Aplastic anemia

Summary

Aplastic anemia (MONDO:0015909) is a disease caused by PRF1 (GenCC Strong), with 10 cohort genes and 225 clinical trials. Top therapeutic interventions include cyclophosphamide anhydrous, romiplostim, and eltrombopag.

At a glance

• Causal gene: PRF1 (GenCC Strong)
• Cohort genes: 10
• ClinVar variants: 709
• Clinical trials: 225

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	aplastic anemia
Mondo ID	MONDO:0015909
MeSH	D000741
OMIM	609135
Orphanet	182040
DOID	DOID:12449
NCIT	C2870
SNOMED CT	306058006
UMLS	C0002874
MedGen	8063
GARD	0020234
Is cancer (heuristic)	no

Data availability: 709 ClinVar variants · 1 GenCC gene-disease record · 15 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

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

Related subtypes (18): congenital anemia, neonatal anemia, microcytic anemia, hypochromic anemia, pancytopenia, deficiency anemia, pure red-cell aplasia, macrocytic anemia, normocytic anemia, sideroblastic 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

Subtypes (4): inherited aplastic anemia, myelophthisic anemia, idiopathic aplastic anemia, acquired aplastic anemia

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

600 retrieved; paginated sample, class counts are floors:

198 uncertain significance, 120 pathogenic/likely pathogenic, 103 conflicting classifications of pathogenicity, 83 likely pathogenic, 43 pathogenic, 24 benign/likely benign, 16 benign, 9 likely benign, 4 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
523383	NM_000969.5(RPL5):c.74-1G>C	DIPK1A	Pathogenic	criteria provided, single submitter
39281	NR_001566.3(TERC):n.117A>C	LOC110806306	Pathogenic	no assertion criteria provided
39283	NR_001566.3(TERC):n.178G>A	LOC110806306	Pathogenic	no assertion criteria provided
39284	NR_001566.3(TERC):n.180C>T	LOC110806306	Pathogenic	no assertion criteria provided
39287	NR_001566.3(TERC):n.26_32delGGGTGGT	LOC110806306	Pathogenic	no assertion criteria provided
39289	NR_001566.3(TERC):n.305G>A	LOC110806306	Pathogenic	no assertion criteria provided
39290	NR_001566.3(TERC):n.322G>A	LOC110806306	Pathogenic	no assertion criteria provided
39291	NR_001566.3(TERC):n.323C>T	LOC110806306	Pathogenic	no assertion criteria provided
1367856	NM_002485.5(NBN):c.1889C>A (p.Ser630Ter)	LOC126860438	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142559	NM_002485.5(NBN):c.1903A>T (p.Lys635Ter)	LOC126860438	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370589	NM_002485.5(NBN):c.1848del (p.Glu617fs)	LOC126860438	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
492103	NM_002485.5(NBN):c.1882_1885del (p.Glu628fs)	LOC126860438	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068887	NM_002485.5(NBN):c.580G>T (p.Glu194Ter)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072146	NM_002485.5(NBN):c.2051del (p.Asn684fs)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073756	NM_002485.5(NBN):c.1106C>G (p.Ser369Ter)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075267	NM_002485.5(NBN):c.1234_1235del (p.Ser411_Asn412insTer)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075847	NM_002485.5(NBN):c.4del (p.Trp2fs)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1171345	NM_002485.5(NBN):c.217A>T (p.Lys73Ter)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1244220	NM_002485.5(NBN):c.1147G>T (p.Glu383Ter)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
127878	NM_002485.5(NBN):c.698_701del (p.Lys233fs)	NBN	Pathogenic	criteria provided, multiple submitters, no conflicts
1353264	NM_002485.5(NBN):c.1837A>T (p.Lys613Ter)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1369725	NM_002485.5(NBN):c.1225del (p.Thr409fs)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1369995	NM_002485.5(NBN):c.1523dup (p.Ser509fs)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1387838	NM_002485.5(NBN):c.278C>A (p.Ser93Ter)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
140828	NM_002485.5(NBN):c.306del (p.Phe102fs)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141631	NM_002485.5(NBN):c.123del (p.Ser42fs)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141731	NM_002485.5(NBN):c.1142del (p.Pro381fs)	NBN	Pathogenic	criteria provided, multiple submitters, no conflicts
141946	NM_002485.5(NBN):c.1474C>T (p.Gln492Ter)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451838	NM_002485.5(NBN):c.2071del	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1452434	NM_002485.5(NBN):c.14_23del (p.Leu5fs)	NBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 30 · 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
PRF1	Strong	Autosomal recessive	aplastic anemia	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRF1	Orphanet:391343	Fatal post-viral neurodegenerative disorder
PRF1	Orphanet:540	Familial hemophagocytic lymphohistiocytosis
PRF1	Orphanet:88	Idiopathic aplastic anemia
TERC	Orphanet:1775	Dyskeratosis congenita
TERC	Orphanet:2032	Idiopathic pulmonary fibrosis
TERC	Orphanet:88	Idiopathic aplastic anemia
TERT	Orphanet:146	Differentiated thyroid carcinoma
TERT	Orphanet:1501	Adrenocortical carcinoma
TERT	Orphanet:1775	Dyskeratosis congenita
TERT	Orphanet:2032	Idiopathic pulmonary fibrosis
TERT	Orphanet:2495	Meningioma
TERT	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
TERT	Orphanet:457246	Clear cell sarcoma of kidney
TERT	Orphanet:618	Familial melanoma
TERT	Orphanet:88	Idiopathic aplastic anemia
TINF2	Orphanet:1775	Dyskeratosis congenita
TINF2	Orphanet:3088	Revesz syndrome
TINF2	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
DDX41	Orphanet:488647	DDX41-related hematologic malignancy predisposition syndrome
SBDS	Orphanet:622934	SBDS-related severe neonatal spondylometaphyseal dysplasia
SBDS	Orphanet:811	Shwachman-Diamond syndrome
SBDS	Orphanet:88	Idiopathic aplastic anemia
FANCM	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
FANCM	Orphanet:84	Fanconi anemia
IFNG	Orphanet:699618	Severe mendelian susceptibility to mycobacterial diseases due to complete IFNG deficiency
IFNG	Orphanet:805	Tuberous sclerosis complex
IFNG	Orphanet:88	Idiopathic aplastic anemia
NBN	Orphanet:1331	Familial prostate cancer
NBN	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
NBN	Orphanet:647	Nijmegen breakage syndrome

Cohort genes → proteins

10 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PRF1	HGNC:9360	ENSG00000180644	P14222	Perforin-1	gencc,clinvar
TERC	HGNC:11727	ENSG00000270141		telomerase RNA component	clinvar
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	clinvar
TINF2	HGNC:11824	ENSG00000092330	Q9BSI4	TERF1-interacting nuclear factor 2	clinvar
DDX41	HGNC:18674	ENSG00000183258	Q9UJV9	Probable ATP-dependent RNA helicase DDX41	clinvar
SBDS	HGNC:19440	ENSG00000126524	Q9Y3A5	Ribosome maturation protein SBDS	clinvar
FANCM	HGNC:23168	ENSG00000187790	Q8IYD8	Fanconi anemia group M protein	clinvar
DIPK1A	HGNC:32213	ENSG00000154511	Q5T7M9	Divergent protein kinase domain 1A	clinvar
IFNG	HGNC:5438	ENSG00000111537	P01579	Interferon gamma	clinvar
NBN	HGNC:7652	ENSG00000104320	O60934	Nibrin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRF1	Perforin-1	Pore-forming protein that plays a key role in granzyme-mediated programmed cell death, and in defense against virus-infected or neoplastic cells.
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
TINF2	TERF1-interacting nuclear factor 2	Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection.
DDX41	Probable ATP-dependent RNA helicase DDX41	Multifunctional protein that participates in many aspects of cellular RNA metabolism.
SBDS	Ribosome maturation protein SBDS	Required for the assembly of mature ribosomes and ribosome biogenesis.
FANCM	Fanconi anemia group M protein	DNA-dependent ATPase component of the Fanconi anemia (FA) core complex.
IFNG	Interferon gamma	Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation.
NBN	Nibrin	Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 8 · Druggable fraction: 0.2

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
Complement	1	26.8×	0.110
Other/Unknown	8	1.4×	0.163
Kinase	1	2.8×	0.308

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRF1	Complement	yes		C2_dom, MACPF_CS, MACPF
TERC	Other/Unknown	no
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
TINF2	Other/Unknown	no		TINF2_N, TINF2
DDX41	Other/Unknown	no		Helicase_C-like, DEAD/DEAH_box_helicase_dom, Helicase_ATP-bd
SBDS	Other/Unknown	no		Sdo1/SBDS, Ribosome_mat_SBDS_CS, SDO1/SBDS_central
FANCM	Other/Unknown	no		Helicase_C-like, ERCC4_domain, RuvA_2-like
DIPK1A	Kinase	yes		FAM69_kinase_dom, FAM69_N
IFNG	Other/Unknown	no		Interferon_gamma, 4_helix_cytokine-like_core
NBN	Other/Unknown	no		FHA_dom, BRCT_dom, SMAD_FHA_dom_sf

Expression context

Cohort genes with no expression data: 0.

8 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)	10
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	4
male germ line stem cell (sensu Vertebrata) in testis	3
blood	1
spleen	1
bone marrow cell	1
colonic epithelium	1
olfactory bulb	1
stromal cell of endometrium	1
type B pancreatic cell	1
right adrenal gland	1
right adrenal gland cortex	1
lower esophagus mucosa	1
right frontal lobe	1
calcaneal tendon	1
popliteal artery	1
tibial artery	1
oocyte	1
sperm	1
Brodmann (1909) area 23	1
endothelial cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRF1	220	broad	marker	granulocyte, blood, spleen
TERC	113	ubiquitous	yes	bone marrow cell, colonic epithelium, male germ line stem cell (sensu Vertebrata) in testis
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
TINF2	144	ubiquitous	marker	granulocyte, right adrenal gland, right adrenal gland cortex
DDX41	274	ubiquitous	marker	granulocyte, right frontal lobe, lower esophagus mucosa
SBDS	144	ubiquitous	marker	popliteal artery, tibial artery, calcaneal tendon
FANCM	203	ubiquitous	marker	sperm, oocyte, male germ line stem cell (sensu Vertebrata) in testis
DIPK1A	275	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, middle temporal gyrus
IFNG	119	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, granulocyte, lymph node
NBN	299	ubiquitous	marker	endometrium epithelium, mammary duct, cauda epididymis

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFNG	7,383
TERT	5,717
PRF1	3,299
FANCM	2,764
DDX41	2,388
SBDS	2,110
NBN	1,989
TINF2	1,769
DIPK1A	575
TERC	0

Intra-cohort edges

A	B	Sources
IFNG	PRF1	string_interaction
SBDS	TERT	string_interaction
TERT	TINF2	string_interaction

Structural data

PDB: 7 · AlphaFold-only: 2 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TERT	O14746	23
IFNG	P01579	8
FANCM	Q8IYD8	7
NBN	O60934	7
SBDS	Q9Y3A5	6
DDX41	Q9UJV9	5
TINF2	Q9BSI4	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRF1	P14222	91.01
DIPK1A	Q5T7M9	83.20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 81. Enrichment computed across 10 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Telomere Extension By Telomerase	2	130.5×	0.008	TERT, TINF2
DNA Damage/Telomere Stress Induced Senescence	2	46.6×	0.031	TINF2, NBN
Sensing of DNA Double Strand Breaks	1	271.9×	0.041	NBN
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	233.1×	0.041	TERT
IFNG signaling activates MAPKs	1	203.9×	0.041	IFNG
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	1	163.1×	0.041	IFNG
STING mediated induction of host immune responses	1	148.3×	0.041	DDX41
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	135.9×	0.041	NBN
HDR through MMEJ (alt-NHEJ)	1	125.5×	0.041	NBN
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)	1	125.5×	0.041	IFNG
Telomere C-strand synthesis initiation	1	116.5×	0.041	TINF2
IRF3-mediated induction of type I IFN	1	116.5×	0.041	DDX41
Regulation of IFNG signaling	1	116.5×	0.041	IFNG
Diseases of DNA Double-Strand Break Repair	1	116.5×	0.041	NBN
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	116.5×	0.041	NBN
Processive synthesis on the C-strand of the telomere	1	108.8×	0.041	TINF2
Telomere C-strand (Lagging Strand) Synthesis	1	108.8×	0.041	TINF2
Regulation of innate immune responses to cytosolic DNA	1	108.8×	0.041	DDX41
Removal of the Flap Intermediate from the C-strand	1	90.6×	0.044	TINF2
Resolution of D-Loop Structures	1	90.6×	0.044	NBN
Extension of Telomeres	1	85.9×	0.045	TERT
Diseases of DNA repair	1	81.6×	0.045	NBN
DNA Double Strand Break Response	1	68.0×	0.046	NBN
Impaired BRCA2 binding to PALB2	1	65.3×	0.046	NBN
Polymerase switching on the C-strand of the telomere	1	60.4×	0.046	TINF2
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	60.4×	0.046	NBN
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	60.4×	0.046	NBN
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	60.4×	0.046	NBN
Cell Cycle	2	10.3×	0.046	TERT, NBN
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	56.3×	0.048	NBN

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
RNA-templated transcription	1	2106.5×	0.008	TERT
DNA strand elongation	1	2106.5×	0.008	TERT
positive regulation of killing of cells of another organism	1	2106.5×	0.008	PRF1
positive regulation of fructose 1,6-bisphosphate metabolic process	1	2106.5×	0.008	IFNG
siRNA transcription	1	2106.5×	0.008	TERT
positive regulation of transdifferentiation	1	2106.5×	0.008	TERT
regulation of telomere maintenance via telomere lengthening	1	2106.5×	0.008	TINF2
positive regulation of telomere maintenance	2	127.7×	0.008	TINF2, NBN
telomere maintenance	2	66.9×	0.008	TERT, NBN
defense response to virus	3	26.0×	0.008	PRF1, DDX41, IFNG
RNA-templated DNA biosynthetic process	1	1053.2×	0.008	TERT
obsolete positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation involved in immune response	1	1053.2×	0.008	IFNG
positive regulation of peptidyl-serine phosphorylation of STAT protein	1	1053.2×	0.008	IFNG
positive regulation of hair cycle	1	1053.2×	0.008	TERT
positive regulation of vitamin D biosynthetic process	1	1053.2×	0.008	IFNG
telomere maintenance via telomere trimming	1	1053.2×	0.008	NBN
positive regulation of iron ion import across plasma membrane	1	1053.2×	0.008	IFNG
positive regulation of tumor necrosis factor (ligand) superfamily member 11 production	1	1053.2×	0.008	IFNG
immune response to tumor cell	1	702.2×	0.012	PRF1
telomeric 3’ overhang formation	1	526.6×	0.014	NBN
telomere assembly	1	526.6×	0.014	TINF2
double-strand break repair via synthesis-dependent strand annealing	1	526.6×	0.014	FANCM
apoptotic process	3	10.8×	0.014	PRF1, DDX41, IFNG
cGAS/STING signaling pathway	1	421.3×	0.015	DDX41
positive regulation of protein monoubiquitination	1	421.3×	0.015	FANCM
negative regulation of telomere capping	1	421.3×	0.015	NBN
blastocyst growth	1	351.1×	0.016	NBN
positive regulation of protein localization to nucleolus	1	351.1×	0.016	TERT
protection from non-homologous end joining at telomere	1	300.9×	0.017	NBN
positive regulation of interleukin-23 production	1	300.9×	0.017	IFNG

Therapeutics

Drugs indicated for this disease

4 approved, 8 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Cortisone Acetate	Approved (phase 4)
Dexamethasone	Approved (phase 4)
Prednisolone	Approved (phase 4)
Prednisone	Approved (phase 4)
Cyclosporine	Phase 3 (in late-stage trials)
Eltrombopag	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Fludarabine	Phase 3 (in late-stage trials)
Fludarabine Phosphate	Phase 3 (in late-stage trials)
Hetrombopag Olamine	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Nandrolone	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Alemtuzumab, Avatrombopag, Daclizumab, Decitabine, Levamisole, Luspatercept, Melphalan, Methylprednisolone, Motixafortide, Mycophenolate Mofetil, Pegfilgrastim, Rafutrombopag, Recombinant Human Thrombopoietin, Rituximab, Romiplostim, Sirolimus, Tacrolimus Anhydrous.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 8

Druggability breadth: 6 of 10 evidence-associated genes (60%) 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
TERT	BERBERINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TERT	10	4
DDX41	1	2
PRF1	0	0
TERC	0	0
TINF2	0	0
SBDS	0	0
FANCM	0	0
DIPK1A	0	0
IFNG	0	0
NBN	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
RESVERATROL	3	TERT
EPIGALOCATECHIN GALLATE	3	TERT
PERIFOSINE	3	TERT
ISOMETAMIDIUM	2	TERT
HOMIDIUM BROMIDE	2	TERT
ALLICIN	2	TERT
OLEIC ACID	2	TERT
ETHACRIDINE	2	TERT
MOLIBRESIB	2	DDX41

