Diamond-Blackfan anemia

Summary

Diamond-Blackfan anemia (MONDO:0015253) is a disease (an umbrella term covering 22 Mondo subtypes) caused by variants in RPS10, RPS19, RPS24, and 2 other genes, with 40 cohort genes and 38 clinical trials. The dominant Reactome pathway is Peptide chain elongation (22 cohort genes). Top therapeutic interventions include fludarabine phosphate, busulfan, and deferasirox.

At a glance

• Prevalence: 1-9 / 1 000 000 (China) [Orphanet-validated]
• Causal genes: RPS10 (GenCC Definitive), RPS19 (GenCC Definitive), RPS24 (GenCC Definitive), GATA1 (GenCC Strong) (+1 more)
• Umbrella term: 22 Mondo subtypes
• Cohort genes: 40
• ClinVar variants: 1,435
• Phenotypes (HPO): 59
• Clinical trials: 38

Clinical features

Epidemiology

Prevalence records

5 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 1 000 000	0.67	Europe	Validated
Point prevalence	1-9 / 1 000 000	0.194	China	Validated
Prevalence at birth	1-9 / 1 000 000	0.5	United Kingdom	Validated
Prevalence at birth	1-9 / 1 000 000	0.65	Italy	Validated
Prevalence at birth	1-9 / 1 000 000	0.75	United States	Validated

Signs & symptoms

Clinical features (HPO)

59 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0012410	Pure red cell aplasia	Very frequent (80-99%)
HP:0030270	Elevated red cell adenosine deaminase activity	Very frequent (80-99%)
HP:0000234	Abnormality of the head	Frequent (30-79%)
HP:0000980	Pallor	Frequent (30-79%)
HP:0001254	Lethargy	Frequent (30-79%)
HP:0001510	Growth delay	Frequent (30-79%)
HP:0001518	Small for gestational age	Frequent (30-79%)
HP:0001896	Reticulocytopenia	Frequent (30-79%)
HP:0005518	Increased mean corpuscular volume	Frequent (30-79%)
HP:0005532	Macrocytic dyserythropoietic anemia	Frequent (30-79%)
HP:0011904	Persistence of hemoglobin F	Frequent (30-79%)
HP:0012133	Erythroid hypoplasia	Frequent (30-79%)
HP:0000047	Hypospadias	Occasional (5-29%)
HP:0000085	Horseshoe kidney	Occasional (5-29%)
HP:0000104	Renal agenesis	Occasional (5-29%)
HP:0000119	Abnormality of the genitourinary system	Occasional (5-29%)
HP:0000185	Cleft soft palate	Occasional (5-29%)
HP:0000218	High palate	Occasional (5-29%)
HP:0000465	Webbed neck	Occasional (5-29%)
HP:0000470	Short neck	Occasional (5-29%)
HP:0000912	Sprengel anomaly	Occasional (5-29%)
HP:0001199	Triphalangeal thumb	Occasional (5-29%)
HP:0001227	Abnormality of the thenar eminence	Occasional (5-29%)
HP:0001627	Abnormal heart morphology	Occasional (5-29%)
HP:0001629	Ventricular septal defect	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001882	Leukopenia	Occasional (5-29%)
HP:0001895	Normochromic anemia	Occasional (5-29%)
HP:0002817	Abnormality of the upper limb	Occasional (5-29%)
HP:0002863	Myelodysplasia	Occasional (5-29%)
HP:0004322	Short stature	Occasional (5-29%)
HP:0009777	Absent thumb	Occasional (5-29%)
HP:0009778	Short thumb	Occasional (5-29%)
HP:0009944	Partial duplication of thumb phalanx	Occasional (5-29%)
HP:0012758	Neurodevelopmental delay	Occasional (5-29%)
HP:0020118	Radial artery aplasia	Occasional (5-29%)
HP:0410030	Cleft lip	Occasional (5-29%)
HP:0000252	Microcephaly	Very rare (<1-4%)
HP:0000286	Epicanthus	Very rare (<1-4%)
HP:0000294	Low anterior hairline	Very rare (<1-4%)
HP:0000316	Hypertelorism	Very rare (<1-4%)
HP:0000347	Micrognathia	Very rare (<1-4%)
HP:0000369	Low-set ears	Very rare (<1-4%)
HP:0000431	Wide nasal bridge	Very rare (<1-4%)
HP:0000486	Strabismus	Very rare (<1-4%)
HP:0000508	Ptosis	Very rare (<1-4%)
HP:0000519	Developmental cataract	Very rare (<1-4%)
HP:0001087	Developmental glaucoma	Very rare (<1-4%)
HP:0001680	Coarctation of aorta	Very rare (<1-4%)
HP:0001790	Nonimmune hydrops fetalis	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Diamond-Blackfan anemia
Mondo ID	MONDO:0015253
MeSH	D029503
OMIM	105650
Orphanet	124
DOID	DOID:1339
NCIT	C61236
SNOMED CT	88854002
UMLS	C1260899
MedGen	266045
GARD	0006274
MedDRA	10062989
NORD	773
Is cancer (heuristic)	no

Also known as: Aase syndrome · Aase-Smith II syndrome · anaemia congenital erythroid hypoplastic · anaemia Diamond Blackfan type · anemia congenital erythroid hypoplastic · anemia Diamond Blackfan type · aregenerative anaemia chronic congenital · aregenerative anemia chronic congenital · BDS · Blackfan Diamond syndrome · Blackfan-Diamond anaemia · Blackfan-Diamond anemia · chronic constitutional pure red cell anemia · congenital hypoplastic anaemia · congenital hypoplastic anemia · congenital hypoplastic anemia, Blackfan-Diamond type · congenital PRCA · congenital pure red cell aplasia · DBA · Diamond Blackfan Anemia (+4 more)

Data availability: 1,435 ClinVar variants · 32 GenCC gene-disease records · 17 cell lines.

