SLC25A38

Chr 3AR

solute carrier family 25 member 38

Also known as: SIDBA2

This mitochondrial glycine transporter imports glycine into the mitochondrial matrix to provide substrate for the first step of heme biosynthesis during erythropoiesis. Biallelic mutations cause autosomal recessive congenital sideroblastic anemia that is pyridoxine-refractory, typically presenting in infancy with severe microcytic anemia and iron overload. The gene shows low constraint against loss-of-function variants in population databases.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.111 OMIM phenotype
Clinical SummarySLC25A38
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
69 unique Pathogenic / Likely Pathogenic· 100 VUS of 283 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — SLC25A38
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.11LOEUF
pLI 0.000
Z-score 1.26
OE 0.65 (0.401.11)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.26Z-score
OE missense 0.94 (0.831.07)
162 obs / 171.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.65 (0.401.11)
00.351.4
Missense OE0.94 (0.831.07)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 10 / 15.3Missense obs/exp: 162 / 171.7Syn Z: 0.54
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSLC25A38-related anemia, sideroblastic, pyridoxine-refractoryLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.81top 10%
GOF
0.7127th %ile
LOF
0.2777th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

283 submitted variants in ClinVar

Classification Summary

Pathogenic57
Likely Pathogenic12
VUS100
Likely Benign64
Benign25
Conflicting17
57
Pathogenic
12
Likely Pathogenic
100
VUS
64
Likely Benign
25
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
35
13
9
0
57
Likely Pathogenic
8
3
1
0
12
VUS
1
75
21
3
100
Likely Benign
1
6
32
25
64
Benign
0
0
24
1
25
Conflicting
17
Total45978729275

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SLC25A38 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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