EMC6

Chr 17

ER membrane protein complex subunit 6

Also known as: RAB5IFL, TMEM93

NCBI Gene: 83460 ENSG00000127774 UniProt: Q9BV81 OMIM: 620261

EMC6 encodes a component of the endoplasmic reticulum membrane protein complex that facilitates insertion of newly synthesized membrane proteins into ER membranes, particularly those with weakly hydrophobic transmembrane domains. Mutations cause autosomal recessive neurodevelopmental disorder with epilepsy and microcephaly, with affected children typically presenting in infancy with developmental delays, seizures, and growth abnormalities. The gene shows intermediate constraint against loss-of-function mutations (pLI 0.52, LOEUF 1.29), consistent with recessive inheritance.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOEUF 1.29

Clinical Summary— EMC6

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.52) — some intolerance to loss-of-function variants.

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ClinVar Variants

12 VUS of 13 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

1.15Z-score

OE missense 0.60 (0.46–0.78)

38 obs / 63.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.29)

0≤0.351.4

Missense OE?0.60 (0.46–0.78)

0≤0.61.4

Synonymous OE?1.43

0≤1.21.6

LoF obs/exp: 0 / 2.1Missense obs/exp: 38 / 63.8Syn Z: -1.95

ClinVar Variant Classifications

13 submitted variants in ClinVar

ClinVar

Classification Summary

VUS12

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	12	12
Likely Benign	0	0
Benign	0	0
Total	12	12

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

View in ClinVar →

33 pathogenic / likely-pathogenic (of 58) ClinVar copy-number / structural variants overlap EMC6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →