Megaloblastic anemia, folate-responsive

Summary

Megaloblastic anemia, folate-responsive (MONDO:0011141) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	megaloblastic anemia, folate-responsive
Mondo ID	MONDO:0011141
OMIM	601775
UMLS	C2749656
MedGen	440842
GARD	0027127
Is cancer (heuristic)	no

Also known as: folate level in erythrocytes · MEGAF

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › disorder of metabolite absorption and transport › disorder of vitamin and non-protein cofactor absorption and transport › disorder of folate metabolism and transport › megaloblastic anemia-immunodeficiency due to folate transporter 1 deficiency › megaloblastic anemia, folate-responsive

Related subtypes (1): immunodeficiency 114, folate-responsive

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

2 retrieved; paginated sample, class counts are floors:

2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1054650	NM_194255.4(SLC19A1):c.631TTC[1] (p.Phe212del)	SLC19A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2798991	NM_194255.4(SLC19A1):c.136A>T (p.Ser46Cys)	SLC19A1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
SLC19A1	Limited	Autosomal recessive	megaloblastic anemia, folate-responsive	2

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
SLC19A1	HGNC:10937	ENSG00000173638	P41440	Reduced folate transporter	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC19A1	Reduced folate transporter	Antiporter that mediates the import of reduced folates or a subset of cyclic dinucleotides, driven by the export of organic anions.

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)
SLC19A1	Transporter	yes		Folate_carrier, SLC19A1, MFS_trans_sf

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
blood	1
endothelial cell	1
jejunal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC19A1	238	ubiquitous	marker	jejunal mucosa, blood, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC19A1	1,161

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC19A1	P41440	19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Metabolism of folate and pterines	1	634.4×	0.006	SLC19A1
Metabolism of water-soluble vitamins and cofactors	1	181.3×	0.011	SLC19A1
Metabolism of vitamins and cofactors	1	116.5×	0.011	SLC19A1
Metabolism	1	11.6×	0.086	SLC19A1

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
methotrexate transport	1	8426.0×	0.001	SLC19A1
folate transmembrane transport	1	4213.0×	0.001	SLC19A1
folate import across plasma membrane	1	4213.0×	0.001	SLC19A1
folic acid transport	1	2808.7×	0.001	SLC19A1
cyclic-GMP-AMP transmembrane import across plasma membrane	1	2106.5×	0.001	SLC19A1
positive regulation of cGAS/STING signaling pathway	1	2106.5×	0.001	SLC19A1
folic acid metabolic process	1	1123.5×	0.002	SLC19A1
xenobiotic transmembrane transport	1	936.2×	0.002	SLC19A1
obsolete organic anion transport	1	802.5×	0.002	SLC19A1
female pregnancy	1	210.7×	0.006	SLC19A1
response to toxic substance	1	210.7×	0.006	SLC19A1
transport across blood-brain barrier	1	179.3×	0.006	SLC19A1
response to xenobiotic stimulus	1	69.1×	0.014	SLC19A1

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SLC19A1	PRALATREXATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC19A1	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PRALATREXATE	4	SLC19A1
RALTITREXED	4	SLC19A1
PEMETREXED	4	SLC19A1
METHOTREXATE	4	SLC19A1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC19A1	18	Binding:18

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

4 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.

Compound	Max phase	Cohort target (bioactivity)
PRALATREXATE	4	SLC19A1
RALTITREXED	4	SLC19A1
PEMETREXED	4	SLC19A1
METHOTREXATE	4	SLC19A1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SLC19A1
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.