CHL1

Chr 3

cell adhesion molecule L1 like

Also known as: CALL, L1CAM2

NCBI Gene: 10752 ENSG00000134121 UniProt: Q96FC9

This gene encodes a neural cell adhesion molecule that facilitates cell recognition and signal transduction in the nervous system. Mutations cause an autosomal recessive developmental disorder characterized by intellectual disability, seizures, and congenital heart defects, with some patients also showing cohesinopathy-like features including growth retardation and limb malformations. The gene is highly constrained against loss-of-function variants, indicating that both copies are essential for normal neurodevelopment.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the L1 gene family of neural cell adhesion molecules. It is a neural recognition molecule that may be involved in signal transduction pathways. The deletion of one copy of this gene may be responsible for mental defects in patients with 3p- syndrome. This protein may also play a role in the growth of certain cancers. Alternate splicing results in both coding and non-coding variants. [provided by RefSeq, Nov 2011]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtWarsaw breakage syndrome

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.64

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?

0.64LOEUF

pLI 0.000

Z-score 3.83

OE 0.47 (0.35–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-1.92Z-score

OE missense 1.21 (1.14–1.29)

785 obs / 647.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.47 (0.35–0.64)

0≤0.351.4

Missense OE?1.21 (1.14–1.29)

0≤0.61.4

Synonymous OE?1.27

0≤1.21.6

LoF obs/exp: 29 / 61.4Missense obs/exp: 785 / 647.3Syn Z: -3.21

Background carrier burden — how many people carry a rare variant somewhere in CHL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 34

1,953 rare PASS variants

Rare truncating (LoF)

1 in 1,900

172 rare PASS variants

Rare synonymous (reference)

1 in 63

661 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CHL1. 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 2,000
South Asian	~43k	1 in 34	1 in 850
Remaining (unassigned)	~30k	1 in 29	1 in 3,000
European (Finnish)	~27k	1 in 130	1 in 4,400
Admixed American	~22k	1 in 36	1 in 1,300
African / African American	~21k	1 in 27	1 in 1,700
East Asian	~20k	1 in 37	1 in 1,300
Ashkenazi Jewish	~13k	1 in 140	≈ 1 in 3,200
Middle Eastern	~2,884	1 in 33	≈ 1 in 1,400

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): 21 of 26 coding exons well covered in gnomAD exomes; exons 3, 21, 23, 25, 27 marginal. Genomes: all 26.? see exons ↓