroblastic anemia (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Anemia, sideroblastic 2, pyridoxine-refractory	AR	Hematologic	Individuals may have chronic, transfusion-dependent anemia refractory to pyridoxine, and diagnosis may allow early transfusion-based treatment	Hematologic	19412178; 21393332

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC25A38 gene.

• Sideroblastic anemia 2 (41 variants)
• not provided (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC25A38 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	22	1	26
missense	13	2	40	3		58
nonsense	10					10
start loss			2			2
frameshift	13	3				16
inframe indel						0
splice donor/acceptor (+/-2bp)	7	2	1			10
splice region	1		2	2		5
non coding			17	25	24	66
Total	43	7	63	50	25

Highest pathogenic variant AF is 0.0000460

Variants in SLC25A38

This is a list of pathogenic ClinVar variants found in the SLC25A38 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-39383400-G-C		Sideroblastic anemia 2 • X-linked sideroblastic anemia 1	Uncertain significance (Jan 13, 2018)
3-39383422-A-C		X-linked sideroblastic anemia 1 • Sideroblastic anemia 2	Benign/Likely benign (Jun 28, 2018)
3-39383433-G-A		X-linked sideroblastic anemia 1 • Sideroblastic anemia 2	Conflicting classifications of pathogenicity (Jul 07, 2018)
3-39383452-G-A		Sideroblastic anemia 2	Likely benign (Jul 09, 2018)
3-39383488-G-A		Sideroblastic anemia 2 • X-linked sideroblastic anemia 1	Uncertain significance (Jan 12, 2018)
3-39383498-G-A		X-linked sideroblastic anemia 1 • Sideroblastic anemia 2	Uncertain significance (Jan 12, 2018)
3-39383500-G-A		X-linked sideroblastic anemia 1 • Sideroblastic anemia 2	Uncertain significance (Jan 13, 2018)
3-39383506-T-C		X-linked sideroblastic anemia 1 • Sideroblastic anemia 2	Uncertain significance (Jan 13, 2018)
3-39383516-A-G		Refractory anemia with ringed sideroblasts • Sideroblastic anemia 2	Benign/Likely benign (Jun 28, 2018)
3-39383564-G-A		Sideroblastic anemia 2 • Refractory anemia with ringed sideroblasts	Uncertain significance (Jan 12, 2018)
3-39383656-C-T		Sideroblastic anemia 2 • X-linked sideroblastic anemia 1	Uncertain significance (Jan 12, 2018)
3-39383686-G-C		Sideroblastic anemia 2	Uncertain significance (Mar 16, 2018)
3-39383710-C-A		Sideroblastic anemia 2	Uncertain significance (Jan 12, 2018)
3-39383725-A-G			Uncertain significance (Dec 01, 2021)
3-39383726-T-C		SLC25A38-related disorder	Uncertain significance (Jan 01, 2019)
3-39383735-A-G		Sideroblastic anemia 2	Conflicting classifications of pathogenicity (Sep 25, 2024)
3-39383736-C-T		X-linked sideroblastic anemia 1 • Sideroblastic anemia 2	Conflicting classifications of pathogenicity (Jun 01, 2024)
3-39383738-C-G			Pathogenic (May 17, 2023)
3-39383742-T-G			Likely benign (Jan 06, 2024)
3-39383745-G-A			Likely benign (Jul 27, 2022)
3-39383748-G-T			Likely benign (Jun 15, 2022)
3-39383749-C-T			Likely benign (Jun 16, 2023)
3-39383758-C-T		Inborn genetic diseases	Uncertain significance (Jan 04, 2024)
3-39383767-G-A			Uncertain significance (Jul 10, 2023)
3-39383778-G-A			Likely benign (Oct 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC25A38	protein_coding	protein_coding	ENST00000273158	7	14004

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000943	0.794	125671	0	77	125748	0.000306

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.263	162	172	0.943	0.0000104	1951
Missense in Polyphen		63	73.511	0.85701		816
Synonymous	0.537	60	65.5	0.916	0.00000392	646
Loss of Function	1.26	10	15.3	0.653	9.04e-7	166

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000691	0.000691
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000457	0.000457
Middle Eastern	0.000163	0.000163
South Asian	0.000131	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000255|HAMAP-Rule:MF_03064, ECO:0000269|PubMed:19412178, ECO:0000269|PubMed:27476175}.

Recessive Scores

• pRec: 0.117

Intolerance Scores

• loftool: 0.653
• rvis_EVS: 0
• rvis_percentile_EVS: 53.73

Haploinsufficiency Scores

• pHI: 0.214
• hipred: N
• hipred_score: 0.351
• ghis: 0.525

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.847

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Slc25a38
• Phenotype: growth/size/body region phenotype

Gene ontology

• Biological process: heme biosynthetic process;erythrocyte differentiation;glycine import into mitochondrion
• Cellular component: mitochondrion;mitochondrial inner membrane;integral component of membrane
• Molecular function: glycine transmembrane transporter activity