CNTNAP3B

Chr 9

contactin associated protein family member 3B

NCBI Gene: 728577 ENSG00000154529 UniProt: Q96NU0

The protein is predicted to function in cell adhesion and is located in cellular membranes. Mutations in this gene cause neurodevelopmental disorders with intellectual disability, though the clinical phenotype is not well-characterized given limited reported cases. The gene shows very low constraint against loss-of-function variants (high LOEUF score), suggesting it may tolerate some degree of functional disruption.

ResearchSummary from RefSeq

Predicted to be involved in nervous system development and signal transduction. Predicted to be located in membrane. Predicted to be active in plasma membrane and synapse. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.67

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.67LOEUF

pLI 0.000

Z-score -1.39

OE 1.27 (0.98–1.67)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.48Z-score

OE missense 1.40 (1.29–1.52)

423 obs / 301.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.27 (0.98–1.67)

0≤0.351.4

Missense OE?1.40 (1.29–1.52)

0≤0.61.4

Synonymous OE?1.28

0≤1.21.6

LoF obs/exp: 38 / 29.8Missense obs/exp: 423 / 301.8Syn Z: -2.49

Background carrier burden — how many people carry a rare variant somewhere in CNTNAP3B?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 27

561 rare PASS variants

Rare truncating (LoF)

1 in 96

104 rare PASS variants

Rare synonymous (reference)

1 in 59

217 rare PASS variants

Rare missense and truncating variants are carried at similar rates in CNTNAP3B; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 42	1 in 360
South Asian	~43k	1 in 31	1 in 190
Remaining (unassigned)	~30k	1 in 21	1 in 120
European (Finnish)	~27k	1 in 66	1 in 1,400
Admixed American	~22k	1 in 25	1 in 120
African / African American	~21k	1 in 27	1 in 130
East Asian	~20k	1 in 38	1 in 150
Ashkenazi Jewish	~13k	1 in 210	1 in 1,700
Middle Eastern	~2,880	1 in 72	≈ 1 in 700

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 8 of 24 coding exons well covered in gnomAD exomes; exons 4, 10, 19, 20, 21 and 3 more poorly covered; exons 2, 5, 6, 7, 8 and 3 more marginal. Genomes: 5 of 24 (exons 1, 2, 3, 4, 5 and 14 more below).? see exons ↓