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TERT	391	Binding:389, Functional:2
PRF1	34	Binding:34
DDX41	7	Binding:7
NBN	2	Binding:2
SBDS	1	Binding:1
IFNG	1	Binding:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TERT	391

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

11 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)
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
RESVERATROL	3	TERT
EPIGALOCATECHIN GALLATE	3	TERT
PERIFOSINE	3	TERT
ISOMETAMIDIUM	2	TERT
HOMIDIUM BROMIDE	2	TERT
ALLICIN	2	TERT
OLEIC ACID	2	TERT
ETHACRIDINE	2	TERT
MOLIBRESIB	2	DDX41

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TERT
B	Phased (≥1) drug, not yet approved	1	DDX41
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	2	PRF1, DIPK1A
E	Difficult family or no structure, no drug	6	TERC, TINF2, SBDS, FANCM, IFNG, NBN

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PRF1	34	—
TERC	0	—
TINF2	0	—
SBDS	1	—
FANCM	0	—
DIPK1A	0	—
IFNG	1	—
NBN	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 225.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	81
Not specified	68
PHASE1/PHASE2	26
PHASE4	17
PHASE1	13
PHASE3	9
PHASE2/PHASE3	7
EARLY_PHASE1	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06424639	PHASE4	NOT_YET_RECRUITING	Luspatercept Plus CsA vs CsA for the Treatment of Newly Diagnosed Non-Transfusion-Dependent NSAA
NCT06426043	PHASE4	NOT_YET_RECRUITING	A Prospective Study on the Treatment of Recurrent/Refractory/Intolerable NSAA With Lusutrombopag
NCT06516484	PHASE4	NOT_YET_RECRUITING	Ropustin for Refractory Aplastic Anaemia After Radiotherapy - a Single-centre, Prospective, Open-label, Single-arm Study
NCT06525948	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of rhTPO in Combination With Cyclosporine Versus Cyclosporine Alone in the Treatment of TD-NSAA
NCT06535685	PHASE4	NOT_YET_RECRUITING	A Study of Romiplostim for the Treatment of Refractory Transfusion-dependent NSAA
NCT01818726	PHASE4	TERMINATED	Safety and Efficacy of Exjade in the Treatment of Transfusion-dependent Iron Overload in Aplastic Anemia Patients
NCT01995331	PHASE4	UNKNOWN	Moderate-dose Cyclophosphamide for Childhood Acquired Aplastic Anemia
NCT01997372	PHASE4	UNKNOWN	Different Doses of Anti-thymocyte Globin to Treat Child Severe Aplastic Anemia
NCT02745717	PHASE4	COMPLETED	The Efficacy of Immunosuppressive Therapy Combined With Cord Blood Transfusion in Treatment of Severe Aplastic Anemia
NCT02838992	PHASE4	UNKNOWN	ATG Combined With Cyclophosphamide And Cord Blood Transfusion in Treating Patients With Severe Aplastic Anemia
NCT02875743	PHASE4	COMPLETED	King’s Invasive Aspergillosis Study II
NCT03176849	PHASE4	COMPLETED	A Randomized Phase IV Control Trial of Single High Dose Oral Vitamin D3 in Pediatric Patients Undergoing HSCT
NCT03896971	PHASE4	COMPLETED	Combination of Thrombopoietin Mimetic and Immunosuppressive Therapy in Aplastic Anaemia
NCT05996393	PHASE4	COMPLETED	CsA+ATG+AVA vs. CsA+AVA for the Treatment of Newly-diagnosed SAA in the Elderly
NCT06004791	PHASE4	UNKNOWN	A Prospective, Randomized, Controlled Study of rhTPO in Combination With Herombopag + CsA vs Herombopag + CsA for the Treatment of Primary TD-NSAA
NCT06009965	PHASE4	UNKNOWN	Efficacy of IST Combined With TPO-RA in the Treatment of AA and Establishment of a Recurrence Prediction System
NCT06069180	PHASE4	UNKNOWN	The Optimization of Conditioning Regimen for HLA Matched HSCT in SAA
NCT05600426	PHASE3	ACTIVE_NOT_RECRUITING	A Trial Comparing Unrelated Donor BMT With IST for Pediatric and Young Adult Patients With Severe Aplastic Anemia (TransIT, BMT CTN 2202)
