EMC7

Chr 15

ER membrane protein complex subunit 7

Also known as: C11orf3, C15orf24, HT022, ORF1-FL1

NCBI Gene: 56851 ENSG00000134153 UniProt: Q9NPA0 OMIM: 620631

Contributes to membrane insertase activity. Involved in protein insertion into ER membrane by stop-transfer membrane-anchor sequence and tail-anchored membrane protein insertion into ER membrane. Located in endoplasmic reticulum membrane. Part of EMC complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.43

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.43LOEUF

pLI 0.867

Z-score 2.79

OE 0.09 (0.03–0.43)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.39Z-score

OE missense 0.66 (0.56–0.79)

90 obs / 135.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.03–0.43)

0≤0.351.4

Missense OE?0.66 (0.56–0.79)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 1 / 11.0Missense obs/exp: 90 / 135.5Syn Z: 0.53

Background carrier burden — how many people carry a rare variant somewhere in EMC7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 770

235 rare PASS variants

Rare truncating (LoF)

1 in 30,000

13 rare PASS variants

Rare synonymous (reference)

1 in 620

111 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EMC7. 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 860	1 in 69,000
South Asian	~43k	1 in 250	≈ 1 in 22,000
Remaining (unassigned)	~30k	1 in 890	≈ 1 in 15,000
European (Finnish)	~27k	1 in 560	≈ 1 in 8,800
Admixed American	~22k	1 in 400	none seen
African / African American	~21k	1 in 390	≈ 1 in 21,000
East Asian	~20k	1 in 300	none seen
Ashkenazi Jewish	~13k	≈ 1 in 6,500	none seen
Middle Eastern	~2,884	1 in 580	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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