X-linked sideroblastic anemia with ataxia

Summary

X-linked sideroblastic anemia with ataxia (MONDO:0010524) is a disease caused by ABCB7 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ABCB7 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 29
• Phenotypes (HPO): 32

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		13	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

32 HPO clinical features (Orphanet curated; top 32 by frequency):

HPO ID	Term	Frequency
HP:0001251	Ataxia	Very frequent (80-99%)
HP:0001903	Anemia	Very frequent (80-99%)
HP:0002066	Gait ataxia	Very frequent (80-99%)
HP:0002167	Abnormality of speech or vocalization	Very frequent (80-99%)
HP:0012187	Increased erythrocyte protoporphyrin concentration	Very frequent (80-99%)
HP:0031936	Delayed ability to walk	Very frequent (80-99%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0001347	Hyperreflexia	Frequent (30-79%)
HP:0001348	Brisk reflexes	Frequent (30-79%)
HP:0001924	Sideroblastic anemia	Frequent (30-79%)
HP:0002172	Postural instability	Frequent (30-79%)
HP:0002194	Delayed gross motor development	Frequent (30-79%)
HP:0004840	Hypochromic microcytic anemia	Frequent (30-79%)
HP:0011273	Anisocytosis	Frequent (30-79%)
HP:0000717	Autism	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001272	Cerebellar atrophy	Occasional (5-29%)
HP:0001310	Dysmetria	Occasional (5-29%)
HP:0001510	Growth delay	Occasional (5-29%)
HP:0002075	Dysdiadochokinesis	Occasional (5-29%)
HP:0004447	Poikilocytosis	Occasional (5-29%)
HP:0020081	Pappenheimer bodies	Occasional (5-29%)
HP:0034499	Increased bone marrow iron	Occasional (5-29%)
HP:0000028	Cryptorchidism	Very rare (<1-4%)
HP:0000716	Depression	Very rare (<1-4%)
HP:0001250	Seizure	Very rare (<1-4%)
HP:0001992	Organic aciduria	Very rare (<1-4%)
HP:0100543	Cognitive impairment	Very rare (<1-4%)
HP:0100753	Schizophrenia	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	X-linked sideroblastic anemia with ataxia
Mondo ID	MONDO:0010524
MeSH	C536358
OMIM	301310
Orphanet	2802
DOID	DOID:0050554, DOID:0060064
SNOMED CT	719816006
UMLS	C1845028
MedGen	335078
GARD	0000668
Is cancer (heuristic)	no

Also known as: anaemia sideroblastic and spinocerebellar ataxia · anemia, Sex-linked hypochromic Siderobla · anemia, sideroblastic, and spinocerebellar ataxia · anemia, sideroblastic, with ataxia, X-linked recessive · ASAT · Pagon Bird Detter syndrome · Pagon-Bird-Detter syndrome · sideroblastic anaemia with spinocerebellar ataxia · sideroblastic anemia with spinocerebellar ataxia · X-linked sideroblastic Anaemia and ataxia · X-linked sideroblastic anaemia and spinocerebellar ataxia · X-linked sideroblastic anaemia with spinocerebellar ataxia · X-linked sideroblastic Anemia and ataxia · X-linked sideroblastic anemia with ataxia · X-linked sideroblastic anemia with spinocerebellar ataxia · XLSA-A · Xlsa-A

Data availability: 29 ClinVar variants · 7 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › X-linked disease › X-linked cerebellar ataxia › X-linked sideroblastic anemia with ataxia

Related subtypes (8): ataxia - deafness - intellectual disability syndrome, fragile X-associated tremor/ataxia syndrome, X-linked non progressive cerebellar ataxia, X-linked spinocerebellar ataxia type 3, X-linked spinocerebellar ataxia type 4, X-linked progressive cerebellar ataxia, spinocerebellar ataxia, X-linked 2, X-linked intellectual disability-ataxia-apraxia syndrome

