OBI1

Chr 13

ORC ubiquitin ligase 1

Also known as: C13orf7, RNF219

NCBI Gene: 79596 ENSG00000152193 UniProt: Q5W0B1

The protein is an E3 ubiquitin ligase essential for DNA replication origin activation during S phase, selecting which replication origins fire and catalyzing multi-mono-ubiquitination of chromatin-bound ORC3 and ORC5. Mutations cause autosomal recessive Meier-Gorlin syndrome, a primordial dwarfism disorder characterized by severe growth restriction, microcephaly, and absent or underdeveloped patellae and ears. The gene is not highly constrained against loss-of-function variants.

ResearchSummary from RefSeq, UniProt

Enables chromatin binding activity and ubiquitin-protein transferase activity. Involved in protein autoubiquitination; protein monoubiquitination; and regulation of DNA replication. Located in chromatin. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.87

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.87LOEUF

pLI 0.000

Z-score 2.11

OE 0.57 (0.39–0.87)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.15Z-score

OE missense 1.02 (0.94–1.11)

374 obs / 365.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.57 (0.39–0.87)

0≤0.351.4

Missense OE?1.02 (0.94–1.11)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 16 / 28.1Missense obs/exp: 374 / 365.9Syn Z: -0.28

Background carrier burden — how many people carry a rare variant somewhere in OBI1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 78

938 rare PASS variants

Rare truncating (LoF)

1 in 910

180 rare PASS variants

Rare synonymous (reference)

1 in 240

325 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for OBI1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 800
South Asian	~43k	1 in 63	1 in 1,400
Remaining (unassigned)	~30k	1 in 68	1 in 1,500
European (Finnish)	~27k	1 in 260	1 in 3,300
Admixed American	~22k	1 in 66	1 in 1,100
African / African American	~21k	1 in 71	1 in 580
East Asian	~20k	1 in 67	1 in 1,400
Ashkenazi Jewish	~13k	1 in 340	1 in 1,900
Middle Eastern	~2,884	1 in 96	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 6 coding exons well covered in gnomAD exomes; exons 3, 5 marginal. Genomes: all 6.? see exons ↓