EME2

Chr 16

essential meiotic structure-specific endonuclease subunit 2

Also known as: SLX2B, gs125

NCBI Gene: 197342 ENSG00000197774 UniProt: A4GXA9 OMIM: 610886

EME2 encodes the non-catalytic subunit of the MUS81-EME2 endonuclease complex that cleaves DNA structures during replication fork processing and genome maintenance. Mutations cause a rare autosomal recessive disorder characterized by severe intellectual disability, microcephaly, growth retardation, and distinctive facial features. This gene shows low constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, UniProt

EME2 forms a heterodimer with MUS81 (MIM 606591) that functions as an XPF (MIM 278760)-type flap/fork endonuclease in DNA repair (Ciccia et al., 2007 [PubMed 17289582]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 1.94

Clinical Summary— EME2

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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

3 unique Pathogenic / Likely Pathogenic· 118 VUS of 185 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.94LOEUF

pLI 0.000

Z-score -2.35

OE 1.61 (1.17–1.94)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.78Z-score

OE missense 1.33 (1.21–1.46)

309 obs / 232.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.61 (1.17–1.94)

0≤0.351.4

Missense OE?1.33 (1.21–1.46)

0≤0.61.4

Synonymous OE?1.37

0≤1.21.6

LoF obs/exp: 28 / 17.4Missense obs/exp: 309 / 232.7Syn Z: -2.90

ClinVar Variant Classifications

185 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic2

VUS118

Likely Benign28

Benign10

Pathogenic

Likely Pathogenic

118

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	1	0	0	1
Likely Pathogenic	1	1	0	2
VUS	0	118	0	118
Likely Benign	0	6	22	28
Benign	1	5	4	10
Total	3	130	26	159

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

View in ClinVar →

41 pathogenic / likely-pathogenic (of 58) ClinVar copy-number / structural variants overlap EME2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →