RTN4RL1

Chr 17

reticulon 4 receptor like 1

Also known as: NGRH2, NgR3

NCBI Gene: 146760 ENSG00000185924 UniProt: Q86UN2 OMIM: 610461

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables signaling receptor activity. Predicted to be involved in negative regulation of axon regeneration. Located in cell surface and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.30

Clinical Summary— RTN4RL1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

29 VUS of 36 total submissions

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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

ClinVar Variant Classifications

36 submitted variants in ClinVar

ClinVar

Classification Summary

VUS29

Likely Benign2

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	29	0	29
Likely Benign	0	2	2
Benign	2	2	4
Total	31	4	35

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

65 pathogenic / likely-pathogenic (of 82) ClinVar copy-number / structural variants overlap RTN4RL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →