Erythrocytosis, familial, 5

Summary

Erythrocytosis, familial, 5 (MONDO:0033483) is a disease caused by EPO (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: EPO (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	erythrocytosis, familial, 5
Mondo ID	MONDO:0033483
OMIM	617907
DOID	DOID:0080290
UMLS	C4693552
MedGen	1638941
GARD	0025802
Is cancer (heuristic)	no

Also known as: ECYT5 · EPO familial polycythemia · erythrocytosis, familial, 5 · familial polycythemia caused by mutation in EPO

Data availability: 2 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › familial polycythemia › erythrocytosis, familial, 5

Related subtypes (7): primary familial polycythemia due to EPO receptor mutation, acquired polycythemia vera, Chuvash polycythemia, erythrocytosis, familial, 3, erythrocytosis, familial, 4, erythrocytosis, familial, 6, erythrocytosis, familial, 7

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:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
496593	NM_000799.4(EPO):c.33del (p.Trp11fs)	EPO	Pathogenic	no assertion criteria provided
496594	NM_000799.4(EPO):c.20del (p.Pro7fs)	EPO	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
EPO	Strong	Autosomal dominant	erythrocytosis, familial, 5	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EPO	Orphanet:247511	Autosomal dominant secondary polycythemia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EPO	HGNC:3415	ENSG00000130427	P01588	Erythropoietin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EPO	Erythropoietin	Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EPO	Other/Unknown	no		EPO_TPO, Erythroptn, 4_helix_cytokine-like_core

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	1
right lobe of liver	1
triceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EPO	73	tissue_specific	yes	right lobe of liver, triceps brachii, body of pancreas

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EPO	2,945

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EPO	P01588	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Erythropoietin activates Phospholipase C gamma (PLCG)	1	1631.4×	0.001	EPO
Erythropoietin activates STAT5	1	1631.4×	0.001	EPO
Signaling by Erythropoietin	1	1038.2×	0.001	EPO
Regulation of gene expression by Hypoxia-inducible Factor	1	951.7×	0.001	EPO
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)	1	951.7×	0.001	EPO
Erythropoietin activates RAS	1	761.3×	0.001	EPO

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of erythrocyte apoptotic process	1	16852.0×	0.002	EPO
negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress	1	4213.0×	0.002	EPO
negative regulation of calcium ion transport into cytosol	1	3370.4×	0.002	EPO
erythropoietin-mediated signaling pathway	1	2808.7×	0.002	EPO
hemoglobin biosynthetic process	1	2808.7×	0.002	EPO
myeloid cell apoptotic process	1	2106.5×	0.003	EPO
response to salt stress	1	1872.4×	0.003	EPO
cellular hyperosmotic response	1	1203.7×	0.003	EPO
response to dexamethasone	1	1203.7×	0.003	EPO
response to hyperoxia	1	1123.5×	0.003	EPO
response to vitamin A	1	1053.2×	0.003	EPO
positive regulation of Ras protein signal transduction	1	887.0×	0.003	EPO
erythrocyte maturation	1	842.6×	0.003	EPO
positive regulation of activated T cell proliferation	1	674.1×	0.003	EPO
response to electrical stimulus	1	648.1×	0.003	EPO
cell surface receptor signaling pathway via STAT	1	561.7×	0.003	EPO
blood circulation	1	510.7×	0.003	EPO
response to axon injury	1	510.7×	0.003	EPO
response to interleukin-1	1	510.7×	0.003	EPO
response to testosterone	1	468.1×	0.004	EPO
acute-phase response	1	421.3×	0.004	EPO
embryo implantation	1	351.1×	0.004	EPO
response to estrogen	1	343.9×	0.004	EPO
erythrocyte differentiation	1	267.5×	0.005	EPO
positive regulation of neuron differentiation	1	198.3×	0.007	EPO
positive regulation of neuron projection development	1	137.0×	0.009	EPO
response to lipopolysaccharide	1	124.8×	0.010	EPO
response to hypoxia	1	95.8×	0.012	EPO
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.013	EPO
positive regulation of cell population proliferation	1	33.6×	0.033	EPO

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EPO	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
EPO	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	EPO

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)
EPO	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.