CGNL1

protein-coding

cingulin like 1

Gene summary

This gene encodes a member of the cingulin family. The encoded protein localizes to both adherens and tight cell-cell junctions and mediates junction assembly and maintenance by regulating the activity of the small GTPases RhoA and Rac1. Heterozygous chromosomal rearrangements resulting in association of the promoter for this gene with the aromatase gene are a cause of aromatase excess syndrome. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Nov 2011]

MANE transcript

NM_032866.5

Inheritance

—

ClinVar variants

P:1U:245B:29

Top phenotype

CGNL1-related disorder

gnomAD constraint

pLI —, LoF o/e 1.01

Max pathogenic AF

—

Genomic locus

chr15:57,375,967-57,550,717

External References & Databases

Ensembl (ENSG00000128849)

Transcript & Mutation Effects

hg38 • Region Span ~174.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CGNL1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 244

CGNL1-related disorderTotal: 21

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032866.5. 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		7 clinvar	3 clinvar	11
missense			239 clinvar	18 clinvar	1 clinvar	258
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	1	245	25	4	275

Highest pathogenic variant AF is 0.0000024784345

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 56 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032866.5	RefSeq	NP_116255.2	18	MANE Select
ENST00000281282.6	Ensembl	ENSP00000281282.5	18	MANE Select
NM_001252335.2	RefSeq	NP_001239264.1	18	Standard
ENST00000860576.1	Ensembl	ENSP00000530635.1	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Tight junction - Homo sapiens (human)

Biological Process

actin filament organization
negative regulation of small GTPase mediated signal transduction

Molecular Function

motor activity
protein binding

Cellular Component

bicellular tight junction
myosin complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000281282
Coding exons: 18
Length: 174761
Individuals with no LoFs: 125541
Homozygous LoFs: 1
Heterozygous LoFs: 206
Defined: 125748
p: 0.000823

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.02	881	728	1.21	0.0000442	8553
Missense (PolyPhen)		242	211.99	1.1416		2541
Synonymous	-0.870	320	301	1.06	0.0000189	2468
Loss of Function	-0.0509	63	62.6	1.01	0.00000349	748

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00075	0.00074	rare
Latino/Admixed American	0.0023	0.0023	notable
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00092	0.00092	rare
Finnish	0.00037	0.00037	rare
European (Non-Finnish)	0.00042	0.00041	rare
South Asian	0.00085	0.00085	rare
Other	0.0026	0.0026	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in anchoring the apical junctional complex, especially tight junctions, to actin-based cytoskeletons. {ECO:0000269|PubMed:22891260}.;
Disease: DISEASE: Aromatase excess syndrome (AEXS) [MIM:139300]: An autosomal dominant disorder characterized by increased extraglandular aromatization of steroids that presents with heterosexual precocity in males and isosexual precocity in females. {ECO:0000269|PubMed:12736278}. Note=The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration inv(15)(q21.2;q21.3) has been found in patients with aromatase excess syndrome. The inversion moves the promoter of the CGNL1 gene into a 5-prime position in relation to the aromatase coding region.;

Recessive Scores

pRec: 0.117

Intolerance Scores

LoFtool: 0.903
RVIS EVS: 0.33
RVIS percentile EVS: 73.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.735

Gene Damage Prediction

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