ARMC8

Chr 3

armadillo repeat containing 8

Also known as: GID5, HSPC056, S863-2, VID28

NCBI Gene: 25852 ENSG00000114098 UniProt: Q8IUR7 OMIM: 618521

Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Located in cytosol and nucleoplasm. Part of ubiquitin ligase complex. [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

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 5.81

OE 0.07 (0.03–0.17)

Highly constrained

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

Missense Constraint?

2.88Z-score

OE missense 0.57 (0.51–0.64)

199 obs / 350.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.07 (0.03–0.17)

0≤0.351.4

Missense OE?0.57 (0.51–0.64)

0≤0.61.4

Synonymous OE?0.76

0≤1.21.6

LoF obs/exp: 3 / 45.1Missense obs/exp: 199 / 350.8Syn Z: 2.09

Background carrier burden — how many people carry a rare variant somewhere in ARMC8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

650 rare PASS variants

Rare truncating (LoF)

1 in 5,300

57 rare PASS variants

Rare synonymous (reference)

1 in 310

282 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ARMC8. 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 210	1 in 3,700
South Asian	~43k	1 in 160	1 in 5,300
Remaining (unassigned)	~30k	1 in 220	1 in 6,000
European (Finnish)	~27k	1 in 380	≈ 1 in 27,000
Admixed American	~22k	1 in 150	≈ 1 in 5,500
African / African American	~21k	1 in 120	≈ 1 in 5,600
East Asian	~20k	1 in 220	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 370	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 170	none seen

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): 19 of 22 coding exons well covered in gnomAD exomes; exons 6, 10, 15 marginal. Genomes: 21 of 22 (exon 6 below).? see exons ↓