CHL1

protein-coding

cell adhesion molecule L1 like, the group of Fibronectin type III domain containing|I-set domain containing|Ig-like cell adhesion molecule family

Gene summary

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]

MANE transcript

NM_006614.4

Inheritance

ClinVar variants

U:227B:60

Top phenotype

CHL1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr3:196,763-409,417

External References & Databases

Ensembl (ENSG00000134121)

Transcript & Mutation Effects

hg38 • Region Span ~212.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

partial deletion of the short arm of chromosome 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0016885

Submitter: Ambry Genetics

neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CHL1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 229

not providedTotal: 55

CHL1-related disorderTotal: 26

SeizureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006614.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	21 clinvar	7 clinvar	29
missense			222 clinvar	27 clinvar	5 clinvar	254
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	227	48	12	287

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006614.4	RefSeq	NP_006605.2	26	MANE Select
ENST00000256509.7	Ensembl	ENSP00000256509.2	26	MANE Select
NM_001253387.2	RefSeq	NP_001240316.1	25	Standard
NM_001253388.1	RefSeq	NP_001240317.1	25	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Splicing factor NOVA regulated synaptic proteins
Developmental Biology
CHL1 interactions
L1CAM interactions
Axon guidance

Biological Process

neuron migration
cell adhesion
signal transduction
axon guidance
adult locomotory behavior

Molecular Function

protease binding

Cellular Component

plasma membrane
integral component of membrane
dendrite
apical part of cell
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000256509
Coding exons: 26
Length: 212812
Individuals with no LoFs: 125693
Homozygous LoFs: 0
Heterozygous LoFs: 55
Defined: 125748
p: 0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.92	785	647	1.21	0.0000327	8005
Missense (PolyPhen)		243	247.66	0.98117		3137
Synonymous	-3.21	297	234	1.27	0.0000130	2288
Loss of Function	3.83	29	61.4	0.472	0.00000270	827

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00050	0.00049	rare
Ashkenazi Jewish	0.00032	0.00030	rare
East Asian	0.000056	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00017	0.00016	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Extracellular matrix and cell adhesion protein that plays a role in nervous system development and in synaptic plasticity. Both soluble and membranous forms promote neurite outgrowth of cerebellar and hippocampal neurons and suppress neuronal cell death. Plays a role in neuronal positioning of pyramidal neurons and in regulation of both the number of interneurons and the efficacy of GABAergic synapses. May play a role in regulating cell migration in nerve regeneration and cortical development. Potentiates integrin-dependent cell migration towards extracellular matrix proteins. Recruits ANK3 to the plasma membrane (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.0966

Intolerance Scores

LoFtool: 0.341
RVIS EVS: -0.16
RVIS percentile EVS: 41.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.356

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium