ORC4

Chr 2AR

origin recognition complex subunit 4

Also known as: ORC4L, ORC4P

The origin recognition complex (ORC) is a highly conserved six subunit protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins. This gene encodes a subunit of the ORC complex. Several alternatively spliced transcript variants, some of which encode the same protein, have been reported for this gene. [provided by RefSeq, Oct 2010]

OMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 1.131 OMIM phenotype
Clinical SummaryORC4
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Gene-Disease Validity (ClinGen)
Meier-Gorlin syndrome 2 · ARModerate

Moderate evidence — consider for supplementary testing

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.13LOEUF
pLI 0.000
Z-score 1.02
OE 0.79 (0.561.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.20Z-score
OE missense 1.04 (0.931.16)
231 obs / 222.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.79 (0.561.13)
00.351.4
Missense OE?1.04 (0.931.16)
00.61.4
Synonymous OE?0.85
01.21.6
LoF obs/exp: 22 / 27.8Missense obs/exp: 231 / 222.5Syn Z: 1.00
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveORC4-related Meier-Gorlin syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6648th %ile
GOF
0.3491th %ile
LOF
0.4038th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ORC4 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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