NRCAM

Chr 7

neuronal cell adhesion molecule

Also known as: NEDNMS

NCBI Gene: 4897ENSG00000091129UniProt: Q92823

Cell adhesion molecules (CAMs) are members of the immunoglobulin superfamily. This gene encodes a neuronal cell adhesion molecule with multiple immunoglobulin-like C2-type domains and fibronectin type-III domains. This ankyrin-binding protein is involved in neuron-neuron adhesion and promotes directional signaling during axonal cone growth. This gene is also expressed in non-neural tissues and may play a general role in cell-cell communication via signaling from its intracellular domain to the actin cytoskeleton during directional cell migration. Allelic variants of this gene have been associated with autism and addiction vulnerability. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with neuromuscular and skeletal abnormalities
260
ClinVar variants
34
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— NRCAM
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
34 Pathogenic / Likely Pathogenic· 198 VUS of 260 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.38LOEUF
pLI 0.015
Z-score 5.74
OE 0.26 (0.18–0.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.91Z-score
OE missense 0.80 (0.74–0.85)
566 obs / 709.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.26 (0.18–0.38)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.74–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.89
0≤1.21.6
LoF obs/exp: 18 / 69.8Missense obs/exp: 566 / 709.5Syn Z: 1.35

ClinVar Variant Classifications

260 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic4
VUS198
Likely Benign19
Benign8
Conflicting1
30
Pathogenic
4
Likely Pathogenic
198
VUS
19
Likely Benign
8
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
4
23
0
30
Likely Pathogenic
2
0
2
0
4
VUS
1
189
8
0
198
Likely Benign
0
7
4
8
19
Benign
0
2
3
3
8
Conflicting
—1
Total62024011260

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

View in ClinVar →

Protein Context — Lollipop Plot

NRCAM · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

NRCAM-related neurodevelopmental disorder with dysmorphic features, hypotonia, and spasticity

moderate
ARUndeterminedAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
NRCAM variant defined by microexon skipping is a targetable cell surface proteoform in high-grade gliomas.
Sehgal P et al.·Cell Rep
2025
NRCAM acts as a prognostic biomarker and promotes the tumor progression in gastric cancer via EMT pathway.
Bai C et al.·Tissue Cell
2022
Exome sequencing findings in children with annular pancreas.
Pitsava G et al.·Mol Genet Genomic Med
2023
NrCAM is a marker for substrate-selective activation of ADAM10 in Alzheimer's disease.
Brummer T et al.·EMBO Mol Med
2019
Bi-allelic loss of function variant in the NRCAM gene is associated with motor-predominant axonal polyneuropathy; the second report.
Elahi Z et al.·Mol Genet Genomic Med
2023Case report
Perinatal mood and anxiety disorders: biomarker discovery using plasma proteomics.
Accortt E et al.·Am J Obstet Gynecol
2023
Investigating the diagnostic significance of serum NRCAM in small cell lung cancer.
Chen Y et al.·Clin Chim Acta
2026
Alternative splicing of human NrCAM in neural and nonneural tissues.
Wang B et al.·Mol Cell Neurosci
1998
Serum molecular biomarkers in neuromyelitis optica and multiple sclerosis.
Fu CC et al.·Mult Scler Relat Disord
2022
Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes.
Hutcheson HB et al.·BMC Med Genet
2004
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools