Macrocytic anemia

Summary

Macrocytic anemia (MONDO:0002281) is a disease with 3 cohort genes and 1 clinical trial.

At a glance

• Cohort genes: 3
• ClinVar variants: 2
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	macrocytic anemia
Mondo ID	MONDO:0002281
MeSH	D000748
DOID	DOID:2361
NCIT	C34381
SNOMED CT	83414005
UMLS	C0002886
MedGen	1920
Is cancer (heuristic)	no

Also known as: anaemia macrocytic · anemia macrocytic · D22S676 · D22S750 · macrocytic anaemia (disease) · macrocytic anaemia of unspecified cause · macrocytic Anemia · macrocytic anemia · macrocytic anemia (disease) · macrocytic anemia of unspecified cause

Data availability: 2 ClinVar variants · 1 HPO phenotype.

Disease family

An umbrella term covering 2 Mondo subtypes.

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

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

Subtypes (2): megaloblastic anemia, myelodysplastic syndrome associated with isolated del(5q)

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

2 retrieved; paginated sample, class counts are floors:

1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
916674	NM_198253.3(TERT):c.2812C>T (p.Arg938Trp)	TERT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3233357	NM_001035006.5(RPL17):c.452del (p.Thr151fs)	RPL17	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPL17	HGNC:10307	ENSG00000265681	P18621	Large ribosomal subunit protein uL22	clinvar
RPL23	HGNC:10316	ENSG00000125691	P62829	Large ribosomal subunit protein uL14	clinvar
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPL17	Large ribosomal subunit protein uL22	Component of the large ribosomal subunit.
RPL23	Large ribosomal subunit protein uL14	Component of the large ribosomal subunit.
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPL17	Other/Unknown	no		Ribosomal_uL22, Ribosomal_uL22_euk_arc, Ribosomal_uL22_CS
RPL23	Other/Unknown	no		Ribosomal_uL14, Ribosomal_uL14_CS, Ribosomal_uL14_sf
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left ovary	2
right ovary	2
ovary	1
ganglionic eminence	1
olfactory bulb	1
stromal cell of endometrium	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPL17	134	ubiquitous	marker	left ovary, ovary, right ovary
RPL23	210	ubiquitous	marker	ganglionic eminence, left ovary, right ovary
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TERT	5,717
RPL17	5,372
RPL23	1,303

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPL17	P18621	195
RPL23	P62829	190
TERT	O14746	23

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 29. Enrichment computed across 3 evidence-associated genes (3 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 3 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	2	84.6×	6e-04	RPL17, RPL23
Viral mRNA Translation	2	84.6×	6e-04	RPL17, RPL23
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	2	83.7×	6e-04	RPL17, RPL23
Selenocysteine synthesis	2	80.1×	6e-04	RPL17, RPL23
Eukaryotic Translation Termination	2	80.1×	6e-04	RPL17, RPL23
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	2	78.5×	6e-04	RPL17, RPL23
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	2	78.5×	6e-04	RPL17, RPL23
Formation of a pool of free 40S subunits	2	74.6×	6e-04	RPL17, RPL23
Response of EIF2AK4 (GCN2) to amino acid deficiency	2	73.9×	6e-04	RPL17, RPL23
Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide	2	71.2×	6e-04	RPL17, RPL23
L13a-mediated translational silencing of Ceruloplasmin expression	2	67.4×	6e-04	RPL17, RPL23
SRP-dependent cotranslational protein targeting to membrane	2	66.8×	6e-04	RPL17, RPL23
GTP hydrolysis and joining of the 60S ribosomal subunit	2	66.8×	6e-04	RPL17, RPL23
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	2	65.1×	6e-04	RPL17, RPL23
Regulation of expression of SLITs and ROBOs	2	46.1×	0.001	RPL17, RPL23
Major pathway of rRNA processing in the nucleolus and cytosol	2	41.1×	0.001	RPL17, RPL23
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	543.8×	0.003	TERT
Extension of Telomeres	1	200.3×	0.008	TERT
Telomere Extension By Telomerase	1	152.3×	0.010	TERT
Telomere Maintenance	1	122.8×	0.012	TERT
Chromosome Maintenance	1	70.5×	0.019	TERT
MITF-M-dependent gene expression	1	60.4×	0.022	TERT
Formation of the beta-catenin:TCF transactivating complex	1	40.1×	0.030	TERT
TCF dependent signaling in response to WNT	1	39.2×	0.030	TERT
MITF-M-regulated melanocyte development	1	38.1×	0.030	TERT
Signaling by WNT	1	37.3×	0.030	TERT
Cell Cycle	1	12.0×	0.087	TERT
Developmental Biology	1	4.8×	0.200	TERT
Signal Transduction	1	3.4×	0.267	TERT

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 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	5617.3×	0.002	TERT
DNA strand elongation	1	5617.3×	0.002	TERT
siRNA transcription	1	5617.3×	0.002	TERT
positive regulation of transdifferentiation	1	5617.3×	0.002	TERT
cytoplasmic translation	2	123.5×	0.002	RPL17, RPL23
RNA-templated DNA biosynthetic process	1	2808.7×	0.002	TERT
positive regulation of hair cycle	1	2808.7×	0.002	TERT
translation	2	68.5×	0.002	RPL17, RPL23
protein-DNA complex disassembly	1	1872.4×	0.003	RPL23
regulation of G1 to G0 transition	1	1404.3×	0.003	RPL23
ribosomal protein import into nucleus	1	1123.5×	0.003	RPL23
positive regulation of protein localization to nucleolus	1	936.2×	0.004	TERT
establishment of protein localization to telomere	1	702.2×	0.005	TERT
siRNA processing	1	624.1×	0.005	TERT
telomere maintenance via recombination	1	510.7×	0.006	TERT
G1 to G0 transition	1	468.1×	0.006	RPL23
positive regulation of signal transduction by p53 class mediator	1	401.2×	0.006	RPL23
replicative senescence	1	330.4×	0.007	TERT
positive regulation of vascular associated smooth muscle cell migration	1	330.4×	0.007	TERT
negative regulation of ubiquitin-dependent protein catabolic process	1	280.9×	0.008	RPL23
DNA biosynthetic process	1	267.5×	0.008	TERT
telomere maintenance via telomerase	1	244.2×	0.008	TERT
response to cadmium ion	1	244.2×	0.008	TERT
negative regulation of cellular senescence	1	216.1×	0.008	TERT
positive regulation of stem cell proliferation	1	175.5×	0.010	TERT
negative regulation of endothelial cell apoptotic process	1	165.2×	0.010	TERT
positive regulation of D-glucose import across plasma membrane	1	151.8×	0.010	TERT
positive regulation of vascular associated smooth muscle cell proliferation	1	144.0×	0.011	TERT
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	137.0×	0.011	TERT
positive regulation of G1/S transition of mitotic cell cycle	1	133.8×	0.011	TERT

Therapeutics

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 0

Druggability breadth: 3 of 3 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
RPL17	GENTAMICIN SULFATE
RPL23	GENTAMICIN SULFATE
TERT	BERBERINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TERT	10	4
RPL17	1	4
RPL23	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPL17, RPL23
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

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
RPL17	90	Binding:90
RPL23	90	Binding:90

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: 3; 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)
GENTAMICIN SULFATE	4	RPL17, RPL23
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

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	RPL17, RPL23, TERT
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06223854	Not specified	COMPLETED	Acceptability and Nutritional Impact of Double-fortified Salt Containing Iodine and Folic Acid