Erythrocytosis, familial, 6

Summary

Erythrocytosis, familial, 6 (MONDO:0054801) is a disease caused by HBB (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: HBB (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 148

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	erythrocytosis, familial, 6
Mondo ID	MONDO:0054801
OMIM	617980
DOID	DOID:0111632
UMLS	C4693822
MedGen	1634191
GARD	0025978
Is cancer (heuristic)	no

Also known as: ECYT6 · erythrocytosis 6

Data availability: 148 ClinVar variants · 3 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, 6

Related subtypes (7): primary familial polycythemia due to EPO receptor mutation, acquired polycythemia vera, Chuvash polycythemia, erythrocytosis, familial, 3, erythrocytosis, familial, 4, erythrocytosis, familial, 5, 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

148 retrieved; paginated sample, class counts are floors:

50 pathogenic, 24 uncertain significance, 24 pathogenic/likely pathogenic, 21 pathogenic; other, 18 conflicting classifications of pathogenicity, 6 likely pathogenic, 2 benign/likely benign, 1 pathogenic/likely pathogenic; other, 1 benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
15096	NM_000518.5(HBB):c.435G>C (p.Lys145Asn)	HBB	Pathogenic	criteria provided, single submitter
15116	NM_000518.4(HBB):c.302C>T (p.Pro101Leu)	HBB	Pathogenic; other	no assertion criteria provided
15117	NM_000518.4(HBB):c.206T>A (p.Leu69His)	HBB	Pathogenic; other	no assertion criteria provided
15126	NM_000518.4(HBB):c.19G>A (p.Glu7Lys)	HBB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
15134	NM_000518.4(HBB):c.299A>T (p.Asp100Val)	HBB	Pathogenic; other	no assertion criteria provided
15144	NM_000518.4(HBB):c.440A>T (p.His147Leu)	HBB	Pathogenic; other	no assertion criteria provided
15147	NM_000518.4(HBB):c.269G>A (p.Ser90Asn)	HBB	Pathogenic/Likely pathogenic; other	no assertion criteria provided
15152	NM_000518.4(HBB):c.364G>C (p.Glu122Gln)	HBB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
15161	NM_000518.5(HBB):c.79G>A (p.Glu27Lys)	HBB	Pathogenic	criteria provided, multiple submitters, no conflicts
15192	NM_000518.5(HBB):c.312C>G (p.Phe104Leu)	HBB	Pathogenic; other	no assertion criteria provided
15200	NM_000518.4(HBB):c.439C>G (p.His147Asp)	HBB	Pathogenic; other	no assertion criteria provided
15204	NM_000518.4(HBB):c.299A>G (p.Asp100Gly)	HBB	Pathogenic; other	no assertion criteria provided
15234	NM_000518.4(HBB):c.92G>C (p.Arg31Thr)	HBB	Pathogenic	criteria provided, multiple submitters, no conflicts
15236	NM_000518.4(HBB):c.298G>A (p.Asp100Asn)	HBB	Pathogenic; other	no assertion criteria provided
15239	NM_000518.5(HBB):c.82G>T (p.Ala28Ser)	HBB	Pathogenic	criteria provided, multiple submitters, no conflicts
15250	Hb Little Rock	HBB	Pathogenic	no assertion criteria provided
15259	NM_000518.5(HBB):c.294C>R (p.His98Gln)	HBB	Pathogenic; other	no assertion criteria provided
15265	NM_000518.5(HBB):c.438T>A (p.Tyr146Ter)	HBB	Pathogenic; other	no assertion criteria provided
15292	NM_000518.4(HBB):c.364G>A (p.Glu122Lys)	HBB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
15300	NM_000518.5(HBB):c.61G>A (p.Val21Met)	HBB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
15306	NM_000518.4(HBB):c.70G>T (p.Val24Phe)	HBB	Pathogenic; other	no assertion criteria provided
15315	NM_000518.4(HBB):c.299A>C (p.Asp100Ala)	HBB	Pathogenic; other	no assertion criteria provided
15317	NM_000518.5(HBB):c.306G>C (p.Glu102Asp)	HBB	Pathogenic; other	no assertion criteria provided
15319	NM_000518.5(HBB):c.249G>Y (p.Lys83Asn)	HBB	Pathogenic; other	no assertion criteria provided
15321	NM_000518.4(HBB):c.248A>C (p.Lys83Thr)	HBB	Pathogenic; other	no assertion criteria provided
15322	NM_000518.5(HBB):c.437A>G (p.Tyr146Cys)	HBB	Pathogenic	criteria provided, multiple submitters, no conflicts
15333	NM_000518.5(HBB):c.20A>T (p.Glu7Val)	HBB	Pathogenic	criteria provided, multiple submitters, no conflicts
15339	NM_000518.5(HBB):c.421G>A (p.Ala141Thr)	HBB	Pathogenic; other	no assertion criteria provided
15342	NM_000518.5(HBB):c.328G>A (p.Val110Met)	HBB	Pathogenic	criteria provided, multiple submitters, no conflicts
15365	NM_000518.5(HBB):c.431A>C (p.His144Pro)	HBB	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 33 · Orphanet: 29 · 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
HBB	Strong	Autosomal dominant	erythrocytosis, familial, 6	33

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HBB	Orphanet:2132	Hemoglobin C disease
HBB	Orphanet:2133	Hemoglobin E disease
HBB	Orphanet:231214	Beta-thalassemia major
HBB	Orphanet:231222	Beta-thalassemia intermedia
HBB	Orphanet:231226	Unstable beta globin chain variant disease
HBB	Orphanet:231237	Delta-beta-thalassemia
HBB	Orphanet:231242	Hemoglobin C-beta-thalassemia syndrome
HBB	Orphanet:231249	Hemoglobin E-beta-thalassemia syndrome
HBB	Orphanet:232	Sickle cell anemia
HBB	Orphanet:247511	Autosomal dominant secondary polycythemia
HBB	Orphanet:251365	Sickle cell S-C disease
HBB	Orphanet:251370	Sickle cell S-D Punjab disease
HBB	Orphanet:251375	Sickle cell S-E disease
HBB	Orphanet:251380	Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
HBB	Orphanet:330041	Hemoglobin M disease
HBB	Orphanet:46532	Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome
HBB	Orphanet:695140	Sickle cell-beta zero-thalassemia
HBB	Orphanet:695147	Sickle cell-beta plus-thalassemia
HBB	Orphanet:699822	Sickle cell S-Lepore disease
HBB	Orphanet:700090	Sickle cell S-O Arab disease
HBB	Orphanet:700107	Sickle cell S-other specified hemoglobin variant
HBB	Orphanet:700111	Homozygous hemoglobin O Arab disease
HBB	Orphanet:715125	Hemoglobin E-beta-thalassemia intermedia
HBB	Orphanet:715128	Hemoglobin E-beta-thalassemia major
HBB	Orphanet:715135	Hemoglobin Lepore-beta-thalassemia intermedia
HBB	Orphanet:715140	Hemoglobin Lepore-beta-thalassemia major
HBB	Orphanet:715143	Heterozygous beta-thalassemia intermedia with supernumerary alpha-globin gene
HBB	Orphanet:715157	Low oxygen affinity beta chain hemoglobin disease
HBB	Orphanet:90039	Hemoglobin D disease

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
HBB	HGNC:4827	ENSG00000244734	P68871	Hemoglobin subunit beta	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HBB	Hemoglobin subunit beta	Involved in oxygen transport from the lung to the various peripheral tissues.

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)
HBB	Other/Unknown	no		Globin, Hemoglobin_b, Globin-like_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
monocyte	1
trabecular bone tissue	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HBB	284	broad	marker	monocyte, trabecular bone tissue, vena cava

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HBB	454

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HBB	P68871	350

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Heme assimilation	1	3806.7×	0.003	HBB
Erythrocytes take up oxygen and release carbon dioxide	1	1268.9×	0.003	HBB
Erythrocytes take up carbon dioxide and release oxygen	1	878.5×	0.003	HBB
Scavenging of heme from plasma	1	878.5×	0.003	HBB
Chaperone Mediated Autophagy	1	496.5×	0.004	HBB
Late endosomal microautophagy	1	326.3×	0.005	HBB
Heme signaling	1	215.5×	0.007	HBB
Cytoprotection by HMOX1	1	184.2×	0.007	HBB
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.017	HBB
Neutrophil degranulation	1	23.1×	0.043	HBB

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
nitric oxide transport	1	3370.4×	0.002	HBB
cellular oxidant detoxification	1	1872.4×	0.002	HBB
renal absorption	1	1685.2×	0.002	HBB
carbon dioxide transport	1	1296.3×	0.002	HBB
oxygen transport	1	1053.2×	0.002	HBB
hydrogen peroxide catabolic process	1	674.1×	0.003	HBB
blood vessel diameter maintenance	1	624.1×	0.003	HBB
erythrocyte development	1	526.6×	0.003	HBB
response to hydrogen peroxide	1	468.1×	0.003	HBB
positive regulation of nitric oxide biosynthetic process	1	455.5×	0.003	HBB
platelet aggregation	1	337.0×	0.004	HBB
regulation of blood pressure	1	221.7×	0.005	HBB
inflammatory response	1	37.7×	0.027	HBB

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
HBB	CANDESARTAN CILEXETIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HBB	23	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CANDESARTAN CILEXETIL	4	HBB
MECHLORETHAMINE HYDROCHLORIDE	4	HBB
PHENAZOPYRIDINE HYDROCHLORIDE	4	HBB
MERCAPTOPURINE ANHYDROUS	4	HBB
AZACITIDINE	4	HBB
AZATHIOPRINE	4	HBB
TOPOTECAN HYDROCHLORIDE	4	HBB
ACYCLOVIR	4	HBB
FLUOROURACIL	4	HBB
RAUWOLFIA SERPENTINA	4	HBB
HYDROQUINONE	4	HBB
MENADIONE	4	HBB
THIOTEPA	4	HBB
THIOGUANINE	4	HBB
RESERPINE	4	HBB
CURCUMIN	3	HBB
HYDROXYCAMPTOTHECIN	3	HBB
MOLIBRESIB	2	HBB
FISETIN	2	HBB
TEROXIRONE	2	HBB
5-FLUOROURIDINE	2	HBB
ELLAGIC ACID	2	HBB
BAICALEIN	2	HBB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
HBB	68	Binding:50, Functional:18

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

23 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)
CANDESARTAN CILEXETIL	4	HBB
MECHLORETHAMINE HYDROCHLORIDE	4	HBB
PHENAZOPYRIDINE HYDROCHLORIDE	4	HBB
MERCAPTOPURINE ANHYDROUS	4	HBB
AZACITIDINE	4	HBB
AZATHIOPRINE	4	HBB
TOPOTECAN HYDROCHLORIDE	4	HBB
ACYCLOVIR	4	HBB
FLUOROURACIL	4	HBB
RAUWOLFIA SERPENTINA	4	HBB
HYDROQUINONE	4	HBB
MENADIONE	4	HBB
THIOTEPA	4	HBB
THIOGUANINE	4	HBB
RESERPINE	4	HBB
CURCUMIN	3	HBB
HYDROXYCAMPTOTHECIN	3	HBB
MOLIBRESIB	2	HBB
FISETIN	2	HBB
TEROXIRONE	2	HBB
5-FLUOROURIDINE	2	HBB
ELLAGIC ACID	2	HBB
BAICALEIN	2	HBB

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	HBB
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: 0.