SPTA1

Chr 1ADAR

spectrin alpha, erythrocytic 1

Also known as: EL2, HPP, HS3, SPH3, SPTA

NCBI Gene: 6708 ENSG00000163554 UniProt: P02549 OMIM: 182860

This gene encodes a member of a family of molecular scaffold proteins that link the plasma membrane to the actin cytoskeleton and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. The encoded protein is primarily composed of 22 spectrin repeats which are involved in dimer formation. It forms a component of the erythrocyte plasma membrane. Mutations in this gene result in a variety of hereditary red blood cell disorders, including elliptocytosis-2, pyropoikilocytosis, and spherocytosis, type 3. [provided by RefSeq, Aug 2017]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Elliptocytosis-2MIM #130600

PyropoikilocytosisMIM #266140

Spherocytosis, type 3MIM #270970

UniProtElliptocytosis 2

UniProtHereditary pyropoikilocytosis

UniProtSpherocytosis 3

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Elliptocytosis-2; Pyropoikilocytosis (+1); no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.49

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.000

Z-score 6.75

OE 0.39 (0.32–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-2.25Z-score

OE missense 1.18 (1.13–1.23)

1456 obs / 1233.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.39 (0.32–0.49)

0≤0.351.4

Missense OE?1.18 (1.13–1.23)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 57 / 144.6Missense obs/exp: 1456 / 1233.7Syn Z: -2.89

Background carrier burden — how many people carry a rare variant somewhere in SPTA1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 14

3,401 rare PASS variants

Rare truncating (LoF)

1 in 790

316 rare PASS variants

Rare synonymous (reference)

1 in 44

1,274 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SPTA1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 20	1 in 860
South Asian	~43k	1 in 14	1 in 560
Remaining (unassigned)	~30k	1 in 14	1 in 1,100
European (Finnish)	~27k	1 in 43	1 in 3,300
Admixed American	~22k	1 in 13	1 in 590
African / African American	~21k	1 in 13	1 in 560
East Asian	~20k	1 in 17	1 in 650
Ashkenazi Jewish	~13k	1 in 130	1 in 750
Middle Eastern	~2,884	1 in 15	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 49 of 52 coding exons well covered in gnomAD exomes; exons 1, 24, 49 marginal. Genomes: all 52.? see exons ↓