Disease family

An umbrella term covering 22 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › pure red-cell aplasia › Diamond-Blackfan anemia

Related subtypes (1): adult pure red cell aplasia

Subtypes (22): Diamond-Blackfan anemia 1, Diamond-Blackfan anemia 14 with mandibulofacial dysostosis, Diamond-Blackfan anemia 2, Diamond-Blackfan anemia 15 with mandibulofacial dysostosis, Diamond-Blackfan anemia 3, Diamond-Blackfan anemia 4, Diamond-Blackfan anemia 5, Diamond-Blackfan anemia 6, Diamond-Blackfan anemia 7, Diamond-Blackfan anemia 8, Diamond-Blackfan anemia 9, Diamond-Blackfan anemia 10, Diamond-Blackfan anemia 11, Diamond-Blackfan anemia 12, Diamond-Blackfan anemia 13, Diamond-Blackfan anemia 21, Diamond-Blackfan anemia 18, Diamond-Blackfan anemia 19, Diamond-Blackfan anemia 20, Diamond-Blackfan anemia 16, Diamond-Blackfan anemia 17, Diamond-Blackfan anemia 22

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:

232 likely benign, 187 uncertain significance, 73 pathogenic, 29 benign, 27 conflicting classifications of pathogenicity, 20 likely pathogenic, 20 benign/likely benign, 12 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1460382	NC_000017.10:g.(?8136214)(8285628_?)del	ARHGEF15	Pathogenic	criteria provided, single submitter
100638	NM_000969.5(RPL5):c.244G>T (p.Glu82Ter)	DIPK1A	Pathogenic	criteria provided, single submitter
1383221	NM_000969.5(RPL5):c.608dup (p.Asn203fs)	DIPK1A	Pathogenic	criteria provided, single submitter
1451573	NM_000969.5(RPL5):c.500dup (p.Asp168fs)	DIPK1A	Pathogenic	criteria provided, single submitter
1476888	NM_000969.5(RPL5):c.527+1G>T	DIPK1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1743930	NM_000969.5(RPL5):c.48C>A (p.Tyr16Ter)	DIPK1A	Pathogenic	criteria provided, single submitter
1751601	NM_000969.5(RPL5):c.60del (p.Phe20fs)	DIPK1A	Pathogenic	criteria provided, single submitter
1752117	NM_000969.5(RPL5):c.619_620insTGTACATCGGAAGCACATCATGGGCCAGAATGTTGCAGATT (p.Tyr207fs)	DIPK1A	Pathogenic	criteria provided, single submitter
1758874	NM_000969.5(RPL5):c.742C>T (p.Arg248Ter)	DIPK1A	Pathogenic	criteria provided, single submitter
1766492	NM_000969.5(RPL5):c.92dup (p.Tyr31Ter)	DIPK1A	Pathogenic	criteria provided, single submitter
1779974	NM_000969.5(RPL5):c.178_179del (p.Ile60fs)	DIPK1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1788080	NM_000969.5(RPL5):c.222dup (p.Val75fs)	DIPK1A	Pathogenic	criteria provided, single submitter
1789249	NM_000969.5(RPL5):c.22A>T (p.Lys8Ter)	DIPK1A	Pathogenic	criteria provided, single submitter
2019799	NM_000969.5(RPL5):c.215_218del (p.Asp72fs)	DIPK1A	Pathogenic	criteria provided, single submitter
2159322	NM_000969.5(RPL5):c.479_480del (p.Phe160fs)	DIPK1A	Pathogenic	criteria provided, single submitter
10428	NM_002049.4(GATA1):c.647G>A (p.Arg216Gln)	GATA1	Pathogenic	criteria provided, multiple submitters, no conflicts
10429	NM_002049.4(GATA1):c.154_173dup (p.Ala59fs)	GATA1	Pathogenic	criteria provided, single submitter
1068556	NM_002049.4(GATA1):c.231_232dup (p.Tyr78fs)	GATA1	Pathogenic	criteria provided, multiple submitters, no conflicts
1068653	NM_002049.4(GATA1):c.3G>T (p.Met1Ile)	GATA1	Pathogenic	criteria provided, single submitter
1068951	NM_002049.4(GATA1):c.90_91del (p.Val32fs)	GATA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068952	NM_002049.4(GATA1):c.105dup (p.Ser36fs)	GATA1	Pathogenic	criteria provided, single submitter
1070439	NM_002049.4(GATA1):c.157_158insTG (p.Ala53fs)	GATA1	Pathogenic	criteria provided, single submitter
1414934	NM_002049.4(GATA1):c.192_196del (p.Arg64fs)	GATA1	Pathogenic	criteria provided, single submitter
1428144	NM_002049.4(GATA1):c.173_174insCGCTGCGC (p.Leu60fs)	GATA1	Pathogenic	criteria provided, single submitter
156265	NM_002049.4(GATA1):c.2T>C (p.Met1Thr)	GATA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
156266	NM_002049.4(GATA1):c.220G>C (p.Val74Leu)	GATA1	Pathogenic	criteria provided, single submitter
1705970	NM_002049.4(GATA1):c.220+2T>C	GATA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2031831	NM_002049.4(GATA1):c.169_170insTG (p.Ala57fs)	GATA1	Pathogenic	criteria provided, single submitter
2090004	NM_002049.4(GATA1):c.164_174dup (p.Ala59fs)	GATA1	Pathogenic	criteria provided, single submitter
2111449	NM_002049.4(GATA1):c.122_165del (p.Leu41fs)	GATA1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 109 · Orphanet: 63 · 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
RPL11	Definitive	Autosomal dominant	Diamond-Blackfan anemia 7	4
RPL5	Definitive	Autosomal dominant	Diamond-Blackfan anemia 6	4
RPS10	Definitive	Unknown	Diamond-Blackfan anemia	5
RPS19	Definitive	Autosomal dominant	Diamond-Blackfan anemia 1	6
RPS24	Definitive	Unknown	Diamond-Blackfan anemia	5
RPS26	Definitive	Autosomal dominant	Diamond-Blackfan anemia 10	4
GATA1	Strong	X-linked	thrombocytopenia, X-linked, with or without dyserythropoietic anemia	10
HEATR3	Strong	Autosomal recessive	Diamond-Blackfan anemia 21	3
RPL15	Strong	Autosomal dominant	Diamond-Blackfan anemia 12	11
RPL26	Strong	Autosomal dominant	Diamond-Blackfan anemia 11	6
RPL35A	Strong	Autosomal dominant	Diamond-Blackfan anemia 5	3
RPS17	Strong	Autosomal dominant	Diamond-Blackfan anemia 4	4
RPS29	Strong	Autosomal dominant	Diamond-Blackfan anemia 13	3
RPS7	Strong	Autosomal dominant	Diamond-Blackfan anemia 8	3
RPL18	Moderate	Autosomal dominant	Diamond-Blackfan anemia 18	4
RPL31	Moderate	Autosomal dominant	Diamond-Blackfan anemia
RPL8	Moderate	Autosomal dominant	Diamond-Blackfan anemia	2
RPL9	Moderate	Autosomal dominant	Diamond-Blackfan anemia
RPS20	Moderate	Autosomal dominant	Diamond-Blackfan anemia	6
RPS28	Moderate	Autosomal dominant	Diamond-Blackfan anemia 15 with mandibulofacial dysostosis	4
ADA2	Supportive	Autosomal dominant	Diamond-Blackfan anemia	8
RPL35	Supportive	Autosomal dominant	Diamond-Blackfan anemia	3
RPS15A	Supportive	Autosomal dominant	Diamond-Blackfan anemia	4
TSR2	Supportive	Autosomal dominant	Diamond-Blackfan anemia	4
RPS15	Limited	Autosomal dominant	Diamond-Blackfan anemia

