Sideroblastic anemia 2

Summary

Sideroblastic anemia 2 (MONDO:0008785) is a disease caused by SLC25A38 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: SLC25A38 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 111

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	sideroblastic anemia 2
Mondo ID	MONDO:0008785
MeSH	C567145
OMIM	205950
DOID	DOID:0060065
UMLS	C4225425
MedGen	899109
GARD	0018381
Is cancer (heuristic)	no

Also known as: pyridoxine refractory sideroblastic anaemia · pyridoxine refractory sideroblastic anemia · SIDBA2 · sideroblastic anaemia pyridoxine-refractory autosomal recessive · sideroblastic anemia pyridoxine-refractory autosomal recessive

Data availability: 111 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive sideroblastic anemia › sideroblastic anemia 2

Related subtypes (1): sideroblastic anemia 3

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

111 retrieved; paginated sample, class counts are floors:

42 pathogenic, 28 uncertain significance, 16 conflicting classifications of pathogenicity, 6 benign, 6 likely pathogenic, 5 benign/likely benign, 5 likely benign, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1118	NM_017875.4(SLC25A38):c.349C>T (p.Arg117Ter)	SLC25A38	Pathogenic	criteria provided, multiple submitters, no conflicts
1119	NM_017875.4(SLC25A38):c.324_325del (p.Tyr109fs)	SLC25A38	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1121	NM_017875.4(SLC25A38):c.277-1G>A	SLC25A38	Pathogenic	criteria provided, single submitter
1122	NM_017875.4(SLC25A38):c.790A>T (p.Lys264Ter)	SLC25A38	Pathogenic	criteria provided, single submitter
1172473	NM_017875.4(SLC25A38):c.207_214del (p.Met70fs)	SLC25A38	Pathogenic	criteria provided, single submitter
1172474	NM_017875.4(SLC25A38):c.276+1G>A	SLC25A38	Pathogenic	criteria provided, single submitter
1172475	NM_017875.4(SLC25A38):c.277-2A>C	SLC25A38	Pathogenic	criteria provided, single submitter
1172476	NM_017875.4(SLC25A38):c.362del (p.Pro121fs)	SLC25A38	Pathogenic	criteria provided, single submitter
1172477	NM_017875.4(SLC25A38):c.388G>A (p.Gly130Arg)	SLC25A38	Pathogenic	criteria provided, single submitter
1172478	NM_017875.4(SLC25A38):c.457-1G>T	SLC25A38	Pathogenic	criteria provided, single submitter
1172479	NM_017875.4(SLC25A38):c.475del (p.Glu159fs)	SLC25A38	Pathogenic	criteria provided, single submitter
1172481	NM_017875.4(SLC25A38):c.792+5G>C	SLC25A38	Pathogenic	criteria provided, single submitter
1172482	NM_017875.4(SLC25A38):c.809dup (p.Phe271fs)	SLC25A38	Pathogenic	criteria provided, single submitter
1172483	NM_017875.4(SLC25A38):c.305G>A (p.Gly102Glu)	SLC25A38	Pathogenic	criteria provided, single submitter
1172484	NM_017875.4(SLC25A38):c.913T>C (p.Ter305Arg)	SLC25A38	Pathogenic	criteria provided, single submitter
1172485	NM_017875.4(SLC25A38):c.480dup (p.Ile161fs)	SLC25A38	Pathogenic	criteria provided, single submitter
1172487	NM_017875.4(SLC25A38):c.672delinsTT (p.Ile225fs)	SLC25A38	Pathogenic	criteria provided, single submitter
1172488	NM_017875.4(SLC25A38):c.401G>A (p.Arg134His)	SLC25A38	Pathogenic	criteria provided, single submitter
1172489	NM_017875.4(SLC25A38):c.175C>T (p.Gln59Ter)	SLC25A38	Pathogenic	criteria provided, single submitter
1172490	NM_017875.4(SLC25A38):c.832C>T (p.Arg278Ter)	SLC25A38	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1172491	NM_017875.4(SLC25A38):c.336_346del (p.Lys112fs)	SLC25A38	Pathogenic	criteria provided, multiple submitters, no conflicts
1172492	NM_017875.4(SLC25A38):c.389G>A (p.Gly130Glu)	SLC25A38	Pathogenic	criteria provided, single submitter
1172494	NM_017875.4(SLC25A38):c.832C>G (p.Arg278Gly)	SLC25A38	Pathogenic	criteria provided, single submitter
1172496	NM_017875.4(SLC25A38):c.281T>A (p.Ile94Asn)	SLC25A38	Pathogenic	criteria provided, single submitter
1172497	NM_017875.4(SLC25A38):c.469G>C (p.Gly157Arg)	SLC25A38	Pathogenic	criteria provided, single submitter
1172498	NM_017875.4(SLC25A38):c.689T>C (p.Leu230Pro)	SLC25A38	Pathogenic	criteria provided, single submitter
1172499	NM_017875.4(SLC25A38):c.260G>A (p.Trp87Ter)	SLC25A38	Pathogenic	criteria provided, single submitter
1172500	NM_017875.4(SLC25A38):c.429_431delinsAG (p.Ile144fs)	SLC25A38	Pathogenic	criteria provided, single submitter
1172501	NM_017875.4(SLC25A38):c.324_330del (p.Leu108_Tyr109insTer)	SLC25A38	Pathogenic	criteria provided, single submitter
1172502	NM_017875.4(SLC25A38):c.858del (p.Ala287fs)	SLC25A38	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SLC25A38	Definitive	Autosomal recessive	sideroblastic anemia 2	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC25A38	Orphanet:260305	Autosomal recessive sideroblastic anemia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC25A38	HGNC:26054	ENSG00000144659	Q96DW6	Mitochondrial glycine transporter	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC25A38	Mitochondrial glycine transporter	Mitochondrial glycine transporter that imports glycine into the mitochondrial matrix.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC25A38	Other/Unknown	no		MCP_transmembrane, MCP_dom_sf, Hem25/SLC25A38

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	1
left lobe of thyroid gland	1
right lobe of thyroid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC25A38	267	ubiquitous	marker	body of pancreas, right lobe of thyroid gland, left lobe of thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC25A38	774

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC25A38	Q96DW6	82.91

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glycine import into mitochondrion	1	16852.0×	2e-04	SLC25A38
heme biosynthetic process	1	601.9×	0.002	SLC25A38
erythrocyte differentiation	1	267.5×	0.004	SLC25A38

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC25A38	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SLC25A38

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC25A38	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.