RTN4RL1

Chr 17

reticulon 4 receptor like 1

Also known as: NGRH2, NgR3

NCBI Gene: 146760 ENSG00000185924 UniProt: Q86UN2

The protein functions as a cell surface receptor that regulates axon regeneration in the central nervous system, contributes to corpus callosum formation, and restricts dendritic spine and synapse formation during brain development. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and corpus callosum abnormalities. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

ResearchSummary from RefSeq, UniProt

Enables signaling receptor activity. Predicted to be involved in negative regulation of axon regeneration and positive regulation of synapse assembly. Located in cell surface and 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

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P/LP missense

0.30

LOEUF· LoF intol.

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Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.960

Z-score 2.94

OE 0.00 (0.00–0.30)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.47Z-score

OE missense 0.75 (0.67–0.84)

212 obs / 281.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.30)

0≤0.351.4

Missense OE?0.75 (0.67–0.84)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 0 / 10.1Missense obs/exp: 212 / 281.4Syn Z: -0.51

Background carrier burden — how many people carry a rare variant somewhere in RTN4RL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 75

531 rare PASS variants

Rare truncating (LoF)

1 in 9,100

31 rare PASS variants

Rare synonymous (reference)

1 in 94

319 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RTN4RL1. 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 140	1 in 8,600
South Asian	~43k	1 in 86	≈ 1 in 20,000
Remaining (unassigned)	~30k	1 in 79	≈ 1 in 30,000
European (Finnish)	~27k	1 in 390	≈ 1 in 8,100
Admixed American	~22k	1 in 77	≈ 1 in 7,600
African / African American	~21k	1 in 78	≈ 1 in 21,000
East Asian	~20k	1 in 120	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 380	≈ 1 in 6,300
Middle Eastern	~2,884	1 in 72	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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