EMC8

Chr 16

ER membrane protein complex subunit 8

Also known as: C16orf2, C16orf4, COX4NB, FAM158B, NOC4

NCBI Gene: 10328 ENSG00000131148 UniProt: O43402

EMC8 encodes a component of the endoplasmic reticulum membrane protein complex that mediates insertion of newly synthesized membrane proteins into ER membranes, particularly those with weakly hydrophobic transmembrane domains. Mutations cause autosomal recessive intellectual disability and developmental delay. This gene is highly constrained against loss-of-function variants, indicating intolerance to protein loss.

ResearchSummary from RefSeq, UniProt

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 Golgi apparatus and endoplasmic reticulum. Part of EMC complex. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.45

Clinical Summary— EMC8

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.

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ClinVar Variants

23 VUS of 31 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.852

Z-score 2.74

OE 0.09 (0.03–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.62Z-score

OE missense 0.85 (0.73–0.99)

113 obs / 133.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.03–0.45)

0≤0.351.4

Missense OE?0.85 (0.73–0.99)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 1 / 10.7Missense obs/exp: 113 / 133.2Syn Z: -1.26

This gene — mechanism propensity

0.3296th %ile

GOF

0.2895th %ile

LOF

0.66top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.45

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

31 submitted variants in ClinVar

ClinVar

Classification Summary

VUS23

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	23	23
Likely Benign	0	0
Benign	0	0
Total	23	23

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

View in ClinVar →

44 pathogenic / likely-pathogenic (of 59) ClinVar copy-number / structural variants overlap EMC8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →