EMC6

Chr 17

ER membrane protein complex subunit 6

Also known as: RAB5IFL, TMEM93

NCBI Gene: 83460ENSG00000127774UniProt: Q9BV81

Contributes to membrane insertase activity. Involved in autophagosome assembly; 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 and omegasome membrane. Part of EMC complex. [provided by Alliance of Genome Resources, Jul 2025]

67
ClinVar variants
32
Pathogenic / LP
0.52
pLI score
0
Active trials
Clinical Summary— EMC6
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.52) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
32 Pathogenic / Likely Pathogenic· 31 VUS of 67 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.29LOEUF
pLI 0.523
Z-score 1.36
OE 0.00 (0.00–1.29)
Moderately constrained

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.15Z-score
OE missense 0.60 (0.46–0.78)
38 obs / 63.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–1.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.60 (0.46–0.78)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.43
0≤1.21.6
LoF obs/exp: 0 / 2.1Missense obs/exp: 38 / 63.8Syn Z: -1.95

ClinVar Variant Classifications

67 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic1
VUS31
Likely Benign3
Conflicting1
31
Pathogenic
1
Likely Pathogenic
31
VUS
3
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
1
0
1
VUS
0
12
19
0
31
Likely Benign
0
0
3
0
3
Benign
0
0
0
0
0
Conflicting
—1
Total01254067

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

EMC6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools