Elliptocytosis 3

Summary

Elliptocytosis 3 (MONDO:0054780) is a disease caused by SPTB (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SPTB (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 42

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	elliptocytosis 3
Mondo ID	MONDO:0054780
MeSH	C566678
OMIM	617948
UMLS	C1866810
MedGen	357139
GARD	0016273
Is cancer (heuristic)	no

Also known as: anemia, neonatal hemolytic, fatal or near-fatal · EL3 · elliptocytosis 3 · elliptocytosis-3

Data availability: 42 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › normocytic anemia › hemolytic anemia › hereditary elliptocytosis › elliptocytosis 3

Related subtypes (4): elliptocytosis 2, southeast Asian ovalocytosis, hemolytic anemia with thermal sensitivity of red cells, elliptocytosis 1

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

42 retrieved; paginated sample, class counts are floors:

14 uncertain significance, 8 pathogenic, 7 likely pathogenic, 6 conflicting classifications of pathogenicity, 4 pathogenic/likely pathogenic, 2 benign/likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
12832	NM_001355436.2(SPTB):c.6269+3G>T	SPTB	Pathogenic	no assertion criteria provided
12833	NM_001355436.2(SPTB):c.6135_6136dup (p.Lys2046fs)	SPTB	Pathogenic	no assertion criteria provided
12834	NM_001355436.2(SPTB):c.6177del (p.Ser2060fs)	SPTB	Pathogenic	no assertion criteria provided
12836	NM_001355436.2(SPTB):c.6053C>G (p.Ala2018Gly)	SPTB	Pathogenic	no assertion criteria provided
12837	NM_001355436.2(SPTB):c.6055T>C (p.Ser2019Pro)	SPTB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12840	NM_001355436.2(SPTB):c.6191G>C (p.Arg2064Pro)	SPTB	Pathogenic	no assertion criteria provided
12843	NM_001355436.2(SPTB):c.5266C>T (p.Arg1756Ter)	SPTB	Pathogenic	criteria provided, multiple submitters, no conflicts
1325130	NM_001355436.2(SPTB):c.6224A>G (p.Glu2075Gly)	SPTB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1339570	NM_001355436.2(SPTB):c.3818_3832delinsGT (p.Asn1273fs)	SPTB	Pathogenic	no assertion criteria provided
1676993	NM_001355436.2(SPTB):c.2521C>T (p.Gln841Ter)	SPTB	Pathogenic	criteria provided, multiple submitters, no conflicts
1996965	NM_001355436.2(SPTB):c.3088G>T (p.Glu1030Ter)	SPTB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
544811	NM_001355436.2(SPTB):c.647G>A (p.Arg216Gln)	SPTB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12831	NM_001355436.2(SPTB):c.6157G>C (p.Ala2053Pro)	SPTB	Likely pathogenic	criteria provided, single submitter
3338264	NM_001355436.2(SPTB):c.6175G>C (p.Ala2059Pro)	SPTB	Likely pathogenic	criteria provided, single submitter
3382350	NM_001355436.2(SPTB):c.3114delinsAAACAT (p.His1038fs)	SPTB	Likely pathogenic	criteria provided, single submitter
3383058	NM_001355436.2(SPTB):c.3352C>T (p.Gln1118Ter)	SPTB	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3576659	NM_001355436.2(SPTB):c.3262del (p.Asp1088fs)	SPTB	Likely pathogenic	criteria provided, single submitter
3629453	NM_001355436.2(SPTB):c.6219+1G>C	SPTB	Likely pathogenic	criteria provided, single submitter
4533219	NM_001355436.2(SPTB):c.2333dup (p.Arg779fs)	SPTB	Likely pathogenic	criteria provided, single submitter
1028696	NM_001355436.2(SPTB):c.4105A>G (p.Lys1369Glu)	SPTB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1683563	NM_001355436.2(SPTB):c.3764+8C>T	SPTB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
279902	NM_001355436.2(SPTB):c.5651C>T (p.Ala1884Val)	SPTB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
313705	NM_001355436.2(SPTB):c.5915G>A (p.Arg1972Gln)	SPTB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
313761	NM_001355436.2(SPTB):c.1606G>A (p.Asp536Asn)	SPTB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
313785	NM_001355436.2(SPTB):c.26A>C (p.Asn9Thr)	SPTB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028697	NM_001355436.2(SPTB):c.6181T>G (p.Trp2061Gly)	SPTB	Uncertain significance	criteria provided, single submitter
1687184	NM_001355436.2(SPTB):c.6223G>C (p.Glu2075Gln)	SPTB	Uncertain significance	criteria provided, multiple submitters, no conflicts
2395920	NM_001355436.2(SPTB):c.1509G>C (p.Lys503Asn)	SPTB	Uncertain significance	criteria provided, multiple submitters, no conflicts
2466517	NM_001355436.2(SPTB):c.2593G>A (p.Gly865Arg)	SPTB	Uncertain significance	criteria provided, single submitter
2507948	NM_001355436.2(SPTB):c.5899G>A (p.Glu1967Lys)	SPTB	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · 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
SPTB	Strong	Autosomal recessive	elliptocytosis 3	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SPTB	Orphanet:288	Hereditary elliptocytosis
SPTB	Orphanet:822	Hereditary spherocytosis

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
SPTB	HGNC:11274	ENSG00000070182	P11277	Spectrin beta chain, erythrocytic	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SPTB	Spectrin beta chain, erythrocytic	Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane.

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)
SPTB	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat

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
gastrocnemius	1
hindlimb stylopod muscle	1
muscle of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SPTB	220	broad	marker	gastrocnemius, hindlimb stylopod muscle, muscle of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SPTB	1,079

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SPTB	P11277	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. 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
Interaction between L1 and Ankyrins	1	368.4×	0.022	SPTB
NCAM signaling for neurite out-growth	1	271.9×	0.022	SPTB
ER to Golgi Anterograde Transport	1	132.8×	0.022	SPTB
MAPK1/MAPK3 signaling	1	131.3×	0.022	SPTB
L1CAM interactions	1	120.2×	0.022	SPTB
COPI-mediated anterograde transport	1	109.8×	0.022	SPTB
MAPK family signaling cascades	1	102.9×	0.022	SPTB
Transport to the Golgi and subsequent modification	1	102.9×	0.022	SPTB
RAF/MAP kinase cascade	1	61.1×	0.030	SPTB
Asparagine N-linked glycosylation	1	60.1×	0.030	SPTB
Axon guidance	1	45.1×	0.035	SPTB
Nervous system development	1	42.9×	0.035	SPTB
Membrane Trafficking	1	37.1×	0.037	SPTB
Vesicle-mediated transport	1	34.8×	0.037	SPTB
Post-translational protein modification	1	19.2×	0.063	SPTB
Developmental Biology	1	14.5×	0.078	SPTB
Metabolism of proteins	1	12.4×	0.086	SPTB
Signal Transduction	1	10.2×	0.098	SPTB

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
actin filament capping	1	1532.0×	0.001	SPTB
modification of postsynaptic actin cytoskeleton	1	1404.3×	0.001	SPTB
actin cytoskeleton organization	1	79.1×	0.013	SPTB

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SPTB	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	SPTB

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)
SPTB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.