ORC4

Chr 2AR

origin recognition complex subunit 4

Also known as: ORC4L, ORC4P

ORC4 encodes a component of the origin recognition complex that binds to origins of DNA replication in an ATP-dependent manner and is required for assembly of the pre-replication complex necessary to initiate DNA replication. Biallelic mutations cause Meier-Gorlin syndrome 2, characterized by microcephaly, short stature, and small ears, with an autosomal recessive inheritance pattern. The gene shows minimal constraint against loss-of-function variants (pLI near zero), consistent with the recessive disease mechanism.

OMIMResearchSummary from RefSeq, OMIM, UniProt
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 OE0.79 (0.561.13)
00.351.4
Missense OE1.04 (0.931.16)
00.61.4
Synonymous OE0.85
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

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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