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

29 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 5 benign, 4 pathogenic, 3 benign/likely benign, 3 likely pathogenic, 3 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
11574	NM_001271696.3(ABCB7):c.1200T>G (p.Ile400Met)	ABCB7	Pathogenic	criteria provided, single submitter
11575	NM_001271696.3(ABCB7):c.1297G>A (p.Glu433Lys)	ABCB7	Pathogenic	no assertion criteria provided
11576	NM_001271696.3(ABCB7):c.1231G>C (p.Val411Leu)	ABCB7	Pathogenic	no assertion criteria provided
126455	NM_001271696.3(ABCB7):c.624A>T (p.Glu208Asp)	ABCB7	Pathogenic	no assertion criteria provided
3235083	NM_001271696.3(ABCB7):c.1231G>T (p.Val411Leu)	ABCB7	Likely pathogenic	criteria provided, single submitter
3248639	NM_001271696.3(ABCB7):c.2021A>G (p.Asp674Gly)	ABCB7	Likely pathogenic	criteria provided, single submitter
372878	NM_001271696.3(ABCB7):c.1235T>C (p.Met412Thr)	ABCB7	Likely pathogenic	criteria provided, single submitter
368656	NM_001271696.3(ABCB7):c.1492G>A (p.Gly498Arg)	ABCB7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
368659	NM_001271696.3(ABCB7):c.168+13T>C	ABCB7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
914076	NM_001271696.3(ABCB7):c.1802A>G (p.Gln601Arg)	ABCB7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1333913	NM_001271696.3(ABCB7):c.2066C>T (p.Thr689Ile)	ABCB7	Uncertain significance	criteria provided, single submitter
2438737	NM_001271696.3(ABCB7):c.1106A>G (p.Lys369Arg)	ABCB7	Uncertain significance	criteria provided, single submitter
2582478	NM_001271696.3(ABCB7):c.358A>G (p.Ile120Val)	ABCB7	Uncertain significance	criteria provided, single submitter
368655	NM_001271696.3(ABCB7):c.1935+5G>C	ABCB7	Uncertain significance	criteria provided, multiple submitters, no conflicts
4077766	NM_001271696.3(ABCB7):c.2020G>A (p.Asp674Asn)	ABCB7	Uncertain significance	criteria provided, single submitter
814010	NM_001271696.3(ABCB7):c.1936-3C>G	ABCB7	Uncertain significance	criteria provided, single submitter
914074	NM_001271696.3(ABCB7):c.*113A>G	ABCB7	Uncertain significance	criteria provided, single submitter
914075	NM_001271696.3(ABCB7):c.2073T>C (p.His691=)	ABCB7	Uncertain significance	criteria provided, single submitter
914587	NM_001271696.3(ABCB7):c.1230A>G (p.Leu410=)	ABCB7	Uncertain significance	criteria provided, single submitter
914588	NM_001271696.3(ABCB7):c.1200T>C (p.Ile400=)	ABCB7	Uncertain significance	criteria provided, single submitter
976048	NM_001271696.3(ABCB7):c.944+3A>G	ABCB7	Uncertain significance	criteria provided, single submitter
1188878	NM_001271696.3(ABCB7):c.168+69C>G	ABCB7	Benign	criteria provided, multiple submitters, no conflicts
136242	NM_001271696.3(ABCB7):c.312C>T (p.Leu104=)	ABCB7	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
136243	NM_001271696.3(ABCB7):c.938G>A (p.Arg313Gln)	ABCB7	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
136244	NM_001271696.3(ABCB7):c.945-7C>T	ABCB7	Benign	criteria provided, multiple submitters, no conflicts
136245	NM_001271696.3(ABCB7):c.1739C>T (p.Ala580Val)	ABCB7	Benign	criteria provided, multiple submitters, no conflicts
368658	NM_001271696.3(ABCB7):c.1032+12A>G	ABCB7	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
559334	NM_001271696.3(ABCB7):c.201G>C (p.Gln67His)	ABCB7	Benign	criteria provided, multiple submitters, no conflicts
913727	NM_001271696.3(ABCB7):c.211A>G (p.Lys71Glu)	ABCB7	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
ABCB7	Definitive	X-linked	X-linked sideroblastic anemia with ataxia	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCB7	Orphanet:2802	X-linked sideroblastic anemia and spinocerebellar ataxia

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
ABCB7	HGNC:48	ENSG00000131269	O75027	Iron-sulfur clusters transporter ABCB7, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABCB7	Iron-sulfur clusters transporter ABCB7, mitochondrial	Exports glutathione-coordinated iron-sulfur clusters such as [2Fe-2S]-(GS)4 cluster from the mitochondria to the cytosol in an ATP-dependent manner allowing the assembly of the cytosolic iron-sulfur (Fe/S) cluster-containing proteins and p…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABCB7	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom

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
biceps brachii	1
gluteal muscle	1
triceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCB7	273	ubiquitous	marker	biceps brachii, gluteal muscle, triceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCB7	1,838

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCB7	O75027	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Mitochondrial ABC transporters	1	2855.0×	0.002	ABCB7
Cytosolic iron-sulfur cluster assembly	1	761.3×	0.003	ABCB7
ABC-family protein mediated transport	1	121.5×	0.014	ABCB7
Transport of small molecules	1	25.1×	0.050	ABCB7
Metabolism	1	11.6×	0.086	ABCB7

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
iron-sulfur cluster export from the mitochondrion	1	16852.0×	2e-04	ABCB7
positive regulation of iron-sulfur cluster assembly	1	16852.0×	2e-04	ABCB7
positive regulation of heme biosynthetic process	1	5617.3×	5e-04	ABCB7
iron ion transmembrane transport	1	2407.4×	8e-04	ABCB7
negative regulation of reactive oxygen species biosynthetic process	1	991.3×	0.002	ABCB7
iron-sulfur cluster assembly	1	601.9×	0.002	ABCB7
intracellular iron ion homeostasis	1	244.2×	0.005	ABCB7
transmembrane transport	1	168.5×	0.006	ABCB7

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCB7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ABCB7	1	Binding:1

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	1	ABCB7
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
ABCB7	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.