UBXN1

Chr 11

UBX domain protein 1

Also known as: 2B28, SAKS1, UBXD10

NCBI Gene: 51035 ENSG00000162191 UniProt: Q04323 OMIM: 616378

UBXN1 encodes a ubiquitin-binding protein that regulates innate immune response by modulating RIG-I-like receptor and NF-kappa-B signaling pathways, and participates in endoplasmic reticulum protein quality control. Mutations cause autosomal recessive intellectual disability with seizures and dysmorphic features, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.445), suggesting intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

Enables several functions, including enzyme binding activity; polyubiquitin modification-dependent protein binding activity; and proteasome regulatory particle binding activity. Involved in negative regulation of protein metabolic process. Located in cytosol and endoplasmic reticulum. Part of VCP-NPL4-UFD1 AAA ATPase complex. [provided by Alliance of Genome Resources, Jun 2026]

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

0.45

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.728

Z-score 3.20

OE 0.17 (0.08–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.84Z-score

OE missense 0.83 (0.73–0.95)

160 obs / 192.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.17 (0.08–0.45)

0≤0.351.4

Missense OE?0.83 (0.73–0.95)

0≤0.61.4

Synonymous OE?1.19

0≤1.21.6

LoF obs/exp: 3 / 17.4Missense obs/exp: 160 / 192.7Syn Z: -1.25

Background carrier burden — how many people carry a rare variant somewhere in UBXN1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

450 rare PASS variants

Rare truncating (LoF)

1 in 4,000

73 rare PASS variants

Rare synonymous (reference)

1 in 460

190 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UBXN1. 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 350	1 in 4,000
South Asian	~43k	1 in 100	1 in 3,100
Remaining (unassigned)	~30k	1 in 170	1 in 4,300
European (Finnish)	~27k	1 in 880	1 in 2,900
Admixed American	~22k	1 in 130	≈ 1 in 4,500
African / African American	~21k	1 in 230	≈ 1 in 21,000
East Asian	~20k	1 in 170	1 in 4,000
Ashkenazi Jewish	~13k	1 in 770	none seen
Middle Eastern	~2,884	1 in 170	≈ 1 in 660

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): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