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPL11	Orphanet:124	Diamond-Blackfan anemia
RPL26	Orphanet:124	Diamond-Blackfan anemia
RPL31	Orphanet:124	Diamond-Blackfan anemia
RPL35A	Orphanet:124	Diamond-Blackfan anemia
RPL5	Orphanet:124	Diamond-Blackfan anemia
RPL8	Orphanet:124	Diamond-Blackfan anemia
RPL9	Orphanet:124	Diamond-Blackfan anemia
RPS10	Orphanet:124	Diamond-Blackfan anemia
RPS17	Orphanet:124	Diamond-Blackfan anemia
RPS19	Orphanet:124	Diamond-Blackfan anemia
RPS20	Orphanet:124	Diamond-Blackfan anemia
RPS20	Orphanet:440437	Familial colorectal cancer Type X
RPS24	Orphanet:124	Diamond-Blackfan anemia
RPS26	Orphanet:124	Diamond-Blackfan anemia
RPS28	Orphanet:124	Diamond-Blackfan anemia
RPS7	Orphanet:124	Diamond-Blackfan anemia
HEATR3	Orphanet:124	Diamond-Blackfan anemia
GATA1	Orphanet:124	Diamond-Blackfan anemia
GATA1	Orphanet:231393	Beta-thalassemia-X-linked thrombocytopenia syndrome
GATA1	Orphanet:363727	X-linked dyserythropoietic anemia with abnormal platelets and neutropenia
GATA1	Orphanet:420611	Transient myeloproliferative syndrome
GATA1	Orphanet:67044	Thrombocytopenia with congenital dyserythropoietic anemia
GATA1	Orphanet:79277	Congenital erythropoietic porphyria
GATA1	Orphanet:86849	Acute basophilic leukemia
GATA1	Orphanet:99887	Acute megakaryoblastic leukemia in children with Down syndrome
RPL15	Orphanet:124	Diamond-Blackfan anemia
RPL18	Orphanet:124	Diamond-Blackfan anemia
RPL35	Orphanet:124	Diamond-Blackfan anemia
RPS15	Orphanet:67038	B-cell chronic lymphocytic leukemia
RPS15A	Orphanet:124	Diamond-Blackfan anemia
RPS29	Orphanet:124	Diamond-Blackfan anemia
ADA2	Orphanet:124	Diamond-Blackfan anemia
ADA2	Orphanet:404553	Deficiency of adenosine deaminase 2
ADA2	Orphanet:820	Sneddon syndrome
TSR2	Orphanet:124	Diamond-Blackfan anemia
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma

Cohort genes → proteins

40 cohort genes, 37 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	40

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPL11	HGNC:10301	ENSG00000142676	P62913	Large ribosomal subunit protein uL5	gencc,clinvar
RPL26	HGNC:10327	ENSG00000161970	P61254	Large ribosomal subunit protein uL24	gencc,clinvar
RPL31	HGNC:10334	ENSG00000071082	P62899	Large ribosomal subunit protein eL31	gencc,clinvar
RPL35A	HGNC:10345	ENSG00000182899	P18077	Large ribosomal subunit protein eL33	gencc,clinvar
RPL5	HGNC:10360	ENSG00000122406	P46777	Large ribosomal subunit protein uL18	gencc,clinvar
RPL8	HGNC:10368	ENSG00000161016	P62917	Large ribosomal subunit protein uL2	gencc,clinvar
RPL9	HGNC:10369	ENSG00000163682	P32969	Large ribosomal subunit protein uL6	gencc,clinvar
RPS10	HGNC:10383	ENSG00000124614	P46783	Small ribosomal subunit protein eS10	gencc,clinvar
RPS17	HGNC:10397	ENSG00000182774	P08708	Small ribosomal subunit protein eS17	gencc,clinvar
RPS19	HGNC:10402	ENSG00000105372	P39019	Small ribosomal subunit protein eS19	gencc,clinvar
RPS20	HGNC:10405	ENSG00000008988	P60866	Small ribosomal subunit protein uS10	gencc,clinvar
RPS24	HGNC:10411	ENSG00000138326	P62847	Small ribosomal subunit protein eS24	gencc,clinvar
RPS26	HGNC:10414	ENSG00000197728	P62854	Small ribosomal subunit protein eS26	gencc,clinvar
RPS28	HGNC:10418	ENSG00000233927	P62857	Small ribosomal subunit protein eS28	gencc,clinvar
RPS7	HGNC:10440	ENSG00000171863	P62081	Small ribosomal subunit protein eS7	gencc,clinvar
HEATR3	HGNC:26087	ENSG00000155393	Q7Z4Q2	HEAT repeat-containing protein 3	gencc,clinvar
GATA1	HGNC:4170	ENSG00000102145	P15976	Erythroid transcription factor	gencc,clinvar
RPL15	HGNC:10306	ENSG00000174748	P61313	Large ribosomal subunit protein eL15	gencc
RPL18	HGNC:10310	ENSG00000063177	Q07020	Large ribosomal subunit protein eL18	gencc
RPL35	HGNC:10344	ENSG00000136942	P42766	Large ribosomal subunit protein uL29	gencc
RPS15	HGNC:10388	ENSG00000115268	P62841	Small ribosomal subunit protein uS19	gencc
RPS15A	HGNC:10389	ENSG00000134419	P62244	Small ribosomal subunit protein uS8	gencc
RPS29	HGNC:10419	ENSG00000213741	P62273	Small ribosomal subunit protein uS14	gencc
ADA2	HGNC:1839	ENSG00000093072	Q9NZK5	Adenosine deaminase 2	gencc
TSR2	HGNC:25455	ENSG00000158526	Q969E8	Pre-rRNA-processing protein TSR2 homolog	gencc
RPL19	HGNC:10312	ENSG00000108298	P84098	Large ribosomal subunit protein eL19	clinvar
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar
ARHGEF15	HGNC:15590	ENSG00000198844	O94989	Rho guanine nucleotide exchange factor 15	clinvar
ODF4	HGNC:19056	ENSG00000184650	Q2M2E3	Outer dense fiber protein 4	clinvar
ZNF699	HGNC:24750	ENSG00000196110	Q32M78	Zinc finger protein 699	clinvar
ACTMAP	HGNC:24758	ENSG00000188493	Q5BKX5	Actin maturation protease	clinvar
DRC9	HGNC:25251	ENSG00000114473	Q9H095	Dynein regulatory complex protein 9	clinvar
GRHL3	HGNC:25839	ENSG00000158055	Q8TE85	Grainyhead-like protein 3 homolog	clinvar
DIPK1A	HGNC:32213	ENSG00000154511	Q5T7M9	Divergent protein kinase domain 1A	clinvar
FANCE	HGNC:3586	ENSG00000112039	Q9HB96	Fanconi anemia group E protein	clinvar
GFI1	HGNC:4237	ENSG00000162676	Q99684	Zinc finger protein Gfi-1	clinvar
RPL17-C18orf32	HGNC:44661	ENSG00000215472		RPL17-C18orf32 readthrough	clinvar
RPS10-NUDT3	HGNC:49181	ENSG00000270800		RPS10-NUDT3 readthrough	clinvar
MIR6797	HGNC:50169	ENSG00000276926		microRNA 6797	clinvar
PFAS	HGNC:8863	ENSG00000178921	O15067	Phosphoribosylformylglycinamidine synthase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPL11	Large ribosomal subunit protein uL5	Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.
RPL26	Large ribosomal subunit protein uL24	Component of the large ribosomal subunit.
RPL31	Large ribosomal subunit protein eL31	Component of the large ribosomal subunit.
RPL35A	Large ribosomal subunit protein eL33	Component of the large ribosomal subunit.
RPL5	Large ribosomal subunit protein uL18	Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.
RPL8	Large ribosomal subunit protein uL2	Component of the large ribosomal subunit.
RPL9	Large ribosomal subunit protein uL6	Component of the large ribosomal subunit.
RPS10	Small ribosomal subunit protein eS10	Component of the 40S ribosomal subunit.
RPS17	Small ribosomal subunit protein eS17	Component of the small ribosomal subunit.
RPS19	Small ribosomal subunit protein eS19	Component of the small ribosomal subunit.
RPS20	Small ribosomal subunit protein uS10	Component of the small ribosomal subunit.
RPS24	Small ribosomal subunit protein eS24	Component of the small ribosomal subunit.
RPS26	Small ribosomal subunit protein eS26	Component of the small ribosomal subunit.
RPS28	Small ribosomal subunit protein eS28	Component of the small ribosomal subunit.
RPS7	Small ribosomal subunit protein eS7	Component of the small ribosomal subunit.
HEATR3	HEAT repeat-containing protein 3	Plays a role in ribosome biogenesis and in nuclear import of the 60S ribosomal protein L5/large ribosomal subunit protein uL18 (RPL5).
GATA1	Erythroid transcription factor	Transcriptional activator or repressor which serves as a general switch factor for erythroid development.
RPL15	Large ribosomal subunit protein eL15	Component of the large ribosomal subunit.
RPL18	Large ribosomal subunit protein eL18	Component of the large ribosomal subunit.
RPL35	Large ribosomal subunit protein uL29	Component of the large ribosomal subunit.
RPS15	Small ribosomal subunit protein uS19	Component of the small ribosomal subunit.
RPS15A	Small ribosomal subunit protein uS8	Component of the small ribosomal subunit.
RPS29	Small ribosomal subunit protein uS14	Component of the small ribosomal subunit.
ADA2	Adenosine deaminase 2	Adenosine deaminase that may contribute to the degradation of extracellular adenosine, a signaling molecule that controls a variety of cellular responses.
TSR2	Pre-rRNA-processing protein TSR2 homolog	May be involved in 20S pre-rRNA processing.
RPL19	Large ribosomal subunit protein eL19	Component of the large ribosomal subunit.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
ARHGEF15	Rho guanine nucleotide exchange factor 15	Guanine nucleotide exchange factor (GEF) that activates RhoA, playing a role in the regulation of actin cytoskeleton organization.
ODF4	Outer dense fiber protein 4	Component of the outer dense fibers (ODF) of spermatozoa which could be involved in sperm tail structure, sperm movement and general organization of cellular cytoskeleton.
ZNF699	Zinc finger protein 699	May be involved in transcriptional regulation.
ACTMAP	Actin maturation protease	Actin maturation protease that specifically mediates the cleavage of immature acetylated N-terminal actin, thereby contributing to actin maturation.
DRC9	Dynein regulatory complex protein 9	Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes.
GRHL3	Grainyhead-like protein 3 homolog	Transcription factor playing important roles in primary neurulation and in the differentiation of stratified epithelia of both ectodermal and endodermal origin.
FANCE	Fanconi anemia group E protein	As part of the Fanconi anemia (FA) complex functions in DNA cross-links repair.
GFI1	Zinc finger protein Gfi-1	Transcription repressor essential for hematopoiesis.
PFAS	Phosphoribosylformylglycinamidine synthase	Phosphoribosylformylglycinamidine synthase involved in the purines biosynthetic pathway.

Protein-family classification

Druggable: 3 · Difficult: 7 · Unknown: 30 · Druggable fraction: 0.07

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	30	1.3×	0.049
Transcription factor	5	1.0×	0.858
Scaffold/PPI	2	0.9×	0.858
Kinase	1	0.7×	0.858
Enzyme (other)	2	0.6×	0.858

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPL11	Other/Unknown	no		Ribosomal_uL5, Ribosomal_uL5_CS, Ribosomal_uL5_dom_sf
RPL26	Scaffold/PPI	no		Ribosomal_uL24_euk_arc, KOW, Ribosomal_uL24_CS
RPL31	Other/Unknown	no		Ribosomal_eL31, Ribosomal_eL31_CS, Ribosomal_eL31_dom_sf
RPL35A	Other/Unknown	no		Ribosomal_eL33, Transl_B-barrel_sf, Ribosomal_eL33_CS
RPL5	Other/Unknown	no		Rbsml_uL18_euk_arc, Ribosomal_uL18_C_euk, Ribosomal_L18
RPL8	Scaffold/PPI	no		Ribosomal_uL2, Translation_prot_SH3-like_sf, NA-bd_OB-fold
RPL9	Other/Unknown	no		Ribosomal_uL6-like, Ribosomal_uL6_CS2, Ribosomal_uL6_a/b-dom
RPS10	Other/Unknown	no		Plectin_eS10_N, WH-like_DNA-bd_sf, Ribosomal_eS10
RPS17	Other/Unknown	no		Ribosomal_eS17, Ribosomal_eS17_CS, Ribosomal_eS17_sf
RPS19	Other/Unknown	no		Ribosomal_eS19, Ribosomal_eS19_CS, WH-like_DNA-bd_sf
RPS20	Other/Unknown	no		Ribosomal_uS10, Ribosomal_uS10_euk/arc, Ribosomal_uS10_CS
RPS24	Other/Unknown	no		Ribosomal_eS24, Ribosomal_uL23/eL15/eS24_sf, Ribosomal_eS24_CS
RPS26	Other/Unknown	no		Ribosomal_eS26, Ribosomal_eS26_sf, Ribosomal_eS26_CS
RPS28	Other/Unknown	no		Ribosomal_eS28, NA-bd_OB-fold, Ribosomal_eS28_CS
RPS7	Other/Unknown	no		Ribosomal_eS7, Ribosomal_eS7_CS
HEATR3	Other/Unknown	no		ARM-like, ARM-type_fold, SYO1-like
GATA1	Transcription factor	no		Znf_GATA, Znf_NHR/GATA, Transcription_factor_GATA
RPL15	Other/Unknown	no		Ribosomal_eL15, Ribosomal_uL23/eL15/eS24_sf, Ribosomal_eL15_CS
RPL18	Other/Unknown	no		Ribosomal_eL18, Ribosomal_uL15/eL18, Ribosomal_eL18/eL18-A/B/_CS
RPL35	Other/Unknown	no		Ribosomal_uL29, Ribosomal_uL29_CS, Ribosomal_uL29_sf
RPS15	Other/Unknown	no		Ribosomal_uS19, Ribosomal_uS19_euk_arc, Ribosomal_uS19_CS
RPS15A	Other/Unknown	no		Ribosomal_uS8, Ribosomal_uS8_sf, Ribosomal_uS8_CS
RPS29	Other/Unknown	no		Ribosomal_uS14, Ribosomal_uS14_CS, RIbosomal_uS14_euk_arc
ADA2	Enzyme (other)	yes	3.5.4.4	A_deaminase_dom, Ado/ade_deaminase, ADGF
TSR2	Other/Unknown	no		Pre-rRNA_process_TSR2
RPL19	Other/Unknown	no		Ribosomal_eL19_dom, Ribosomal_eL19_dom1, Ribosomal_eL19_CS
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
ARHGEF15	Other/Unknown	no		DH_dom, PH-like_dom_sf, DBL_dom_sf
ODF4	Other/Unknown	no
ZNF699	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
ACTMAP	Other/Unknown	no		ACTMAP
DRC9	Other/Unknown	no		IQ_motif_EF-hand-BS, IQCG
GRHL3	Transcription factor	no		CP2, TF_CP2-like, GRHL1/CP2_C
DIPK1A	Kinase	yes		FAM69_kinase_dom, FAM69_N
FANCE	Other/Unknown	no		Fanconi_anaemia_gr_E_prot_C, FANCE
GFI1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
RPL17-C18orf32	Other/Unknown	no
RPS10-NUDT3	Other/Unknown	no
MIR6797	Other/Unknown	no
PFAS	Enzyme (other)	yes	6.3.5.3	PurL_large, PurM-like_C_dom, Class_I_gatase-like

Expression context

Cohort genes with no expression data: 0.

36 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)	40
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ganglionic eminence	8
left ovary	8
cortical plate	7
primordial germ cell in gonad	7
calcaneal tendon	4
monocyte	3
skin of hip	3
tendon of biceps brachii	3
right ovary	3
granulocyte	3
lower esophagus mucosa	3
caput epididymis	2
upper leg skin	2
parietal pleura	2
ovary	2
right uterine tube	2
adult organism	2
mucosa of transverse colon	2
adenohypophysis	2
leukocyte	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPL11	293	ubiquitous	marker	ganglionic eminence, cortical plate, monocyte
RPL26	134	ubiquitous	marker	cortical plate, calcaneal tendon, ganglionic eminence
RPL31	288	ubiquitous	marker	skin of hip, upper leg skin, caput epididymis
RPL35A	288	ubiquitous	marker	tendon of biceps brachii, left ovary, skin of hip
RPL5	292	ubiquitous	marker	germinal epithelium of ovary, primordial germ cell in gonad, parietal pleura
RPL8	153	ubiquitous	marker	endometrium epithelium, primordial germ cell in gonad, ovary
RPL9	158	ubiquitous	marker	cortical plate, left ovary, right ovary
RPS10	134	ubiquitous	marker	primordial germ cell in gonad, left ovary, right ovary
RPS17	134	ubiquitous	marker	ganglionic eminence, corpus callosum, left ovary
RPS19	301	ubiquitous	marker	upper leg skin, right uterine tube, skin of hip
RPS20	311	ubiquitous	marker	adult organism, left ovary, lymph node
RPS24	288	ubiquitous	marker	ganglionic eminence, mucosa of sigmoid colon, colonic mucosa
RPS26	140	ubiquitous	marker	granulocyte, left adrenal gland cortex, mucosa of transverse colon
RPS28	250	ubiquitous	marker	lower esophagus mucosa, adenohypophysis, mucosa of transverse colon
RPS7	134	ubiquitous	marker	primordial germ cell in gonad, ovary, left ovary
HEATR3	248	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
GATA1	138	tissue_specific	marker	trabecular bone tissue, blood, bone marrow
RPL15	303	ubiquitous	marker	left ovary, cortical plate, right ovary
RPL18	304	ubiquitous	marker	nipple, penis, adult organism
RPL35	295	ubiquitous	marker	skin of abdomen, skin of leg, lower esophagus mucosa
RPS15	149	ubiquitous	marker	pituitary gland, adenohypophysis, right hemisphere of cerebellum
RPS15A	233	ubiquitous	marker	calcaneal tendon, ganglionic eminence, left ovary
RPS29	295	ubiquitous	marker	caput epididymis, penis, parietal pleura
ADA2	254	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
TSR2	289	ubiquitous	marker	tendon of biceps brachii, medial globus pallidus, globus pallidus
RPL19	301	ubiquitous	marker	primordial germ cell in gonad, calcaneal tendon, granulocyte
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
ARHGEF15	198	broad	marker	apex of heart, omental fat pad, peritoneum
ODF4	41	tissue_specific	yes	left testis, sperm, right testis
ZNF699	134	broad	yes	calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis, cortical plate

Protein interactions among cohort

Intra-cohort edges: 77.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
RPL5	6,028
RPL9	5,784
RPS19	5,129
RPL35	4,841
GATA1	4,810
RPL18	4,722
RPL26	4,651
RPS10	4,418
RPL35A	3,614

Intra-cohort edges

A	B	Sources
DIPK1A	RPL5	string_interaction
GATA1	GFI1	string_interaction
GFI1	TP53	intact
HEATR3	RPL5	string_interaction
HEATR3	TSR2	string_interaction
RPL11	RPL15	biogrid_interaction
RPL11	RPL19	biogrid_interaction
RPL11	RPL35	biogrid_interaction
RPL11	RPL5	biogrid_interaction
RPL11	RPS10	biogrid_interaction
RPL11	RPS15	biogrid_interaction
RPL11	RPS15A	biogrid_interaction
RPL11	RPS20	biogrid_interaction
RPL15	RPL18	biogrid_interaction
RPL15	RPL19	biogrid_interaction
RPL15	RPL26	biogrid_interaction
RPL15	RPL31	biogrid_interaction
RPL15	RPL35	biogrid_interaction
RPL15	RPL35A	biogrid_interaction
RPL15	RPL5	biogrid_interaction
RPL15	RPL8	biogrid_interaction
RPL15	RPS10	biogrid_interaction
RPL15	RPS15	biogrid_interaction
RPL15	RPS15A	biogrid_interaction
RPL15	RPS20	biogrid_interaction
RPL15	RPS26	biogrid_interaction
RPL18	RPL5	string_interaction
RPL18	RPL8	biogrid_interaction, intact
RPL18	RPS10	string_interaction
RPL18	RPS15A	biogrid_interaction
RPL18	RPS19	biogrid_interaction, string_interaction
RPL18	RPS20	biogrid_interaction
RPL18	TSR2	string_interaction
RPL19	RPL26	biogrid_interaction
RPL19	RPS19	biogrid_interaction
RPL19	RPS20	biogrid_interaction
RPL19	RPS29	biogrid_interaction
RPL26	RPL35	string_interaction
RPL26	RPL35A	string_interaction
RPL26	RPL5	string_interaction
RPL26	RPS19	string_interaction
RPL26	TP53	string_interaction
RPL31	RPS15	biogrid_interaction
RPL31	RPS19	biogrid_interaction
RPL31	RPS20	biogrid_interaction
RPL35	RPL5	string_interaction
RPL35	RPS10	biogrid_interaction
RPL35	RPS19	biogrid_interaction
RPL35	RPS20	biogrid_interaction
RPL35A	RPL5	string_interaction

Structural data

PDB: 28 · AlphaFold-only: 9 · No structure: 3

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313
RPS24	P62847	214
RPS28	P62857	214
RPS15A	P62244	213
RPS17	P08708	212
RPS7	P62081	212
RPS19	P39019	210
RPS15	P62841	208
RPS10	P46783	200
RPS29	P62273	200
RPS20	P60866	199
RPL35	P42766	199
RPL26	P61254	197
RPL18	Q07020	196
RPL35A	P18077	194
RPL9	P32969	193
RPL15	P61313	192
RPS26	P62854	190
RPL19	P84098	190
RPL31	P62899	186
RPL11	P62913	185
RPL5	P46777	184
RPL8	P62917	181
FANCE	Q9HB96	7
DRC9	Q9H095	3
PFAS	O15067	3
ADA2	Q9NZK5	2
GATA1	P15976	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ACTMAP	Q5BKX5	83.63
DIPK1A	Q5T7M9	83.20
HEATR3	Q7Z4Q2	83.07
TSR2	Q969E8	74.60
ZNF699	Q32M78	70.23
ARHGEF15	O94989	62.96
GRHL3	Q8TE85	61.27
GFI1	Q99684	58.33
ODF4	Q2M2E3	55.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 124. Enrichment computed across 40 evidence-associated genes (30 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 30 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Peptide chain elongation	22	93.0×	1e-39	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10 (+14 more)
Viral mRNA Translation	22	93.0×	1e-39	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10 (+14 more)
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	22	92.0×	1e-39	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10 (+14 more)
Selenocysteine synthesis	22	88.2×	2e-39	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10 (+14 more)
Eukaryotic Translation Termination	22	88.2×	2e-39	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10 (+14 more)
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	22	86.3×	2e-39	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10 (+14 more)
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	22	86.3×	2e-39	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10 (+14 more)
Formation of a pool of free 40S subunits	22	82.1×	6e-39	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10 (+14 more)
Response of EIF2AK4 (GCN2) to amino acid deficiency	22	81.3×	7e-39	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10 (+14 more)
L13a-mediated translational silencing of Ceruloplasmin expression	22	74.1×	6e-38	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10 (+14 more)
SRP-dependent cotranslational protein targeting to membrane	22	73.5×	6e-38	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10 (+14 more)
GTP hydrolysis and joining of the 60S ribosomal subunit	22	73.5×	6e-38	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10 (+14 more)
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	22	71.6×	1e-37	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10 (+14 more)
Regulation of expression of SLITs and ROBOs	22	50.8×	4e-34	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10 (+14 more)
Major pathway of rRNA processing in the nucleolus and cytosol	22	45.3×	5e-33	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10 (+14 more)
Eukaryotic Translation Initiation	11	113.2×	3e-20	RPS10, RPS17, RPS19, RPS20, RPS24, RPS26, RPS28, RPS7 (+3 more)
Cap-dependent Translation Initiation	11	113.2×	3e-20	RPS10, RPS17, RPS19, RPS20, RPS24, RPS26, RPS28, RPS7 (+3 more)
SARS-CoV-1 modulates host translation machinery	11	113.2×	3e-20	RPS10, RPS17, RPS19, RPS20, RPS24, RPS26, RPS28, RPS7 (+3 more)
Eukaryotic Translation Elongation	11	102.1×	1e-19	RPS10, RPS17, RPS19, RPS20, RPS24, RPS26, RPS28, RPS7 (+3 more)
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	11	99.7×	1e-19	RPS10, RPS17, RPS19, RPS20, RPS24, RPS26, RPS28, RPS7 (+3 more)
Nonsense-Mediated Decay (NMD)	11	85.5×	8e-19	RPS10, RPS17, RPS19, RPS20, RPS24, RPS26, RPS28, RPS7 (+3 more)
SARS-CoV-2 modulates host translation machinery	11	82.1×	1e-18	RPS10, RPS17, RPS19, RPS20, RPS24, RPS26, RPS28, RPS7 (+3 more)
Influenza Viral RNA Transcription and Replication	11	79.0×	2e-18	RPS10, RPS17, RPS19, RPS20, RPS24, RPS26, RPS28, RPS7 (+3 more)
Formation of the ternary complex, and subsequently, the 43S complex	11	79.0×	2e-18	RPS10, RPS17, RPS19, RPS20, RPS24, RPS26, RPS28, RPS7 (+3 more)
Selenoamino acid metabolism	11	72.2×	5e-18	RPS10, RPS17, RPS19, RPS20, RPS24, RPS26, RPS28, RPS7 (+3 more)
Translation initiation complex formation	11	69.8×	7e-18	RPS10, RPS17, RPS19, RPS20, RPS24, RPS26, RPS28, RPS7 (+3 more)
Ribosomal scanning and start codon recognition	11	69.8×	7e-18	RPS10, RPS17, RPS19, RPS20, RPS24, RPS26, RPS28, RPS7 (+3 more)
Influenza Infection	11	64.4×	2e-17	RPS10, RPS17, RPS19, RPS20, RPS24, RPS26, RPS28, RPS7 (+3 more)
SARS-CoV-1-host interactions	11	64.4×	2e-17	RPS10, RPS17, RPS19, RPS20, RPS24, RPS26, RPS28, RPS7 (+3 more)
Cellular response to starvation	11	60.7×	4e-17	RPS10, RPS17, RPS19, RPS20, RPS24, RPS26, RPS28, RPS7 (+3 more)

