EMC1

Chr 1AR

ER membrane protein complex subunit 1

Also known as: CAVIPMR, KIAA0090

NCBI Gene: 23065ENSG00000127463UniProt: Q8N766

This gene encodes a single-pass type I transmembrane protein, which is a subunit of the endoplasmic reticulum membrane protein complex (EMC). Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2012]

Primary Disease Associations & Inheritance

Cerebellar atrophy, visual impairment, and psychomotor retardationMIM #616875
AR
668
ClinVar variants
47
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— EMC1
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder with motor features · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
47 Pathogenic / Likely Pathogenic· 409 VUS of 668 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.01LOEUF
pLI 0.000
Z-score 1.49
OE 0.79 (0.62–1.01)
Tolerant

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.
1.35Z-score
OE missense 0.84 (0.78–0.91)
493 obs / 585.0 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.0.79 (0.62–1.01)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.78–0.91)
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.0.87
0≤1.21.6
LoF obs/exp: 46 / 58.3Missense obs/exp: 493 / 585.0Syn Z: 1.54

ClinVar Variant Classifications

668 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic22
VUS409
Likely Benign188
Benign20
Conflicting4
25
Pathogenic
22
Likely Pathogenic
409
VUS
188
Likely Benign
20
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
0
13
0
25
Likely Pathogenic
16
3
2
1
22
VUS
5
358
38
8
409
Likely Benign
0
2
84
102
188
Benign
0
2
12
6
20
Conflicting
—4
Total33365149117668

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

View in ClinVar →

Protein Context — Lollipop Plot

EMC1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

EMC1-related global developmental delay, hypotonia, scoliosis, and cerebellar atrophy

limited
ADDominant NegativeAltered Gene Product Structure
Dev. DisordersEye
G2P ↗
frameshift variantmissense variant

EMC1-related global developmental delay, hypotonia, scoliosis, and cerebellar atrophy

strong
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cerebellar atrophy, visual impairment, and psychomotor retardation

MIM #616875

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — EMC1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mechanisms Underlying Rare Inherited Pediatric Retinal Vascular Diseases: FEVR, Norrie Disease, Persistent Fetal Vascular Syndrome.
Le V et al.·Cells
2023Review
Monoallelic and Biallelic Variants in EMC1 Identified in Individuals with Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy.
Harel T et al.·Am J Hum Genet
2016
Compound heterozygous splicing variants expand the genotypic spectrum of EMC1-related disorders.
Bryen SJ et al.·Clin Genet
2023
Novel truncating and missense variants extending the spectrum of EMC1-related phenotypes, causing autism spectrum disorder, severe global development delay and visual impairment.
Cabet S et al.·Eur J Med Genet
2020Case report
A novel splice variant in EMC1 is associated with cerebellar atrophy, visual impairment, psychomotor retardation with epilepsy.
Geetha TS et al.·Mol Genet Genomic Med
2018Case report
Novel compound heterozygous variants in EMC1: Overlapping phenotypes of left ventricular noncompaction and long QT syndrome warranting in-depth exploration.
Dai X et al.·Prenat Diagn
2024Case report
Biallelic loss of EMC10 leads to mild to severe intellectual disability.
Kaiyrzhanov R et al.·Ann Clin Transl Neurol
2022
Prognostic Signature Development on the Basis of Macrophage Phagocytosis-Mediated Oxidative Phosphorylation in Bladder Cancer.
Qu G et al.·Oxid Med Cell Longev
2022
Endoplasmic reticulum membrane complex 1 facilitates BK polyomavirus genotype III/IV replication for nephropathy.
Fukae S et al.·Biochem Biophys Res Commun
2026
Lessons learned from additional research analyses of unsolved clinical exome cases.
Eldomery MK et al.·Genome Med
2017Cohort
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