Elliptocytosis 2

Summary

Elliptocytosis 2 (MONDO:0007533) is a disease caused by SPTA1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: SPTA1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 308

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	elliptocytosis 2
Mondo ID	MONDO:0007533
MeSH	C565058
OMIM	130600
UMLS	C1851741
MedGen	343643
GARD	0015064
Is cancer (heuristic)	no

Also known as: EL2 · elliptocytosis 2 · elliptocytosis type 2 · elliptocytosis-2 · hereditary elliptocytosis caused by mutation in SPTA1 · SPTA1 hereditary elliptocytosis

Data availability: 308 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 2

Related subtypes (22): congenital nonspherocytic hemolytic anemia, 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, elliptocytosis 1, 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

308 retrieved; paginated sample, class counts are floors:

127 conflicting classifications of pathogenicity, 109 uncertain significance, 38 benign, 16 benign/likely benign, 9 pathogenic/likely pathogenic, 8 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1030628	NM_003126.4(SPTA1):c.3163C>T (p.Gln1055Ter)	SPTA1	Pathogenic	criteria provided, single submitter
1030630	NM_003126.4(SPTA1):c.4339-99C>T	SPTA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1030633	NM_003126.4(SPTA1):c.6813_6814del (p.Glu2271fs)	SPTA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1163172	NM_003126.4(SPTA1):c.178C>T (p.Arg60Ter)	SPTA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12844	NM_003126.4(SPTA1):c.779T>C (p.Leu260Pro)	SPTA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12849	NM_003126.4(SPTA1):c.135G>T (p.Arg45Ser)	SPTA1	Pathogenic	no assertion criteria provided
12852	NM_003126.4(SPTA1):c.121C>T (p.Arg41Trp)	SPTA1	Pathogenic	no assertion criteria provided
12853	NM_003126.4(SPTA1):c.83G>T (p.Arg28Leu)	SPTA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12854	NM_003126.4(SPTA1):c.82C>A (p.Arg28Ser)	SPTA1	Pathogenic	criteria provided, multiple submitters, no conflicts
12855	NM_003126.4(SPTA1):c.82C>T (p.Arg28Cys)	SPTA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12856	NM_003126.4(SPTA1):c.83G>A (p.Arg28His)	SPTA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12860	NM_003126.4(SPTA1):c.2465-1G>A	SPTA1	Pathogenic	no assertion criteria provided
12861	NG_011474.1:g.11070_11071insSVAelement	SPTA1	Pathogenic	no assertion criteria provided
1343229	NM_003126.4(SPTA1):c.4519C>T (p.Arg1507Ter)	SPTA1	Pathogenic	criteria provided, single submitter
561993	NM_003126.4(SPTA1):c.4975C>T (p.Arg1659Ter)	SPTA1	Pathogenic	criteria provided, multiple submitters, no conflicts
801565	NM_003126.4(SPTA1):c.1833+1G>A	SPTA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
931603	NM_003126.4(SPTA1):c.2320C>T (p.Arg774Ter)	SPTA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382312	NM_003126.4(SPTA1):c.2167C>T (p.Gln723Ter)	SPTA1	Likely pathogenic	criteria provided, single submitter
292934	NM_003126.4(SPTA1):c.*68C>G	OR10Z1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
12847	NM_003126.4(SPTA1):c.460_462dup (p.Leu155dup)	SPTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
12848	NM_003126.4(SPTA1):c.781T>C (p.Ser261Pro)	SPTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
12850	NM_003126.4(SPTA1):c.137G>T (p.Gly46Val)	SPTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
12857	NM_003126.4(SPTA1):c.620T>C (p.Leu207Pro)	SPTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
12859	NM_003126.4(SPTA1):c.2373C>A (p.Asp791Glu)	SPTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
258915	NM_003126.4(SPTA1):c.1078A>T (p.Thr360Ser)	SPTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
258918	NM_003126.4(SPTA1):c.1958A>G (p.Tyr653Cys)	SPTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
258928	NM_003126.4(SPTA1):c.3477+15C>T	SPTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
258933	NM_003126.4(SPTA1):c.3960C>T (p.Asp1320=)	SPTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
258938	NM_003126.4(SPTA1):c.4453C>T (p.Leu1485Phe)	SPTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
258940	NM_003126.4(SPTA1):c.4490G>A (p.Gly1497Glu)	SPTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · 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
SPTA1	Strong	Autosomal dominant	elliptocytosis 2	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SPTA1	Orphanet:288	Hereditary elliptocytosis
SPTA1	Orphanet:822	Hereditary spherocytosis

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SPTA1	HGNC:11272	ENSG00000163554	P02549	Spectrin alpha chain, erythrocytic 1	gencc,clinvar
OR10Z1	HGNC:14996	ENSG00000198967	Q8NGY1	Olfactory receptor 10Z1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SPTA1	Spectrin alpha chain, erythrocytic 1	Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane.
OR10Z1	Olfactory receptor 10Z1	Odorant receptor.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
GPCR	1	12.0×	0.112
Scaffold/PPI	1	8.6×	0.112

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SPTA1	Scaffold/PPI	no		SH3_domain, Spectrin_repeat, EF_hand_dom
OR10Z1	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bone marrow	2
bone marrow cell	2
trabecular bone tissue	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SPTA1	147	tissue_specific	marker	trabecular bone tissue, bone marrow, bone marrow cell
OR10Z1	36		marker	male germ line stem cell (sensu Vertebrata) in testis, bone marrow, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SPTA1	1,551
OR10Z1	132

Intra-cohort edges

A	B	Sources
OR10Z1	SPTA1	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SPTA1	P02549	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
OR10Z1	Q8NGY1	85.94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 2 evidence-associated genes (2 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 2 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	184.2×	0.046	SPTA1
NCAM signaling for neurite out-growth	1	135.9×	0.046	SPTA1
ER to Golgi Anterograde Transport	1	66.4×	0.046	SPTA1
MAPK1/MAPK3 signaling	1	65.6×	0.046	SPTA1
L1CAM interactions	1	60.1×	0.046	SPTA1
COPI-mediated anterograde transport	1	54.9×	0.046	SPTA1
MAPK family signaling cascades	1	51.4×	0.046	SPTA1
Transport to the Golgi and subsequent modification	1	51.4×	0.046	SPTA1
RAF/MAP kinase cascade	1	30.5×	0.063	SPTA1
Asparagine N-linked glycosylation	1	30.1×	0.063	SPTA1
Axon guidance	1	22.6×	0.073	SPTA1
Nervous system development	1	21.5×	0.073	SPTA1
Membrane Trafficking	1	18.5×	0.077	SPTA1
Vesicle-mediated transport	1	17.4×	0.077	SPTA1
Expression and translocation of olfactory receptors	1	14.1×	0.088	OR10Z1
Post-translational protein modification	1	9.6×	0.121	SPTA1
Developmental Biology	1	7.2×	0.149	SPTA1
Metabolism of proteins	1	6.2×	0.164	SPTA1
Signal Transduction	1	5.1×	0.187	SPTA1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
porphyrin-containing compound biosynthetic process	1	2106.5×	0.004	SPTA1
lymphocyte homeostasis	1	936.2×	0.004	SPTA1
actin filament capping	1	766.0×	0.004	SPTA1
plasma membrane organization	1	443.5×	0.006	SPTA1
hemopoiesis	1	133.8×	0.013	SPTA1
positive regulation of T cell proliferation	1	129.6×	0.013	SPTA1
detection of chemical stimulus involved in sensory perception of smell	1	62.0×	0.019	OR10Z1
regulation of cell shape	1	61.5×	0.019	SPTA1
actin filament organization	1	59.3×	0.019	SPTA1
actin cytoskeleton organization	1	39.6×	0.025	SPTA1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
SPTA1	0	0
OR10Z1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	OR10Z1
E	Difficult family or no structure, no drug	1	SPTA1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SPTA1	0	—
OR10Z1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.