GSG1L

Chr 16

GSG1 like

Also known as: PRO19651

NCBI Gene: 146395 ENSG00000169181 UniProt: Q6UXU4 OMIM: 617161

The protein functions as a component of the inner core of AMPA receptor complexes and modifies AMPA receptor gating, playing a role in synaptic transmission and plasticity. Mutations cause autosomal recessive developmental and epileptic encephalopathy with developmental delay, intellectual disability, and seizures. The gene shows moderate constraint against loss-of-function variants, supporting its important role in normal neurodevelopment.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in regulation of cell communication; regulation of postsynaptic neurotransmitter receptor internalization; and regulation of signaling. Predicted to act upstream of or within several processes, including regulation of AMPA receptor activity; regulation of short-term neuronal synaptic plasticity; and transmission of nerve impulse. Predicted to be located in asymmetric synapse and membrane. Predicted to be active in postsynaptic density membrane. [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

0.46

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.46LOEUF

pLI 0.768

Z-score 2.91

OE 0.15 (0.06–0.46)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.05Z-score

OE missense 0.76 (0.65–0.89)

114 obs / 150.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.15 (0.06–0.46)

0≤0.351.4

Missense OE?0.76 (0.65–0.89)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 2 / 13.6Missense obs/exp: 114 / 150.3Syn Z: 0.33

Background carrier burden — how many people carry a rare variant somewhere in GSG1L?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

486 rare PASS variants

Rare truncating (LoF)

1 in 2,900

59 rare PASS variants

Rare synonymous (reference)

1 in 160

236 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GSG1L. 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 200	1 in 6,700
South Asian	~43k	1 in 100	1 in 500
Remaining (unassigned)	~30k	1 in 100	1 in 3,900
European (Finnish)	~27k	1 in 290	1 in 2,200
Admixed American	~22k	1 in 130	1 in 3,200
African / African American	~21k	1 in 160	≈ 1 in 7,600
East Asian	~20k	1 in 250	≈ 1 in 4,500
Ashkenazi Jewish	~13k	1 in 270	1 in 2,200
Middle Eastern	~2,884	1 in 150	≈ 1 in 1,000

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.