GAREM1

Chr 18

GRB2 associated regulator of MAPK1 subtype 1

Also known as: C18orf11, FAM59A, GAREM, Gm944

This protein functions as an adapter in epidermal growth factor receptor signaling and promotes activation of the MAPK/ERK pathway to regulate cell proliferation. Mutations cause neurodevelopmental disorder with seizures and brain atrophy, inherited in an autosomal recessive pattern. The gene shows high constraint against loss-of-function variants (LOEUF 0.44), indicating intolerance to protein disruption.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.44
LOEUF
Mechanism
Clinical SummaryGAREM1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.44LOEUF
pLI 0.199
Z-score 4.04
OE 0.24 (0.140.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.04Z-score
OE missense 0.87 (0.800.94)
429 obs / 493.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.24 (0.140.44)
00.351.4
Missense OE0.87 (0.800.94)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 8 / 33.1Missense obs/exp: 429 / 493.9Syn Z: -0.08

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GAREM1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC