ARGLU1

Chr 13

arginine and glutamate rich 1

NCBI Gene: 55082 ENSG00000134884 UniProt: Q9NWB6 OMIM: 614046

This protein functions as a dual regulator of gene expression, serving as a transcriptional coactivator for nuclear receptors and directly modulating alternative splicing of pre-mRNAs through binding to spliceosome components. Mutations cause neurodevelopmental disorders affecting the central nervous system, heart development, and neuronal function. The gene shows autosomal dominant inheritance and is highly constrained against loss-of-function variants, indicating that even single functional copies are critical for normal development.

OMIM ResearchSummary from RefSeq, UniProt

Enables pre-mRNA binding activity and transcription coactivator activity. Involved in regulation of alternative mRNA splicing, via spliceosome. Located in nuclear speck. [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

0.39

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.39LOEUF

pLI 0.862

Z-score 3.48

OE 0.15 (0.07–0.39)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.48Z-score

OE missense 0.44 (0.36–0.54)

70 obs / 157.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.15 (0.07–0.39)

0≤0.351.4

Missense OE?0.44 (0.36–0.54)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 3 / 19.7Missense obs/exp: 70 / 157.6Syn Z: -0.80

Background carrier burden — how many people carry a rare variant somewhere in ARGLU1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 410

228 rare PASS variants

Rare truncating (LoF)

1 in 28,000

16 rare PASS variants

Rare synonymous (reference)

1 in 410

179 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ARGLU1. 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 600	1 in 43,000
South Asian	~43k	1 in 1,400	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 230	≈ 1 in 30,000
European (Finnish)	~27k	1 in 970	none seen
Admixed American	~22k	1 in 290	none seen
African / African American	~21k	1 in 530	none seen
East Asian	~20k	1 in 240	none seen
Ashkenazi Jewish	~13k	1 in 770	1 in 1,500
Middle Eastern	~2,884	1 in 410	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): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