Elliptocytosis 1

Summary

Elliptocytosis 1 (MONDO:0012731) is a disease caused by EPB41 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: EPB41 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 112

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	elliptocytosis 1
Mondo ID	MONDO:0012731
MeSH	C567520
OMIM	611804
UMLS	C2678497
MedGen	394841
GARD	0015528
Is cancer (heuristic)	no

Also known as: EL1 · elliptocytosis 1 · elliptocytosis type 1 · elliptocytosis-1 · EPB41 hereditary elliptocytosis · hereditary elliptocytosis caused by mutation in EPB41

Data availability: 112 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › normocytic anemia › hemolytic anemia › familial hemolytic anemia › elliptocytosis 1

Related subtypes (22): congenital nonspherocytic hemolytic anemia, elliptocytosis 2, southeast Asian ovalocytosis, overhydrated hereditary stomatocytosis, cryohydrocytosis, dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, abetalipoproteinemia, hemolytic anemia due to diphosphoglycerate mutase deficiency, glycogen storage disease VII, cutaneous porphyria, hereditary cryohydrocytosis with reduced stomatin, familial pseudohyperkalemia, renal tubular acidosis, distal, 4, with hemolytic anemia, glycogen storage disease due to aldolase A deficiency, primary CD59 deficiency, triosephosphate isomerase deficiency, dehydrated hereditary stomatocytosis 2, Rh deficiency syndrome, hereditary spherocytosis, congenital dyserythropoietic anemia, X-linked congenital hemolytic anemia, hemolytic disease of fetus and newborn, RH-induced

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

112 retrieved; paginated sample, class counts are floors:

61 uncertain significance, 13 likely pathogenic, 9 conflicting classifications of pathogenicity, 9 likely benign, 7 pathogenic, 5 benign, 4 benign/likely benign, 4 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
16711	NM_203342.2(EPB41):c.-159_159del	EPB41	Pathogenic	no assertion criteria provided
16712	NM_004437.3(EPB41):c.1219_1587del	EPB41	Pathogenic	no assertion criteria provided
16713	NM_004437.3(EPB41):c.1219_1458del	EPB41	Pathogenic	no assertion criteria provided
16714	NM_001376013.1(EPB41):c.629T>G (p.Met210Arg)	EPB41	Pathogenic	no assertion criteria provided
16715	NM_001376013.1(EPB41):c.629T>C (p.Met210Thr)	EPB41	Pathogenic	no assertion criteria provided
1951469	NM_001376013.1(EPB41):c.1660C>T (p.Arg554Ter)	EPB41	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2633316	NM_001376013.1(EPB41):c.1411C>T (p.Arg471Ter)	EPB41	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2779958	NM_001376013.1(EPB41):c.2143C>T (p.Arg715Ter)	EPB41	Pathogenic	criteria provided, multiple submitters, no conflicts
3729024	NM_001376013.1(EPB41):c.993C>A (p.Tyr331Ter)	EPB41	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3766780	NM_001376013.1(EPB41):c.741del (p.Glu248fs)	EPB41	Pathogenic	criteria provided, single submitter
4081368	NM_001376013.1(EPB41):c.1952_1955del (p.Arg651fs)	EPB41	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1163136	NM_001376013.1(EPB41):c.1744dup (p.Thr582fs)	EPB41	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324333	NM_001376013.1(EPB41):c.712C>T (p.Arg238Ter)	EPB41	Likely pathogenic	criteria provided, single submitter
1324334	NM_001376013.1(EPB41):c.1175del (p.Lys392fs)	EPB41	Likely pathogenic	criteria provided, single submitter
1330707	NM_001376013.1(EPB41):c.2065A>T (p.Lys689Ter)	EPB41	Likely pathogenic	criteria provided, single submitter
2440049	NM_001376013.1(EPB41):c.1330dup (p.Arg444fs)	EPB41	Likely pathogenic	criteria provided, single submitter
2446433	NM_001376013.1(EPB41):c.768G>A (p.Trp256Ter)	EPB41	Likely pathogenic	criteria provided, single submitter
2690597	NM_001376013.1(EPB41):c.2085_2089del (p.Val696fs)	EPB41	Likely pathogenic	criteria provided, single submitter
3391109	NM_001376013.1(EPB41):c.902C>G (p.Thr301Arg)	EPB41	Likely pathogenic	criteria provided, single submitter
4081367	NM_001376013.1(EPB41):c.818del (p.Lys273fs)	EPB41	Likely pathogenic	criteria provided, single submitter
4081369	NM_001376013.1(EPB41):c.1295del (p.Phe432fs)	EPB41	Likely pathogenic	criteria provided, single submitter
4081370	NM_001376013.1(EPB41):c.1609A>T (p.Lys537Ter)	EPB41	Likely pathogenic	criteria provided, single submitter
4081371	NM_001376013.1(EPB41):c.1464-1del	EPB41	Likely pathogenic	criteria provided, single submitter
4685959	NM_001376013.1(EPB41):c.830-1G>T	EPB41	Likely pathogenic	criteria provided, single submitter
1163134	NM_001376013.1(EPB41):c.1331G>A (p.Arg444His)	EPB41	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1330981	NM_001376013.1(EPB41):c.1700G>A (p.Gly567Asp)	EPB41	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2428563	NM_001376013.1(EPB41):c.263A>G (p.Lys88Arg)	EPB41	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2441246	NM_001376013.1(EPB41):c.832G>A (p.Val278Ile)	EPB41	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2683706	NM_001376013.1(EPB41):c.172G>A (p.Gly58Arg)	EPB41	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2729755	NM_001376013.1(EPB41):c.786+3G>A	EPB41	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
EPB41	Definitive	Semidominant	elliptocytosis 1	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EPB41	Orphanet:288	Hereditary elliptocytosis

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
EPB41	HGNC:3377	ENSG00000159023	P11171	Protein 4.1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EPB41	Protein 4.1	Protein 4.1 is a major structural element of the erythrocyte membrane skeleton.

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)
EPB41	Other/Unknown	no		FERM_domain, Ez/rad/moesin-like, SAB_dom

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
cerebellar cortex	1
cerebellar hemisphere	1
trabecular bone tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EPB41	261	ubiquitous	marker	trabecular bone tissue, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EPB41	1,928

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EPB41	P11171	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Neurexins and neuroligins	1	196.9×	0.005	EPB41

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
regulation of intestinal absorption	1	8426.0×	8e-04	EPB41
positive regulation of protein localization to cell cortex	1	3370.4×	0.001	EPB41
regulation of calcium ion transport	1	802.5×	0.002	EPB41
cortical actin cytoskeleton organization	1	601.9×	0.002	EPB41
actomyosin structure organization	1	561.7×	0.002	EPB41
actin cytoskeleton organization	1	79.1×	0.015	EPB41
cell division	1	46.2×	0.022	EPB41

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
EPB41	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
EPB41	1	Binding:1

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	EPB41

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)
EPB41	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.