Pancytopenia

Summary

Pancytopenia (MONDO:0001529) is a disease with 6 cohort genes and 10 clinical trials. Top therapeutic interventions include alemtuzumab, nandrolone, and nandrolone cyclotate.

At a glance

• Cohort genes: 6
• ClinVar variants: 6
• Clinical trials: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pancytopenia
Mondo ID	MONDO:0001529
MeSH	D010198
DOID	DOID:12450
ICD-10-CM	D61.81
NCIT	C34889
SNOMED CT	127034005
UMLS	C0030312
MedGen	18281
Is cancer (heuristic)	no

Data availability: 6 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › pancytopenia

Related subtypes (18): congenital anemia, neonatal anemia, microcytic anemia, hypochromic anemia, deficiency anemia, pure red-cell aplasia, macrocytic anemia, normocytic anemia, sideroblastic anemia, aplastic anemia, hemoglobin C disease, hemoglobin E disease, beta-thalassemia and related diseases, hemoglobinopathy Toms River, hereditary methemoglobinemia, hemoglobin D disease, anemia due to enzyme disorder, anemia due to chronic disorder

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

6 retrieved; paginated sample, class counts are floors:

3 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 uncertain significance, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
942477	NM_000355.4(TCN2):c.428-2A>G	TCN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1174153	NM_020207.7:c.[3409_3410delAT];[3763C>T]		Likely pathogenic	criteria provided, single submitter
3233357	NM_001035006.5(RPL17):c.452del (p.Thr151fs)	RPL17	Likely pathogenic	criteria provided, single submitter
627081	NM_001754.5(RUNX1):c.502G>T (p.Gly168Ter)	RUNX1	Likely pathogenic	reviewed by expert panel
1065513	NM_001142864.4(PIEZO1):c.2610G>A (p.Met870Ile)	HSALR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1174155	NM_020207.7(ERCC6L2):c.1973G>A (p.Ser658Asn)	ERCC6L2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RUNX1	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
RUNX1	Orphanet:521	Chronic myeloid leukemia
RUNX1	Orphanet:71290	Familial platelet disorder with associated myeloid malignancy
RUNX1	Orphanet:98850	Aggressive systemic mastocytosis
TCN2	Orphanet:859	Transcobalamin deficiency
ERCC6L2	Orphanet:319465	Inherited acute myeloid leukemia
ERCC6L2	Orphanet:401764	Pancytopenia-developmental delay syndrome

Cohort genes → proteins

6 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPL17	HGNC:10307	ENSG00000265681	P18621	Large ribosomal subunit protein uL22	clinvar
RPL23	HGNC:10316	ENSG00000125691	P62829	Large ribosomal subunit protein uL14	clinvar
RUNX1	HGNC:10471	ENSG00000159216	Q01196	Runt-related transcription factor 1	clinvar
TCN2	HGNC:11653	ENSG00000185339	P20062	Transcobalamin-2	clinvar
ERCC6L2	HGNC:26922	ENSG00000182150	Q5T890	DNA excision repair protein ERCC-6-like 2	clinvar
HSALR1	HGNC:56095	ENSG00000224888		HSP90AB1 associated lncRNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPL17	Large ribosomal subunit protein uL22	Component of the large ribosomal subunit.
RPL23	Large ribosomal subunit protein uL14	Component of the large ribosomal subunit.
RUNX1	Runt-related transcription factor 1	Forms the heterodimeric complex core-binding factor (CBF) with CBFB.
TCN2	Transcobalamin-2	Primary vitamin B12-binding and transport protein.
ERCC6L2	DNA excision repair protein ERCC-6-like 2	Promotes double-strand break (DSB) end-joining and facilitates programmed recombination by controlling how DNA ends are joined in a spatially oriented manner during repair.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 5 · 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	5	1.5×	0.348
Transcription factor	1	1.4×	0.539

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPL17	Other/Unknown	no		Ribosomal_uL22, Ribosomal_uL22_euk_arc, Ribosomal_uL22_CS
RPL23	Other/Unknown	no		Ribosomal_uL14, Ribosomal_uL14_CS, Ribosomal_uL14_sf
RUNX1	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
TCN2	Other/Unknown	no		Cbl-bd_prot, Terpenoid_cyclase/PrenylTrfase, Cobalamin_Transport
ERCC6L2	Other/Unknown	no		SNF2_N, Helicase_C-like, DNA/RNA_helicase_DEAH_CS
HSALR1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