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 36 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cytoplasmic translation	22	113.2×	7e-40	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10 (+14 more)
translation	22	62.8×	5e-34	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10 (+14 more)
rRNA processing	10	39.3×	4e-12	RPL11, RPL26, RPL35A, RPL5, RPS17, RPS19, RPS24, RPS28 (+2 more)
ribosomal small subunit biogenesis	7	44.3×	1e-08	RPS17, RPS19, RPS24, RPS28, RPS7, RPS15, RPS15A
ribosomal large subunit biogenesis	5	61.6×	7e-07	RPL11, RPL26, RPL35A, RPL5, HEATR3
ribosomal small subunit assembly	3	117.0×	8e-05	RPS19, RPS28, RPS15
positive regulation of signal transduction by p53 class mediator	3	100.3×	1e-04	RPL11, RPS20, RPS15
negative regulation of ubiquitin-dependent protein catabolic process	3	70.2×	3e-04	RPL11, RPL5, RPS7
ribosomal large subunit assembly	2	78.0×	0.008	RPL11, RPL5
erythrocyte homeostasis	2	72.0×	0.008	RPS17, RPS24
maturation of SSU-rRNA	2	42.6×	0.021	RPS19, RPS28
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	2	37.5×	0.025	RPS19, TSR2
negative regulation of helicase activity	1	468.1×	0.028	TP53
cellular response to actinomycin D	1	468.1×	0.028	TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	468.1×	0.028	TP53
negative regulation of G1 to G0 transition	1	468.1×	0.028	TP53
regulation of translation involved in cellular response to UV	1	468.1×	0.028	RPL26
cellular response to gamma radiation	2	33.4×	0.028	RPL26, TP53
regulation of primitive erythrocyte differentiation	1	234.1×	0.036	GATA1
basophil differentiation	1	234.1×	0.036	GATA1
positive regulation of mitochondrial membrane permeability	1	234.1×	0.036	TP53
eosinophil fate commitment	1	234.1×	0.036	GATA1
positive regulation of respiratory burst involved in inflammatory response	1	234.1×	0.036	RPS19
oligodendrocyte apoptotic process	1	234.1×	0.036	TP53
positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1	234.1×	0.036	RPL26
negative regulation of glucose catabolic process to lactate via pyruvate	1	234.1×	0.036	TP53
negative regulation of pentose-phosphate shunt	1	234.1×	0.036	TP53
regulation of signal transduction by p53 class mediator	2	21.3×	0.036	RPL11, RPL5
DNA damage response, signal transduction by p53 class mediator	2	19.9×	0.037	RPL26, TP53
purine ribonucleoside monophosphate biosynthetic process	1	156.0×	0.039	PFAS

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

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

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Daclizumab, Filgrastim, Fludarabine Phosphate, Melphalan, Methotrexate, Mycophenolate Mofetil, Tacrolimus Anhydrous.

Drug target analysis

Approved (phase 4): 23 · Phase ≥3: 23 · Phased (≥1): 23 · Undrugged: 17

Druggability breadth: 25 of 40 evidence-associated genes (62%) 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
RPL11	GENTAMICIN SULFATE
RPL26	GENTAMICIN SULFATE
RPL31	GENTAMICIN SULFATE
RPL35A	GENTAMICIN SULFATE
RPL5	GENTAMICIN SULFATE
RPL8	GENTAMICIN SULFATE
RPL9	GENTAMICIN SULFATE
RPS10	GENTAMICIN SULFATE
RPS17	GENTAMICIN SULFATE
RPS19	GENTAMICIN SULFATE
RPS20	GENTAMICIN SULFATE
RPS24	GENTAMICIN SULFATE
RPS26	GENTAMICIN SULFATE
RPS28	GENTAMICIN SULFATE
RPS7	GENTAMICIN SULFATE
RPL15	GENTAMICIN SULFATE
RPL18	GENTAMICIN SULFATE
RPL35	GENTAMICIN SULFATE
RPS15	GENTAMICIN SULFATE
RPS15A	GENTAMICIN SULFATE
RPS29	GENTAMICIN SULFATE
RPL19	GENTAMICIN SULFATE
TP53	NITROFURANTOIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
RPS10	2	4
RPS19	2	4
RPS15A	2	4
RPS29	2	4
RPL11	1	4
RPL26	1	4
RPL31	1	4
RPL35A	1	4
RPL5	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPL11, RPL15, RPL18, RPL19, RPL26, RPL31
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
RPS10	97	Binding:97
RPS19	97	Binding:97
RPS7	96	Binding:96
RPS15A	96	Binding:96
RPS29	96	Binding:96
RPL11	90	Binding:90
RPL26	90	Binding:90
RPL31	90	Binding:90
RPL35A	90	Binding:90
RPL5	90	Binding:90
RPL8	90	Binding:90
RPL9	90	Binding:90
RPS17	90	Binding:90
RPS20	90	Binding:90
RPS24	90	Binding:90
RPS28	90	Binding:90
RPL15	90	Binding:90
RPL18	90	Binding:90
RPL35	90	Binding:90
RPS15	90	Binding:90
RPL19	90	Binding:90
RPS26	89	Binding:89
GFI1	6	Binding:6
PFAS	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ADA2	3.5.4.4	adenosine deaminase
PFAS	6.3.5.3	phosphoribosylformylglycinamidine synthase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TP53	869

