ARIH1

Chr 15

ariadne RBR E3 ubiquitin protein ligase 1

Also known as: ARI, HARI, HHARI, UBCH7BP

NCBI Gene: 25820 ENSG00000166233 UniProt: Q9Y4X5 OMIM: 605624

Enables enzyme binding activity; ubiquitin-protein transferase activity; and zinc ion binding activity. Involved in protein ubiquitination. Located in several cellular components, including Lewy body; cullin-RING ubiquitin ligase complex; and nuclear body. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.17

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 5.40

OE 0.05 (0.02–0.17)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

4.59Z-score

OE missense 0.25 (0.21–0.30)

74 obs / 296.5 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.05 (0.02–0.17)

0≤0.351.4

Missense OE?0.25 (0.21–0.30)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 2 / 37.9Missense obs/exp: 74 / 296.5Syn Z: 0.31

Background carrier burden — how many people carry a rare variant somewhere in ARIH1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 410

337 rare PASS variants

Rare truncating (LoF)

1 in 52,000

11 rare PASS variants

Rare synonymous (reference)

1 in 150

256 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ARIH1. 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 480	1 in 79,000
South Asian	~43k	1 in 780	none seen
Remaining (unassigned)	~30k	1 in 370	none seen
European (Finnish)	~27k	1 in 930	≈ 1 in 13,000
Admixed American	~22k	1 in 610	none seen
African / African American	~21k	1 in 470	none seen
East Asian	~20k	1 in 660	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 2,600	none seen
Middle Eastern	~2,884	1 in 280	≈ 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): 8 of 14 coding exons well covered in gnomAD exomes; exons 1, 4, 5, 6, 8, 11 marginal. Genomes: all 14.? see exons ↓