NRN1L

Chr 16

neuritin 1 like

Also known as: MRCC2446, UNQ2446, cpg15-2

The protein is an extracellular ligand that enhances neurite growth and neuronal survival, functioning as a homodimer or heterodimer in both GPI-anchored membrane-bound and secreted forms. Based on the predicted gain-of-function mechanism and very low constraint scores (pLI 0.00009, LOEUF 1.78), mutations in this gene would likely cause disease through increased protein activity, though specific associated neurological disorders have not been established in the provided data.

Summary from RefSeq, Mechanism
Research Assistant →
0
Active trials
1
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.78
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryNRN1L
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.78LOEUF
pLI 0.000
Z-score -0.00
OE 1.00 (0.541.78)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.31Z-score
OE missense 1.08 (0.931.26)
121 obs / 111.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.00 (0.541.78)
00.351.4
Missense OE1.08 (0.931.26)
00.61.4
Synonymous OE1.35
01.21.6
LoF obs/exp: 6 / 6.0Missense obs/exp: 121 / 111.6Syn Z: -1.92
DN
0.7132th %ile
GOF
0.72top 25%
LOF
0.2774th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NRN1L · 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.

Search ClinicalTrials.gov →