Pharmacogenomics

Cohort genes with a PharmGKB record: 37; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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	RPL11, RPL15, RPL18, RPL19, RPL26, RPL31
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	23	RPL11, RPL26, RPL31, RPL35A, RPL5, RPL8, RPL9, RPS10, RPS17, RPS19 (+13 more)
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	ADA2, PFAS
D	Druggable family + AlphaFold only, no drug	1	DIPK1A
E	Difficult family or no structure, no drug	14	HEATR3, GATA1, TSR2, ARHGEF15, ODF4, ZNF699, ACTMAP, DRC9, GRHL3, FANCE (+4 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
HEATR3	0	RPL5
TSR2	0	RPL5
GATA1	0	—
ADA2	0	—
ARHGEF15	0	—
ODF4	0	—
ZNF699	0	—
ACTMAP	0	—
DRC9	0	—
GRHL3	0	—
DIPK1A	0	—
FANCE	0	—
GFI1	6	—
RPL17-C18orf32	0	—
RPS10-NUDT3	0	—
MIR6797	0	—
PFAS	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 38.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	12
PHASE2	10
PHASE1/PHASE2	10
PHASE2/PHASE3	2
PHASE1	2
PHASE4	1
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00673608	PHASE4	COMPLETED	Magnetic Resonance Imaging (MRI) Assessments of the Heart and Liver Iron Load in Patients With Transfusion Induced Iron Overload
NCT00176852	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant for Hemoglobinopathy
NCT00176878	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant for Bone Marrow Failure Syndromes
NCT00235391	PHASE3	COMPLETED	Expanded Access of Deferasirox to Patients With Congenital Disorders of Red Blood Cells and Chronic Iron Overload
NCT01966367	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation
NCT03653338	PHASE1/PHASE2	RECRUITING	T-Cell Depleted Alternative Donor Bone Marrow Transplant for Sickle Cell Disease (SCD) and Other Anemias
NCT04099966	PHASE2	RECRUITING	AlloSCT for Malignant and Non-malignant Hematologic Diseases Utilizing Alpha/Beta T Cell and CD19+ B Cell Depletion
NCT00001962	PHASE2	TERMINATED	A Study to Determine Whether Therapy With Daclizumab Will Benefit Patients With Bone Marrow Failure
NCT00011505	PHASE2	COMPLETED	Mobilization of Stem Cells With G-CSF for Collection From Patients With Diamond-Blackfan Anemia
NCT00301834	PHASE2	COMPLETED	Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders
NCT00305708	PHASE1/PHASE2	COMPLETED	Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remission
NCT00957931	PHASE2	COMPLETED	Allo-HCT MUD for Non-malignant Red Blood Cell (RBC) Disorders: Sickle Cell, Thal, and DBA: Reduced Intensity Conditioning, Co-tx MSCs
NCT01362595	PHASE1/PHASE2	COMPLETED	Pilot Phase I/II Study of Amino Acid Leucine in Treatment of Patients With Transfusion-Dependent Diamond Blackfan Anemia
NCT01419704	PHASE1/PHASE2	WITHDRAWN	Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies
NCT01464164	PHASE1/PHASE2	TERMINATED	Safety and Efficacy Study of Sotatercept in Adults With Transfusion Dependent Diamond Blackfan Anemia
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT02065869	PHASE1/PHASE2	TERMINATED	Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant
NCT02386267	PHASE2	UNKNOWN	L-leucine in Diamond Blackfan Anemia Patients
NCT02512679	PHASE2	TERMINATED	Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells
NCT03333486	PHASE2	TERMINATED	Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT03733249	PHASE1/PHASE2	TERMINATED	Long Term Follow-up Study for Patients Enrolled on the BP-004 Clinical Study
NCT03966053	PHASE1/PHASE2	TERMINATED	The Use of Trifluoperazine in Transfusion Dependent DBA
NCT04965597	PHASE2	COMPLETED	Treosulfan-Based Conditioning Regimen Before a Blood or Bone Marrow Transplant for the Treatment of Bone Marrow Failure Diseases (BMT CTN 1904)
NCT01586455	PHASE1	COMPLETED	Human Placental-Derived Stem Cell Transplantation
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT00027274	Not specified	RECRUITING	Cancer in Inherited Bone Marrow Failure Syndromes
NCT02720679	Not specified	RECRUITING	Investigation of the Genetics of Hematologic Diseases
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT07186179	Not specified	RECRUITING	Mobilization of CD34+ Peripheral Blood Stem Cells in Patients With Diamond Blackfan Anemia Syndrome (DBAS)
NCT00244010	Not specified	COMPLETED	Partially Matched Stem Cell Transplantation for Patients With Refractory Severe Aplastic Anemia or Refractory Cytopenias
NCT00290628	Not specified	TERMINATED	Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer
NCT01114776	Not specified	COMPLETED	Multi-Center Study of Iron Overload: Pilot Study
NCT01319851	Not specified	TERMINATED	Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
NCT01758042	Not specified	COMPLETED	Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders
NCT01913548	Not specified	COMPLETED	Multi-Center Study of Iron Overload: Survey Study (MCSIO)
NCT02179359	Not specified	TERMINATED	Hematopoietic Stem Cell Transplant for High Risk Hemoglobinopathies
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLUDARABINE PHOSPHATE	4	8
BUSULFAN	4	2
DEFERASIROX	4	2
ALEFACEPT	4	1
ALEMTUZUMAB	4	1
DACLIZUMAB	4	1
SOTATERCEPT	4	1
TREOSULFAN	4	1
TRIFLUOPERAZINE	4	1
LEUCINE	3	2
FLUDARABINE	3	1
RIMIDUCID	2	2
RIVOGENLECLEUCEL	2	1
CHEMBL290077	0	1