NCT07001397	PHASE3	NOT_YET_RECRUITING	Study on the Short-term Efficacy and Safety of Recombinant Human Thrombopoietin Combined With Immunosuppressant Sequential Eltrombopag Ethanolamine Dry Suspension in the Treatment of SAA/TD-NSAA
NCT00004474	PHASE3	COMPLETED	Phase III Randomized Study of Cyclophosphamide With or Without Antithymocyte Globulin Before Bone Marrow Transplantation in Patients With Aplastic Anemia
NCT00455312	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant (SCT) for Dyskeratosis Congenita or SAA
NCT01145976	PHASE3	UNKNOWN	Comparison of Cy-Atg vs Flu-Atg for the Conditioning Therapy in Allo-HCT for Adult Aplastic Anemia
NCT01343680	PHASE3	TERMINATED	Trial of Two Central Venous Catheter (CVC) Flushing Schemes in Pediatric Hematology and Oncology Patients
NCT02099747	PHASE3	COMPLETED	hATG+CsA vs hATG+CsA+Eltrombopag for SAA
NCT02773290	PHASE2/PHASE3	COMPLETED	Study of Romiplostim(AMG531) in Subjects With Aplastic Anemia
NCT03295058	PHASE2/PHASE3	UNKNOWN	Peripheral Blood Allogenic Stem Cell Transplantation Using Non-anti Thymocyte Globulin Regimens in Severe Aplastic Anemia Patients
NCT03825744	PHASE3	COMPLETED	Hetrombopag or Placebo in Treatment-Naive Severe Aplastic Anemia
NCT03957694	PHASE2/PHASE3	COMPLETED	Study of AMG531(Romiplostim) in Patients With Aplastic Anemia
NCT04095936	PHASE2/PHASE3	COMPLETED	Study of AMG531 (Romiplostim) in Patients With Aplastic Anemia
NCT04350606	PHASE3	COMPLETED	A Study to Assess Efficacy and Safety of PF-06462700 in Japanese Participants With Aplastic Anemia
NCT04728789	PHASE2/PHASE3	UNKNOWN	Avatrombopag Usage in NSAA
NCT05018936	PHASE2/PHASE3	UNKNOWN	Efficacy and Safety of Hetrombopag in Non-severe Aplastic Anemia
NCT06940570	PHASE3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT01174108	PHASE2	RECRUITING	Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes Using G-CSF Mobilized CD34+ Selected Hematopoietic Precursor Cells Co-Infused With a Reduced Dose of Non-Mobilized Donor T-cells
NCT01623167	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Eltrombopag With Standard Immunosuppression for Severe Aplastic Anemia
NCT01624805	PHASE2	RECRUITING	Methylprednisolone, Horse Anti-Thymocyte Globulin, Cyclosporine, Filgrastim, and/or Pegfilgrastim or Pegfilgrastim Biosimilar in Treating Patients With Aplastic Anemia or Low or Intermediate-Risk Myelodysplastic Syndrome
NCT01659606	PHASE2	ACTIVE_NOT_RECRUITING	Radiation- and Alkylator-free Bone Marrow Transplantation Regimen for Patients With Dyskeratosis Congenita
NCT01966367	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation
NCT02828592	PHASE2	RECRUITING	Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia
NCT02979873	PHASE2	ACTIVE_NOT_RECRUITING	Sirolimus (Rapamune ) for Relapse Prevention in People With Severe Aplastic Anemia Responsive to Immunosuppressive Therapy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CYCLOPHOSPHAMIDE ANHYDROUS	4	34
ROMIPLOSTIM	4	10
ELTROMBOPAG	4	8
AVATROMBOPAG	4	6
CYCLOSPORINE	4	6
2-MERCAPTOETHANESULFONIC ACID	4	4
LUSPATERCEPT	4	2
POSACONAZOLE	4	2
ALEMTUZUMAB	4	1
BUSULFAN	4	1
CLOFARABINE	4	1
DACLIZUMAB	4	1
DANAZOL	4	1
DEFERASIROX	4	1
FLUDARABINE PHOSPHATE	4	1
LEVAMISOLE	4	1
LUSUTROMBOPAG	4	1
MELPHALAN	4	1
NANDROLONE DECANOATE	4	1
FLUDARABINE	3	2
HETROMBOPAG OLAMINE	3	2
RAFUTROMBOPAG	3	2
MOTIXAFORTIDE	3	1
ANTILYMPHOCYTE IMMUNOGLOBULIN (HORSE)	2	3
DEXAMISOLE	2	1
CHEMBL406352	0	2
CHEMBL290077	0	2