Diamond-Blackfan anemia 8

Summary

Diamond-Blackfan anemia 8 (MONDO:0012939) is a disease caused by RPS7 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: RPS7 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 192

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Diamond-Blackfan anemia 8
Mondo ID	MONDO:0012939
MeSH	C567253
OMIM	612563
DOID	DOID:0111881
NCIT	C176917
UMLS	C2675511
MedGen	390817
GARD	0015570
Is cancer (heuristic)	no

Also known as: DBA8 · Diamond-Blackfan anaemia caused by mutation in RPS7 · Diamond-Blackfan Anaemia type 8 · Diamond-Blackfan anemia 8 · Diamond-Blackfan anemia caused by mutation in RPS7 · Diamond-Blackfan Anemia type 8 · RPS7 Diamond-Blackfan anaemia · RPS7 Diamond-Blackfan anemia

Data availability: 192 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 8

Related subtypes (21): 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 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

192 retrieved; paginated sample, class counts are floors:

88 uncertain significance, 73 likely benign, 8 benign, 8 conflicting classifications of pathogenicity, 6 likely pathogenic, 5 pathogenic, 4 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1031721	NM_001011.4(RPS7):c.75+1G>A	RPS7	Pathogenic	criteria provided, multiple submitters, no conflicts
2697321	NM_001011.4(RPS7):c.-19+1G>T	RPS7	Pathogenic	criteria provided, single submitter
2761151	NM_001011.4(RPS7):c.-19+2T>A	RPS7	Pathogenic	criteria provided, single submitter
372193	NM_001011.4(RPS7):c.76-1G>T	RPS7	Pathogenic	no assertion criteria provided
6150	NM_001011.4(RPS7):c.147+1G>A	RPS7	Pathogenic	no assertion criteria provided
2500885	NM_001011.4(RPS7):c.65_68del (p.Gly22fs)	RPS7	Likely pathogenic	criteria provided, single submitter
2780000	NM_001011.4(RPS7):c.75+1G>T	RPS7	Likely pathogenic	criteria provided, single submitter
3654517	NM_001011.4(RPS7):c.399G>C (p.Leu133Phe)	RPS7	Likely pathogenic	criteria provided, single submitter
4763762	NM_001011.4(RPS7):c.75+2T>G	RPS7	Likely pathogenic	criteria provided, single submitter
692152	NM_001011.4(RPS7):c.508-3T>G	RPS7	Likely pathogenic	no assertion criteria provided
975849	NM_001011.4(RPS7):c.-19+1G>A	RPS7	Likely pathogenic	criteria provided, single submitter
1336656	NM_001011.4(RPS7):c.525T>G (p.Gly175=)	RPS7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1337630	NM_001011.4(RPS7):c.148-6C>T	RPS7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1490897	NM_001011.4(RPS7):c.66C>T (p.Gly22=)	RPS7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2038414	NM_001011.4(RPS7):c.79C>A (p.Leu27Ile)	RPS7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
335902	NM_001011.4(RPS7):c.39C>T (p.Gly13=)	RPS7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3586577	NM_001011.4(RPS7):c.402C>T (p.Val134=)	RPS7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
424204	NM_001011.4(RPS7):c.-19+1G>C	RPS7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
469408	NM_001011.4(RPS7):c.357-3dup	RPS7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1373870	NC_000002.11:g.(?3391395)(3691708_?)dup	ADI1	Uncertain significance	criteria provided, single submitter
2423465	NC_000002.11:g.(?3391395)(3624240_?)dup	ADI1	Uncertain significance	criteria provided, single submitter
1014731	NC_000002.11:g.(?3622941)(3628472_?)dup	RPS7	Uncertain significance	criteria provided, single submitter
1024764	NM_001011.4(RPS7):c.356+3G>A	RPS7	Uncertain significance	criteria provided, single submitter
1028444	NM_001011.4(RPS7):c.-3G>A	RPS7	Uncertain significance	criteria provided, single submitter
1037436	NM_001011.4(RPS7):c.113C>T (p.Ala38Val)	RPS7	Uncertain significance	criteria provided, single submitter
1040145	NM_001011.4(RPS7):c.157G>A (p.Val53Ile)	RPS7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1050877	NM_001011.4(RPS7):c.520T>G (p.Ser174Ala)	RPS7	Uncertain significance	criteria provided, single submitter
1064152	NM_001011.4(RPS7):c.357-3del	RPS7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1308885	NM_001011.4(RPS7):c.291+2dup	RPS7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1357068	NM_001011.4(RPS7):c.436G>A (p.Val146Ile)	RPS7	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
RPS7	Strong	Autosomal dominant	Diamond-Blackfan anemia 8	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPS7	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
RPS7	HGNC:10440	ENSG00000171863	P62081	Small ribosomal subunit protein eS7	gencc,clinvar
ADI1	HGNC:30576	ENSG00000182551	Q9BV57	Acireductone dioxygenase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPS7	Small ribosomal subunit protein eS7	Component of the small ribosomal subunit.
ADI1	Acireductone dioxygenase	Catalyzes 2 different reactions between oxygen and the acireductone 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene) depending upon the metal bound in the active site.

Protein-family classification

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

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPS7	Other/Unknown	no		Ribosomal_eS7, Ribosomal_eS7_CS
ADI1	Enzyme (other)	yes	1.13.11.53	ARD, RmlC_Cupin_sf, RmlC-like_jellyroll

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
left ovary	1
ovary	1
primordial germ cell in gonad	1
adult mammalian kidney	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPS7	134	ubiquitous	marker	primordial germ cell in gonad, ovary, left ovary
ADI1	134	ubiquitous	marker	right lobe of liver, liver, adult mammalian kidney

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADI1	1,019
RPS7	1,018

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPS7	P62081	212
ADI1	Q9BV57	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 53. 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
Metabolism of amino acids and derivatives	2	67.6×	0.012	RPS7, ADI1
Methionine salvage pathway	1	951.7×	0.028	ADI1
Sulfur amino acid metabolism	1	285.5×	0.028	ADI1
Eukaryotic Translation Initiation	1	154.3×	0.028	RPS7
Cap-dependent Translation Initiation	1	154.3×	0.028	RPS7
SARS-CoV-1 modulates host translation machinery	1	154.3×	0.028	RPS7
Eukaryotic Translation Elongation	1	139.3×	0.028	RPS7
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1	135.9×	0.028	RPS7
Nonsense-Mediated Decay (NMD)	1	116.5×	0.028	RPS7
SARS-CoV-2 modulates host translation machinery	1	112.0×	0.028	RPS7
Influenza Viral RNA Transcription and Replication	1	107.7×	0.028	RPS7
Formation of the ternary complex, and subsequently, the 43S complex	1	107.7×	0.028	RPS7
Selenoamino acid metabolism	1	98.5×	0.028	RPS7
Translation initiation complex formation	1	95.2×	0.028	RPS7
Ribosomal scanning and start codon recognition	1	95.2×	0.028	RPS7
rRNA modification in the nucleus and cytosol	1	93.6×	0.028	RPS7
Influenza Infection	1	87.8×	0.028	RPS7
SARS-CoV-1-host interactions	1	87.8×	0.028	RPS7
Cellular response to starvation	1	82.8×	0.028	RPS7
rRNA processing in the nucleus and cytosol	1	80.4×	0.028	RPS7
rRNA processing	1	73.2×	0.028	RPS7
SARS-CoV-1 Infection	1	71.4×	0.028	RPS7
Peptide chain elongation	1	63.4×	0.028	RPS7
Viral mRNA Translation	1	63.4×	0.028	RPS7
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	1	62.8×	0.028	RPS7
Signaling by ROBO receptors	1	62.1×	0.028	RPS7
Selenocysteine synthesis	1	60.1×	0.028	RPS7
Eukaryotic Translation Termination	1	60.1×	0.028	RPS7
SARS-CoV-2-host interactions	1	59.5×	0.028	RPS7
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	1	58.9×	0.028	RPS7

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete L-methionine salvage from methylthioadenosine	1	1685.2×	0.002	ADI1
L-methionine metabolic process	1	1404.3×	0.002	ADI1
positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	1404.3×	0.002	RPS7
neural crest cell differentiation	1	766.0×	0.003	RPS7
negative regulation of ubiquitin-dependent protein catabolic process	1	421.3×	0.005	RPS7
ribosomal small subunit biogenesis	1	113.9×	0.013	RPS7
neural tube closure	1	93.6×	0.013	RPS7
cytoplasmic translation	1	92.6×	0.013	RPS7
rRNA processing	1	70.8×	0.016	RPS7
translation	1	51.4×	0.019	RPS7

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) 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
RPS7	GENTAMICIN SULFATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RPS7	1	4
ADI1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPS7

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
RPS7	96	Binding:96
ADI1	1	ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ADI1	1.13.11.53, 1.13.11.54	acireductone dioxygenase (Ni2+-requiring), acireductone dioxygenase [iron(II)-requiring]

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	RPS7

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RPS7
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	ADI1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
ADI1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.