GARNL3

Chr 9

GTPase activating Rap/RanGAP domain like 3

Also known as: bA356B19.1

NCBI Gene: 84253 ENSG00000136895 UniProt: Q5VVW2

The protein is predicted to function as a GTPase activator, regulating small GTPase-mediated signal transduction pathways. GARNL3 is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.50), suggesting that mutations in this gene would likely cause severe developmental disorders, though specific associated phenotypes have not yet been established in the literature. The inheritance pattern for GARNL3-related conditions remains to be determined.

ResearchSummary from RefSeq

Predicted to enable GTPase activator activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

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

0.50

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.50LOEUF

pLI 0.000

Z-score 4.62

OE 0.35 (0.24–0.50)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.02Z-score

OE missense 0.76 (0.70–0.82)

435 obs / 571.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.35 (0.24–0.50)

0≤0.351.4

Missense OE?0.76 (0.70–0.82)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 20 / 58.0Missense obs/exp: 435 / 571.0Syn Z: -0.51

Background carrier burden — how many people carry a rare variant somewhere in GARNL3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 54

1,115 rare PASS variants

Rare truncating (LoF)

1 in 1,600

152 rare PASS variants

Rare synonymous (reference)

1 in 100

497 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GARNL3. 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 69	1 in 2,000
South Asian	~43k	1 in 58	1 in 1,000
Remaining (unassigned)	~30k	1 in 56	1 in 3,800
European (Finnish)	~27k	1 in 150	1 in 3,200
Admixed American	~22k	1 in 62	1 in 1,000
African / African American	~21k	1 in 72	1 in 2,000
East Asian	~20k	1 in 56	1 in 2,700
Ashkenazi Jewish	~13k	1 in 270	1 in 740
Middle Eastern	~2,884	1 in 49	≈ 1 in 1,400

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): 21 of 28 coding exons well covered in gnomAD exomes; exons 3, 5, 10, 12, 16 and 2 more marginal. Genomes: all 28.? see exons ↓