EMC10

Chr 19AR

ER membrane protein complex subunit 10

Also known as: C19orf63, HSM1, HSS1, NEDDFAS

NCBI Gene: 284361 ENSG00000161671 UniProt: Q5UCC4 OMIM: 614545

EMC10 is part of the endoplasmic reticulum membrane protein complex that enables insertion of newly synthesized membrane proteins into ER membranes, particularly those with weakly hydrophobic transmembrane domains. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with dysmorphic facies and variable seizures. The gene shows very low constraint against loss-of-function variants (extremely low pLI), which is consistent with the recessive inheritance pattern observed clinically.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Contributes to membrane insertase activity. Involved in positive regulation of angiogenesis; positive regulation of endothelial cell proliferation; and protein insertion into ER membrane. Located in endoplasmic reticulum membrane and extracellular region. Part of EMC complex. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.601 OMIM phenotype

Clinical Summary— EMC10

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

14 unique Pathogenic / Likely Pathogenic· 49 VUS of 98 total submissions

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GeneReview available — EMC10

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.60LOEUF

pLI 0.000

Z-score -0.18

OE 1.05 (0.70–1.60)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.11Z-score

OE missense 0.98 (0.85–1.12)

152 obs / 155.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.05 (0.70–1.60)

0≤0.351.4

Missense OE?0.98 (0.85–1.12)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 15 / 14.3Missense obs/exp: 152 / 155.9Syn Z: -0.85

ClinVar Variant Classifications

98 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

Likely Pathogenic6

VUS49

Likely Benign19

Benign2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	8	0	0	0	8
Likely Pathogenic	6	0	0	0	6
VUS	0	48	0	1	49
Likely Benign	0	7	2	10	19
Benign	1	1	0	0	2
Total	15	56	2	11	84

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap EMC10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →