GRIK4

Chr 11

glutamate ionotropic receptor kainate type subunit 4

Also known as: EAA1, GRIK, GluK4, GluK4-2, KA1

NCBI Gene: 2900 ENSG00000149403 UniProt: Q16099

This gene encodes a protein that belongs to the glutamate-gated ionic channel family. Glutamate functions as the major excitatory neurotransmitter in the central nervous system through activation of ligand-gated ion channels and G protein-coupled membrane receptors. The protein encoded by this gene forms functional heteromeric kainate-preferring ionic channels with the subunits encoded by related gene family members. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

Research

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

0.41

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.111

Z-score 4.65

OE 0.25 (0.15–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.04Z-score

OE missense 0.76 (0.70–0.82)

436 obs / 573.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.25 (0.15–0.41)

0≤0.351.4

Missense OE?0.76 (0.70–0.82)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 11 / 44.5Missense obs/exp: 436 / 573.5Syn Z: -0.19

Background carrier burden — how many people carry a rare variant somewhere in GRIK4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 46

1,134 rare PASS variants

Rare truncating (LoF)

1 in 2,300

112 rare PASS variants

Rare synonymous (reference)

1 in 52

515 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GRIK4. 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 59	1 in 2,600
South Asian	~43k	1 in 57	1 in 920
Remaining (unassigned)	~30k	1 in 44	1 in 4,100
European (Finnish)	~27k	1 in 120	1 in 3,200
Admixed American	~22k	1 in 47	1 in 2,500
African / African American	~21k	1 in 45	1 in 4,100
East Asian	~20k	1 in 56	1 in 1,300
Ashkenazi Jewish	~13k	1 in 100	1 in 2,500
Middle Eastern	~2,884	1 in 49	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): 15 of 19 coding exons well covered in gnomAD exomes; exons 5, 8, 12, 20 marginal. Genomes: all 19.? see exons ↓