5 cohort genes 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left ovary	2
right ovary	2
ovary	1
ganglionic eminence	1
epithelium of bronchus	1
mucosa of paranasal sinus	1
olfactory segment of nasal mucosa	1
gall bladder	1
metanephros cortex	1
right lung	1
Brodmann (1909) area 23	1
endothelial cell	1
epithelial cell of pancreas	1
bone marrow cell	1
colonic epithelium	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPL17	134	ubiquitous	marker	left ovary, ovary, right ovary
RPL23	210	ubiquitous	marker	ganglionic eminence, left ovary, right ovary
RUNX1	253	ubiquitous	marker	olfactory segment of nasal mucosa, epithelium of bronchus, mucosa of paranasal sinus
TCN2	198	ubiquitous	marker	gall bladder, metanephros cortex, right lung
ERCC6L2	255	ubiquitous	marker	epithelial cell of pancreas, Brodmann (1909) area 23, endothelial cell
HSALR1	126		yes	colonic epithelium, bone marrow cell, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPL17	5,372
RUNX1	4,994
ERCC6L2	2,705
RPL23	1,303
TCN2	768
HSALR1	0

Structural data

PDB: 5 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPL17	P18621	195
RPL23	P62829	190
TCN2	P20062	11
RUNX1	Q01196	5
ERCC6L2	Q5T890	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 69. Enrichment computed across 6 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective TCN2 causes TCN2 deficiency	1	2855.0×	0.003	TCN2
Peptide chain elongation	2	63.4×	0.003	RPL17, RPL23
Viral mRNA Translation	2	63.4×	0.003	RPL17, RPL23
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	2	62.8×	0.003	RPL17, RPL23
Selenocysteine synthesis	2	60.1×	0.003	RPL17, RPL23
Eukaryotic Translation Termination	2	60.1×	0.003	RPL17, RPL23
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	2	58.9×	0.003	RPL17, RPL23
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	2	58.9×	0.003	RPL17, RPL23
Formation of a pool of free 40S subunits	2	56.0×	0.003	RPL17, RPL23
Response of EIF2AK4 (GCN2) to amino acid deficiency	2	55.4×	0.003	RPL17, RPL23
Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide	2	53.4×	0.003	RPL17, RPL23
L13a-mediated translational silencing of Ceruloplasmin expression	2	50.5×	0.003	RPL17, RPL23
SRP-dependent cotranslational protein targeting to membrane	2	50.1×	0.003	RPL17, RPL23
GTP hydrolysis and joining of the 60S ribosomal subunit	2	50.1×	0.003	RPL17, RPL23
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	2	48.8×	0.003	RPL17, RPL23
Defective CD320 causes MMATC	1	1427.5×	0.003	TCN2
RUNX3 regulates RUNX1-mediated transcription	1	951.7×	0.004	RUNX1
Regulation of expression of SLITs and ROBOs	2	34.6×	0.005	RPL17, RPL23
RUNX1 regulates expression of components of tight junctions	1	571.0×	0.005	RUNX1
RUNX1 regulates transcription of genes involved in interleukin signaling	1	571.0×	0.005	RUNX1
RUNX2 regulates genes involved in differentiation of myeloid cells	1	571.0×	0.005	RUNX1
Major pathway of rRNA processing in the nucleolus and cytosol	2	30.9×	0.005	RPL17, RPL23
RUNX1 regulates estrogen receptor mediated transcription	1	475.8×	0.006	RUNX1
RUNX1 regulates transcription of genes involved in BCR signaling	1	475.8×	0.006	RUNX1
RUNX1 regulates transcription of genes involved in WNT signaling	1	475.8×	0.006	RUNX1
RUNX1 regulates transcription of genes involved in differentiation of myeloid cells	1	356.9×	0.007	RUNX1
Transport of RCbl within the body	1	356.9×	0.007	TCN2
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	1	285.5×	0.008	RUNX1
RUNX1 regulates transcription of genes involved in differentiation of keratinocytes	1	285.5×	0.008	RUNX1
RUNX3 regulates p14-ARF	1	285.5×	0.008	RUNX1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of connective tissue replacement	1	3370.4×	0.005	RUNX1
myeloid leukocyte differentiation	1	1123.5×	0.005	RUNX1
regulation of plasminogen activation	1	1123.5×	0.005	RUNX1
protein-DNA complex disassembly	1	1123.5×	0.005	RPL23
negative regulation of CD4-positive, alpha-beta T cell differentiation	1	842.6×	0.005	RUNX1
cardiac muscle tissue regeneration	1	842.6×	0.005	RUNX1
positive regulation of extracellular matrix organization	1	842.6×	0.005	RUNX1
regulation of G1 to G0 transition	1	842.6×	0.005	RPL23
ribosomal protein import into nucleus	1	674.1×	0.005	RPL23
positive regulation of CD8-positive, alpha-beta T cell differentiation	1	674.1×	0.005	RUNX1
regulation of cardiac muscle cell proliferation	1	674.1×	0.005	RUNX1
cytoplasmic translation	2	74.1×	0.005	RPL17, RPL23
translation	2	41.1×	0.005	RPL17, RPL23
positive regulation of granulocyte differentiation	1	561.7×	0.005	RUNX1
cobalt ion transport	1	481.5×	0.006	TCN2
negative regulation of granulocyte differentiation	1	421.3×	0.006	RUNX1
cobalamin transport	1	374.5×	0.006	TCN2
double-strand break repair via classical nonhomologous end joining	1	337.0×	0.007	ERCC6L2
peripheral nervous system neuron development	1	306.4×	0.007	RUNX1
G1 to G0 transition	1	280.9×	0.007	RPL23
positive regulation of signal transduction by p53 class mediator	1	240.7×	0.008	RPL23
negative regulation of ubiquitin-dependent protein catabolic process	1	168.5×	0.011	RPL23
myeloid cell differentiation	1	129.6×	0.013	RUNX1
positive regulation of collagen biosynthetic process	1	129.6×	0.013	RUNX1
hematopoietic stem cell proliferation	1	129.6×	0.013	RUNX1
positive regulation of interleukin-2 production	1	93.6×	0.017	RUNX1
interstrand cross-link repair	1	86.4×	0.017	ERCC6L2
regulation of cell differentiation	1	86.4×	0.017	RUNX1
cellular response to reactive oxygen species	1	82.2×	0.017	ERCC6L2
chondrocyte differentiation	1	60.2×	0.023	RUNX1

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 6 evidence-associated genes (50%) 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
RPL17	GENTAMICIN SULFATE
RPL23	GENTAMICIN SULFATE
RUNX1	APOMORPHINE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RUNX1	2	4
RPL17	1	4
RPL23	1	4
TCN2	0	0
ERCC6L2	0	0
HSALR1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPL17, RPL23
APOMORPHINE HYDROCHLORIDE	4	RUNX1
MOLIBRESIB	2	RUNX1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RPL17	90	Binding:90
RPL23	90	Binding:90
RUNX1	20	Binding:17, Functional:3

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

3 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)
GENTAMICIN SULFATE	4	RPL17, RPL23
APOMORPHINE HYDROCHLORIDE	4	RUNX1
MOLIBRESIB	2	RUNX1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	RPL17, RPL23, RUNX1
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	3	TCN2, ERCC6L2, HSALR1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TCN2	0	—
ERCC6L2	0	—
HSALR1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 10.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4
PHASE1/PHASE2	2
PHASE1	2
PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00000597	PHASE3	COMPLETED	Multi-Center Trial of Anti-Thymocyte Globulin in Treatment of Aplastic Anemia and Other Hematologic Disorders
NCT00260689	PHASE2	COMPLETED	Three Immunosuppressive Treatment Regimens for Severe Aplastic Anemia
NCT01187017	PHASE1/PHASE2	COMPLETED	A Pilot Study of Fludarabine Plus Cyclophosphamide in Refractory Severe Aplastic Anemia
NCT01193283	PHASE1/PHASE2	COMPLETED	Cyclophosphamide Plus Cyclosporine in Treatment-Naive Severe Aplastic Anemia
NCT00001398	PHASE1	COMPLETED	Stem Cell Factor Medication for Aplastic Anemia
NCT00001399	PHASE1	COMPLETED	Gene Therapy for the Treatment of Fanconi’s Anemia Type C
NCT06999954	Not specified	RECRUITING	Shwachman-Diamond Syndrome Global Patient Survey and Partnering Platform
NCT00001214	Not specified	COMPLETED	Collection of Blood From Patients With Pancytopenia
NCT03521947	Not specified	UNKNOWN	Management of Childhood Pancytopenia
NCT05473650	Not specified	UNKNOWN	Spectrum of Hematological Disorders in Pediatrics

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ALEMTUZUMAB	4	1
NANDROLONE	3	1
NANDROLONE CYCLOTATE	2	1