ERMP1

Chr 9

endoplasmic reticulum metallopeptidase 1

Also known as: FXNA, KIAA1815, bA207C16.3

NCBI Gene: 79956 ENSG00000099219 UniProt: Q7Z2K6 OMIM: 611156

ERMP1 encodes a metalloexopeptidase involved in the endoplasmic reticulum unfolded protein response and cellular responses to oxidative stress. Mutations cause early infantile epileptic encephalopathy with developmental delay, intellectual disability, and seizures, inherited in an autosomal recessive pattern. The gene shows very low constraint against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable metal ion binding activity and metalloexopeptidase activity. Involved in cellular response to oxidative stress. Acts upstream of or within endoplasmic reticulum unfolded protein response. Located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

—

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.89

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.89LOEUF

pLI 0.000

Z-score 2.12

OE 0.63 (0.46–0.89)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.84Z-score

OE missense 1.11 (1.03–1.19)

519 obs / 467.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.63 (0.46–0.89)

0≤0.351.4

Missense OE?1.11 (1.03–1.19)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

LoF obs/exp: 25 / 39.4Missense obs/exp: 519 / 467.8Syn Z: -2.59

Background carrier burden — how many people carry a rare variant somewhere in ERMP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 53

1,440 rare PASS variants

Rare truncating (LoF)

1 in 470

202 rare PASS variants

Rare synonymous (reference)

1 in 110

543 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ERMP1. 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 70	1 in 420
South Asian	~43k	1 in 55	1 in 600
Remaining (unassigned)	~30k	1 in 44	1 in 610
European (Finnish)	~27k	1 in 130	1 in 1,900
Admixed American	~22k	1 in 59	1 in 770
African / African American	~21k	1 in 42	1 in 340
East Asian	~20k	1 in 47	1 in 800
Ashkenazi Jewish	~13k	1 in 180	1 in 1,300
Middle Eastern	~2,884	1 in 45	≈ 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.