ORC2

Chr 2

origin recognition complex subunit 2

Also known as: ORC2L

The ORC2 protein is a subunit of the origin recognition complex that is essential for initiating DNA replication in eukaryotic cells by binding to replication origins and recruiting additional replication factors. Mutations in ORC2 cause Meier-Gorlin syndrome, an autosomal recessive disorder characterized by primordial dwarfism, microtia, and absent or underdeveloped patellae. The gene is highly constrained against loss-of-function variants, reflecting its essential role in cellular replication.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.36
Clinical SummaryORC2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.84) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
32 unique Pathogenic / Likely Pathogenic· 63 VUS of 126 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.36LOEUF
pLI 0.844
Z-score 4.31
OE 0.18 (0.100.36)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.06Z-score
OE missense 0.82 (0.740.92)
235 obs / 285.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.18 (0.100.36)
00.351.4
Missense OE0.82 (0.740.92)
00.61.4
Synonymous OE0.81
01.21.6
LoF obs/exp: 6 / 32.5Missense obs/exp: 235 / 285.4Syn Z: 1.47
DN
0.3594th %ile
GOF
0.2099th %ile
LOF
0.64top 25%

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

LOFprediction above median · LOEUF 0.36

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

126 submitted variants in ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic1
VUS63
Likely Benign3
31
Pathogenic
1
Likely Pathogenic
63
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
1
0
1
VUS
0
59
4
0
63
Likely Benign
0
3
0
0
3
Benign
0
0
0
0
0
Total06236098

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

View in ClinVar →

Protein Context — Lollipop Plot

ORC2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