RTN4R

Chr 22AD

reticulon 4 receptor

Also known as: NGR, NOGOR, NgR1

NCBI Gene: 65078 ENSG00000040608 UniProt: Q9BZR6 OMIM: 605566

This gene encodes a receptor for multiple myelin-associated proteins (reticulon 4, oligodendrocyte myelin glycoprotein, and myelin-associated glycoprotein) that mediates axonal growth inhibition and regulates axon regeneration, neuronal plasticity, and synaptic formation in the central nervous system. Mutations cause autosomal dominant susceptibility to schizophrenia. The gene is highly constrained against loss-of-function variants (pLI 0.96, LOEUF 0.3), suggesting that complete loss of function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the receptor for reticulon 4, oligodendrocyte myelin glycoprotein and myelin-associated glycoprotein. This receptor mediates axonal growth inhibition and may play a role in regulating axonal regeneration and plasticity in the adult central nervous system. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Schizophrenia, susceptibility to}MIM #181500

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

0.30

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.959

Z-score 2.93

OE 0.00 (0.00–0.30)

Highly constrained

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

Missense Constraint?

1.13Z-score

OE missense 0.82 (0.74–0.91)

265 obs / 322.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.30)

0≤0.351.4

Missense OE?0.82 (0.74–0.91)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 0 / 10.0Missense obs/exp: 265 / 322.2Syn Z: 0.13

Background carrier burden — how many people carry a rare variant somewhere in RTN4R?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 68

699 rare PASS variants

Rare truncating (LoF)

1 in 850

37 rare PASS variants

Rare synonymous (reference)

1 in 80

362 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RTN4R. 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 94	1 in 880
South Asian	~43k	1 in 48	1 in 450
Remaining (unassigned)	~30k	1 in 54	1 in 760
European (Finnish)	~27k	1 in 380	1 in 2,100
Admixed American	~22k	1 in 61	1 in 3,900
African / African American	~21k	1 in 42	1 in 660
East Asian	~20k	1 in 81	1 in 2,100
Ashkenazi Jewish	~13k	1 in 490	none seen
Middle Eastern	~2,884	1 in 58	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): 1 of 2 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 2.? see exons ↓