CNTN5

Chr 11

contactin 5

Also known as: HNB-2s, NB-2

NCBI Gene: 53942ENSG00000149972UniProt: O94779

The protein encoded by this gene is a member of the immunoglobulin superfamily, and contactin family, which mediate cell surface interactions during nervous system development. This protein is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

256
ClinVar variants
16
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CNTN5
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 205 VUS of 256 total submissions

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.
0.48LOEUF
pLI 0.000
Z-score 4.62
OE 0.33 (0.23–0.48)
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.
-0.34Z-score
OE missense 1.04 (0.97–1.11)
599 obs / 576.3 exp
Tolerant

Tolerant to missense variation

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.0.33 (0.23–0.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (0.97–1.11)
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.1.16
0≤1.21.6
LoF obs/exp: 18 / 55.0Missense obs/exp: 599 / 576.3Syn Z: -1.77

ClinVar Variant Classifications

256 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic3
VUS205
Likely Benign18
Benign15
Conflicting2
13
Pathogenic
3
Likely Pathogenic
205
VUS
18
Likely Benign
15
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
3
0
3
VUS
1
168
36
0
205
Likely Benign
0
6
4
8
18
Benign
0
7
3
5
15
Conflicting
—2
Total11815913256

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

View in ClinVar →

Protein Context — Lollipop Plot

CNTN5 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
CONTACTIN 5; CNTN5
MIM #607219 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.
Monies D et al.·Hum Genet
2017
Loss of primary cilia and dopaminergic neuroprotection in pathogenic LRRK2-driven and idiopathic Parkinson's disease.
Khan SS et al.·Proc Natl Acad Sci U S A
2024
Association Analysis of Rare CNTN5 Variants With Autism Spectrum Disorder in a Japanese Population.
Hadi AF et al.·Neuropsychopharmacol Rep
2025
Genetic Alterations in a Large Population of Italian Patients Affected by Neurodevelopmental Disorders.
Ranieri A et al.·Genes (Basel)
2024Cohort
CNTN5(-)(/+)or EHMT2(-)(/+)human iPSC-derived neurons from individuals with autism develop hyperactive neuronal networks.
Deneault E et al.·Elife
2019
Unraveling genetic risk contributions to nonverbal status in autism spectrum disorder probands.
Liu H et al.·Behav Brain Funct
2025
CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders.
Mercati O et al.·Mol Psychiatry
2017
Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis: A Meta-Analysis of Two Large Cohorts.
Sánchez-Maldonado JM et al.·Front Immunol
2021Meta-analysis
Contactin proteins in cerebrospinal fluid show different alterations in dementias.
Muqaku B et al.·J Neurol
2024
Genetic Variants Associated with Suspected Neonatal Hypoxic Ischaemic Encephalopathy: A Study in a South African Context.
Foden CJ et al.·Int J Mol Sci
2025
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