Leukopenia

Summary

Leukopenia (MONDO:0003785) is a disease with 2 cohort genes and 9 clinical trials. Top therapeutic interventions include fluconazole, luspatercept, and plerixafor.

At a glance

• Cohort genes: 2
• ClinVar variants: 3
• Clinical trials: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	leukopenia
Mondo ID	MONDO:0003785
MeSH	D007970
DOID	DOID:615
NCIT	C26816
SNOMED CT	84828003
UMLS	C0023530
MedGen	6073
Is cancer (heuristic)	no

Also known as: leukocytopenia · White blood cell decreased

Data availability: 3 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › immune system disorder › leukocyte disorder › leukopenia

Related subtypes (22): human monocytic ehrlichiosis, B cell deficiency, B-cell neoplasm, dendritic cell sarcoma, human granulocytic anaplasmosis, T-cell leukemia, phagocyte bactericidal dysfunction, EBV-positive T-cell lymphoproliferative disorder of childhood, small intestinal enteropathy-associated T-cell lymphoma, pituitary gland basophil adenoma, leukostasis, mastocytosis, hereditary neutrophilia, Pelger-Huet anomaly, functional neutrophil defect, thymoma type B, POEMS syndrome, Langerhans cell histiocytosis, subcutaneous panniculitis-like T-cell lymphoma, eosinophil peroxidase deficiency, eosinophil disorder, mast cell activation syndrome

Subtypes (2): agranulocytosis, lymphopenia

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

3 retrieved; paginated sample, class counts are floors:

1 likely pathogenic, 1 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
523274	GRCh37/hg19 22q11.21(chr22:18894835-21505417)	ARVCF	Pathogenic	criteria provided, single submitter
1174157	NM_020207.7:c.[2156delG];[3300_3303delTCAA]		Likely pathogenic	criteria provided, single submitter
68290	NM_001164277.2(SLC37A4):c.81T>A (p.Asn27Lys)	SLC37A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC37A4	Orphanet:79259	Glycogen storage disease due to glucose-6-phosphatase deficiency type Ib
ARVCF	Orphanet:567	22q11.2 deletion syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC37A4	HGNC:4061	ENSG00000137700	O43826	Glucose-6-phosphate exchanger SLC37A4	clinvar
ARVCF	HGNC:728	ENSG00000099889	O00192	Splicing regulator ARVCF	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC37A4	Glucose-6-phosphate exchanger SLC37A4	Inorganic phosphate and glucose-6-phosphate antiporter of the endoplasmic reticulum.
ARVCF	Splicing regulator ARVCF	Contributes to the regulation of alternative splicing of pre-mRNAs.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	38.9×	0.051
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC37A4	Transporter	yes		Sugar_P_transporter, MFS, MFS_dom
ARVCF	Other/Unknown	no		Armadillo, ARM-like, ARM-type_fold

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
duodenum	1
liver	1
right lobe of liver	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC37A4	134	ubiquitous	marker	right lobe of liver, liver, duodenum
ARVCF	273	ubiquitous	yes	cerebellar hemisphere, right hemisphere of cerebellum, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARVCF	1,392
SLC37A4	1,242

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC37A4	O43826	25

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ARVCF	O00192	65.73

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glucose-6-phosphate transport	1	1404.3×	0.006	SLC37A4
phosphate ion transmembrane transport	1	601.9×	0.007	SLC37A4
gluconeogenesis	1	162.0×	0.018	SLC37A4
glucose metabolic process	1	127.7×	0.018	SLC37A4
glucose homeostasis	1	65.3×	0.027	SLC37A4
cell-cell adhesion	1	50.8×	0.028	ARVCF
RNA splicing	1	44.1×	0.028	ARVCF
mRNA processing	1	39.4×	0.028	ARVCF
cell adhesion	1	18.7×	0.053	ARVCF

Therapeutics

Drugs indicated for this disease

0 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Fluconazole	Phase 3 (in late-stage trials)
Posaconazole	Phase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
SLC37A4	0	0
ARVCF	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
SLC37A4	5	Binding:5

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	SLC37A4
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ARVCF

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC37A4	5	—
ARVCF	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE3	1
PHASE1/PHASE2	1
PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00811928	PHASE3	COMPLETED	Safety and Efficacy Study of Posaconazole vs. Fluconazole for Prevention of Invasive Fungal Infection (P05387 AM1)(COMPLETED)
NCT00967785	PHASE1/PHASE2	RECRUITING	A Phase I Study of Mozobil in the Treatment of Patients With WHIMS
NCT06788691	PHASE2	RECRUITING	Luspatercept for Clonal Cytopenias of Uncertain Significance
NCT04283695	EARLY_PHASE1	UNKNOWN	To Investigate the Absorption, Metabolism, Excretion, Absolute Bioavailability, and Immunogenicity of GX-I7 in Healthy Volunteers
NCT06360952	Not specified	NOT_YET_RECRUITING	A Comparator Study of a Tasso Device Blood Sample to Traditional Venous Blood Sample for CBC
NCT07108023	Not specified	NOT_YET_RECRUITING	Hematological Disorders in EHPVO Patients
NCT00059423	Not specified	COMPLETED	Natural History Study for BEN
NCT01407484	Not specified	COMPLETED	Male Infertility Related With Post Infection Inflammatory Syndrome
NCT05225493	Not specified	UNKNOWN	HIV Indicator Diseases in Hospital and Primary Care

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLUCONAZOLE	4	1
LUSPATERCEPT	4	1
PLERIXAFOR	4	1
POSACONAZOLE	4	1