Diamond-Blackfan anemia 12

disease

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Also known as DBA12Diamond-Blackfan anaemia caused by mutation in RPL15Diamond-Blackfan Anaemia type 12Diamond-Blackfan anemia caused by mutation in RPL15Diamond-Blackfan Anemia type 12RPL15 Diamond-Blackfan anaemiaRPL15 Diamond-Blackfan anemia

Summary

Diamond-Blackfan anemia 12 (MONDO:0014245) is a disease caused by RPL15 (GenCC Strong), with 2 cohort genes.

At a glance

Causal gene: RPL15 (GenCC Strong)
Cohort genes: 2
ClinVar variants: 21

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Diamond-Blackfan anemia 12
Mondo ID	MONDO:0014245
OMIM	615550
DOID	DOID:0111882
UMLS	C3809888
MedGen	816218
GARD	0015985
Is cancer (heuristic)	no

Also known as: DBA12 · Diamond-Blackfan anaemia caused by mutation in RPL15 · Diamond-Blackfan Anaemia type 12 · Diamond-Blackfan anemia 12 · Diamond-Blackfan anemia caused by mutation in RPL15 · Diamond-Blackfan Anemia type 12 · RPL15 Diamond-Blackfan anaemia · RPL15 Diamond-Blackfan anemia

Data availability: 21 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › pure red-cell aplasia › Diamond-Blackfan anemia › Diamond-Blackfan anemia 12

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

21 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 6 pathogenic, 4 benign, 1 benign/likely benign, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1709989	NM_002948.5(RPL15):c.130del (p.Arg44fs)	NKIRAS1	Pathogenic	criteria provided, single submitter
2502335	NM_002948.5(RPL15):c.242dup (p.Tyr81Ter)	NKIRAS1	Pathogenic	criteria provided, single submitter
2502336	NM_002948.5(RPL15):c.85C>T (p.Gln29Ter)	NKIRAS1	Pathogenic	no assertion criteria provided
2502337	NM_002948.5(RPL15):c.29T>C (p.Leu10Pro)	NKIRAS1	Pathogenic	no assertion criteria provided
2502338	NM_002948.5(RPL15):c.458A>C (p.Lys153Thr)	NKIRAS1	Pathogenic	no assertion criteria provided
88980	NM_001253384.2(RPL15):c.309+91_361-539del	NKIRAS1	Pathogenic	no assertion criteria provided
870411	NM_002948.5(RPL15):c.314G>T (p.Arg105Leu)	NKIRAS1	Likely pathogenic	criteria provided, single submitter
626158	NM_002948.5(RPL15):c.172+5G>A	NKIRAS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030605	NM_002948.5(RPL15):c.536A>G (p.Lys179Arg)	NKIRAS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1337815	NM_002948.5(RPL15):c.563G>A (p.Arg188His)	NKIRAS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1391914	NM_002948.5(RPL15):c.458A>G (p.Lys153Arg)	NKIRAS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3377047	NM_002948.5(RPL15):c.553G>A (p.Gly185Ser)	NKIRAS1	Uncertain significance	criteria provided, single submitter
3589121	NM_002948.5(RPL15):c.231G>A (p.Lys77=)	NKIRAS1	Uncertain significance	criteria provided, single submitter
3589122	NM_002948.5(RPL15):c.584G>A (p.Arg195His)	NKIRAS1	Uncertain significance	criteria provided, single submitter
3906961	NM_002948.5(RPL15):c.227del (p.Pro76fs)	NKIRAS1	Uncertain significance	criteria provided, single submitter
4277955	NM_001253384.2(RPL15):c.375_376del (p.His126fs)	NKIRAS1	Uncertain significance	criteria provided, single submitter
1259048	NC_000003.12:g.23921643C>T	NKIRAS1	Benign	criteria provided, multiple submitters, no conflicts
1639733	NM_002948.5(RPL15):c.173-18G>A	NKIRAS1	Benign	criteria provided, multiple submitters, no conflicts
436551	NM_002948.5(RPL15):c.75C>G (p.Val25=)	NKIRAS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
516587	NM_002948.5(RPL15):c.309+13G>C	NKIRAS1	Benign	criteria provided, multiple submitters, no conflicts
788484	NM_002948.5(RPL15):c.243C>T (p.Tyr81=)	NKIRAS1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 1 · 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
RPL15	Strong	Autosomal dominant	Diamond-Blackfan anemia 12	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPL15	Orphanet:124	Diamond-Blackfan anemia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPL15	HGNC:10306	ENSG00000174748	P61313	Large ribosomal subunit protein eL15	gencc
NKIRAS1	HGNC:17899	ENSG00000197885	Q9NYS0	NF-kappa-B inhibitor-interacting Ras-like protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPL15	Large ribosomal subunit protein eL15	Component of the large ribosomal subunit.
NKIRAS1	NF-kappa-B inhibitor-interacting Ras-like protein 1	Atypical Ras-like protein that acts as a potent regulator of NF-kappa-B activity by preventing the degradation of NF-kappa-B inhibitor beta (NFKBIB) by most signals, explaining why NFKBIB is more resistant to degradation.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPL15	Other/Unknown	no		Ribosomal_eL15, Ribosomal_uL23/eL15/eS24_sf, Ribosomal_eL15_CS
NKIRAS1	Other/Unknown	no		Small_GTPase, Small_GTP-bd, P-loop_NTPase

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
left ovary	1
right ovary	1
lateral nuclear group of thalamus	1
pons	1
substantia nigra pars compacta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPL15	303	ubiquitous	marker	left ovary, cortical plate, right ovary
NKIRAS1	251	ubiquitous	marker	lateral nuclear group of thalamus, pons, substantia nigra pars compacta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPL15	1,011
NKIRAS1	466

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPL15	P61313	192
NKIRAS1	Q9NYS0	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 44. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
ZBP1(DAI) mediated induction of type I IFNs	1	519.1×	0.024	NKIRAS1
RIP-mediated NFkB activation via ZBP1	1	335.9×	0.024	NKIRAS1
TRAF6 mediated NF-kB activation	1	228.4×	0.024	NKIRAS1
TAK1-dependent IKK and NF-kappa-B activation	1	150.3×	0.024	NKIRAS1
Cytosolic sensors of pathogen-associated DNA	1	142.8×	0.024	NKIRAS1
Interleukin-1 family signaling	1	135.9×	0.024	NKIRAS1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1	126.9×	0.024	NKIRAS1
Toll Like Receptor 10 (TLR10) Cascade	1	107.7×	0.024	NKIRAS1
Toll Like Receptor 5 (TLR5) Cascade	1	107.7×	0.024	NKIRAS1
MyD88 cascade initiated on plasma membrane	1	102.0×	0.024	NKIRAS1
Toll Like Receptor 3 (TLR3) Cascade	1	96.8×	0.024	NKIRAS1
TRIF (TICAM1)-mediated TLR4 signaling	1	95.2×	0.024	NKIRAS1
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1	95.2×	0.024	NKIRAS1
MyD88 dependent cascade initiated on endosome	1	95.2×	0.024	NKIRAS1
MyD88-independent TLR4 cascade	1	92.1×	0.024	NKIRAS1
Toll Like Receptor 7/8 (TLR7/8) Cascade	1	92.1×	0.024	NKIRAS1
Toll Like Receptor 9 (TLR9) Cascade	1	87.8×	0.024	NKIRAS1
Toll Like Receptor TLR6:TLR2 Cascade	1	87.8×	0.024	NKIRAS1
Toll Like Receptor 2 (TLR2) Cascade	1	86.5×	0.024	NKIRAS1
Toll Like Receptor TLR1:TLR2 Cascade	1	84.0×	0.024	NKIRAS1
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1	76.1×	0.024	NKIRAS1
Toll Like Receptor 4 (TLR4) Cascade	1	65.6×	0.024	NKIRAS1
Peptide chain elongation	1	63.4×	0.024	RPL15
Viral mRNA Translation	1	63.4×	0.024	RPL15
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	1	62.8×	0.024	RPL15
Toll-like Receptor Cascades	1	62.1×	0.024	NKIRAS1
Interleukin-1 signaling	1	62.1×	0.024	NKIRAS1
Selenocysteine synthesis	1	60.1×	0.024	RPL15
Eukaryotic Translation Termination	1	60.1×	0.024	RPL15
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	1	58.9×	0.024	RPL15

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
Ral protein signal transduction	1	2106.5×	0.003	NKIRAS1
surfactant homeostasis	1	401.2×	0.007	NKIRAS1
regulation of tumor necrosis factor-mediated signaling pathway	1	351.1×	0.007	NKIRAS1
lung alveolus development	1	175.5×	0.010	NKIRAS1
cytoplasmic translation	1	92.6×	0.014	RPL15
negative regulation of canonical NF-kappaB signal transduction	1	86.0×	0.014	NKIRAS1
translation	1	51.4×	0.019	RPL15

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 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
RPL15	GENTAMICIN SULFATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RPL15	1	4
NKIRAS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPL15

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RPL15	90	Binding:90

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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	RPL15

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RPL15
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	1	NKIRAS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NKIRAS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: RPL15, NKIRAS1