NRN1

Chr 6

neuritin 1

Also known as: NRN, dJ380B8.2

NCBI Gene: 51299 ENSG00000124785 UniProt: Q9NPD7 OMIM: 607409

The protein promotes neurite outgrowth and branching of neuritic processes in hippocampal and cortical neurons, functioning as a GPI-anchored protein that responds to neural activity and neurotrophins. The gene is highly constrained against loss-of-function variants (pLI = 0.86, LOEUF = 0.46), suggesting that mutations would likely cause significant neurological phenotypes, though specific associated diseases have not yet been definitively established in humans. Further research is needed to characterize the clinical manifestations of NRN1-related disorders.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the neuritin family, and is expressed in postmitotic-differentiating neurons of the developmental nervous system and neuronal structures associated with plasticity in the adult. The expression of this gene can be induced by neural activity and neurotrophins. The encoded protein contains a consensus cleavage signal found in glycosylphoshatidylinositol (GPI)-anchored proteins. The encoded protein promotes neurite outgrowth and arborization, suggesting its role in promoting neuritogenesis. Overexpression of the encoded protein may be associated with astrocytoma progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

OMIM ResearchGenerating clinical summary…

LOEUF 0.46

Clinical Summary— NRN1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.86) — some intolerance to loss-of-function variants.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 12 VUS of 21 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.46LOEUF

pLI 0.860

Z-score 2.35

OE 0.00 (0.00–0.46)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.14Z-score

OE missense 0.64 (0.52–0.81)

53 obs / 82.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.46)

0≤0.351.4

Missense OE?0.64 (0.52–0.81)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 0 / 6.4Missense obs/exp: 53 / 82.2Syn Z: -0.47

ClinVar Variant Classifications

21 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS12

Likely Benign2

Benign1

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	1	1
Likely Pathogenic	0	0	0
VUS	11	1	12
Likely Benign	2	0	2
Benign	1	0	1
Total	14	2	16

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

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37 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap NRN1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →