CNTNAP1

Chr 17AR

contactin associated protein 1

Also known as: CASPR, CHN3, CNTNAP, NRXN4, P190

The protein is required for radial and longitudinal organization of myelinated axons and demarcates the paranodal region of the axo-glial junction, forming functional domains critical for saltatory conduction of nerve impulses. Mutations cause hypomyelinating neuropathy, congenital, 3 and lethal congenital contracture syndrome 7 through autosomal recessive inheritance. The pathogenicity results from disrupted signaling between axons and myelinating glial cells, impairing proper myelination and nerve conduction.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Hypomyelinating neuropathy, congenital, 3MIM #618186
AR
Lethal congenital contracture syndrome 7MIM #616286
AR
0
Active trials
6
Pubs (1 yr)
68
P/LP submissions
10%
P/LP missense
0.42
LOEUF
LOF
Mechanism· G2P
Clinical SummaryCNTNAP1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
52 unique Pathogenic / Likely Pathogenic· 240 VUS of 551 total submissions
📖
GeneReview available — CNTNAP1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

pubtator: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Missense constrained — critical functional residues
LoF Constraint
0.42LOEUF
pLI 0.000
Z-score 5.79
OE 0.30 (0.220.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.22Z-score
OE missense 0.70 (0.650.75)
630 obs / 902.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.30 (0.220.42)
00.351.4
Missense OE0.70 (0.650.75)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 24 / 79.9Missense obs/exp: 630 / 902.4Syn Z: 1.38
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCNTNAP1-related lethal congenital contracture syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6649th %ile
GOF
0.6346th %ile
LOF
0.2775th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

551 submitted variants in ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic18
VUS240
Likely Benign185
Benign51
Conflicting9
34
Pathogenic
18
Likely Pathogenic
240
VUS
185
Likely Benign
51
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
1
24
0
34
Likely Pathogenic
8
4
6
0
18
VUS
2
228
8
2
240
Likely Benign
0
5
74
106
185
Benign
0
1
41
9
51
Conflicting
9
Total19239153117537

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

View in ClinVar →

Protein Context — Lollipop Plot

CNTNAP1 · 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 →
Clinical Literature
Open Research Assistant →