CNTNAP3

Chr 9

contactin associated protein family member 3

Also known as: CASPR3, CNTNAP3A

NCBI Gene: 79937 ENSG00000106714 UniProt: Q9BZ76

The encoded protein is a cell-recognition molecule that mediates neuron-glial interactions within the nervous system. Mutations cause autosomal recessive neurodevelopmental disorders including developmental and epileptic encephalopathy, intellectual disability, and cortical visual impairment with onset in infancy or early childhood. This gene shows minimal constraint against loss-of-function variants.

ResearchSummary from RefSeq

The protein encoded by this gene belongs to the NCP family of cell-recognition molecules. This family represents a distinct subgroup of the neurexins. NCP proteins mediate neuron-glial interactions in vertebrates and glial-glial contact in invertebrates. The protein encoded by this gene may play a role in cell recognition within the nervous system. Alternatively spliced transcript variants encoding different isoforms have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.77

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.77LOEUF

pLI 0.000

Z-score 2.82

OE 0.55 (0.40–0.77)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.15Z-score

OE missense 0.98 (0.91–1.06)

518 obs / 527.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.55 (0.40–0.77)

0≤0.351.4

Missense OE?0.98 (0.91–1.06)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 25 / 45.5Missense obs/exp: 518 / 527.4Syn Z: -1.57

Background carrier burden — how many people carry a rare variant somewhere in CNTNAP3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 46

716 rare PASS variants

Rare truncating (LoF)

1 in 430

95 rare PASS variants

Rare synonymous (reference)

1 in 54

300 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CNTNAP3. 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 66	1 in 620
South Asian	~43k	1 in 47	1 in 790
Remaining (unassigned)	~30k	1 in 41	1 in 280
European (Finnish)	~27k	1 in 240	1 in 740
Admixed American	~22k	1 in 40	1 in 530
African / African American	~21k	1 in 42	1 in 590
East Asian	~20k	1 in 48	1 in 250
Ashkenazi Jewish	~13k	1 in 290	≈ 1 in 13,000
Middle Eastern	~2,881	1 in 68	none seen

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): 14 of 24 coding exons well covered in gnomAD exomes; exons 1, 2, 3, 4, 5 and 4 more poorly covered; exon 17 marginal. Genomes: 12 of 24 (exons 1, 2, 3, 4, 5 and 7 more below).? see exons ↓