EPB42

Chr 15

erythrocyte membrane protein band 4.2

Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane

Research

Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpherocytosis 5

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.77

LOEUF

Mechanism· predicted

Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.77LOEUF

pLI 0.000

Z-score 2.63

OE 0.53 (0.37–0.77)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.94Z-score

OE missense 0.87 (0.79–0.95)

348 obs / 400.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.53 (0.37–0.77)

0≤0.351.4

Missense OE?0.87 (0.79–0.95)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 19 / 36.1Missense obs/exp: 348 / 400.9Syn Z: 0.67

Background carrier burden — how many people carry a rare variant somewhere in EPB42?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 63

866 rare PASS variants

Rare truncating (LoF)

1 in 520

127 rare PASS variants

Rare synonymous (reference)

1 in 110

355 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EPB42. 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 72	1 in 850
South Asian	~43k	1 in 70	1 in 1,000
Remaining (unassigned)	~30k	1 in 46	1 in 400
European (Finnish)	~27k	1 in 190	1 in 340
Admixed American	~22k	1 in 57	1 in 720
African / African American	~21k	1 in 48	1 in 1,000
East Asian	~20k	1 in 43	1 in 350
Ashkenazi Jewish	~13k	1 in 380	1 in 2,000
Middle Eastern	~2,884	1 in 71	none seen

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): All 13 coding exons well covered in gnomAD exomes and genomes.? see exons ↓