CNTN5

Chr 11

contactin 5

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

NCBI Gene: 53942 ENSG00000149972 UniProt: O94779 OMIM: 607219

This protein is a GPI-anchored cell adhesion molecule that mediates cell surface interactions and axon connections during nervous system development, with particular involvement in auditory system function. CNTN5 is highly constrained against loss-of-function variants (pLI near 1, LOEUF 0.485), indicating that mutations are likely to cause significant developmental effects. Pathogenic variants cause autosomal recessive intellectual disability with language impairment and autistic features.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.48

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

-0.34Z-score

OE missense 1.04 (0.97–1.11)

599 obs / 576.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.33 (0.23–0.48)

0≤0.351.4

Missense OE?1.04 (0.97–1.11)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 18 / 55.0Missense obs/exp: 599 / 576.3Syn Z: -1.77

Background carrier burden — how many people carry a rare variant somewhere in CNTN5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 34

1,602 rare PASS variants

Rare truncating (LoF)

1 in 390

174 rare PASS variants

Rare synonymous (reference)

1 in 77

549 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CNTN5. 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 47	1 in 630
South Asian	~43k	1 in 35	1 in 460
Remaining (unassigned)	~30k	1 in 34	1 in 320
European (Finnish)	~27k	1 in 120	1 in 470
Admixed American	~22k	1 in 40	1 in 220
African / African American	~21k	1 in 34	1 in 370
East Asian	~20k	1 in 36	1 in 420
Ashkenazi Jewish	~13k	1 in 81	1 in 990
Middle Eastern	~2,884	1 in 33	1 in 410

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 21 of 23 coding exons well covered in gnomAD exomes; exons 3, 9 marginal. Genomes: all 23.? see exons ↓