CGNL1

Chr 15

cingulin like 1

Also known as: JACOP, PCING

NCBI Gene: 84952 ENSG00000128849 UniProt: Q0VF96

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]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtAromatase excess syndrome

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.24

LOEUF

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?

1.24LOEUF

pLI 0.000

Z-score -0.05

OE 1.01 (0.82–1.24)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.02Z-score

OE missense 1.21 (1.14–1.28)

881 obs / 728.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.01 (0.82–1.24)

0≤0.351.4

Missense OE?1.21 (1.14–1.28)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 63 / 62.6Missense obs/exp: 881 / 728.0Syn Z: -0.87

Background carrier burden — how many people carry a rare variant somewhere in CGNL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 24

1,984 rare PASS variants

Rare truncating (LoF)

1 in 840

260 rare PASS variants

Rare synonymous (reference)

1 in 57

726 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CGNL1. 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 32	1 in 1,200
South Asian	~43k	1 in 29	1 in 400
Remaining (unassigned)	~30k	1 in 21	1 in 890
European (Finnish)	~27k	1 in 67	1 in 1,700
Admixed American	~22k	1 in 27	1 in 380
African / African American	~21k	1 in 23	1 in 980
East Asian	~20k	1 in 29	1 in 530
Ashkenazi Jewish	~13k	1 in 130	1 in 1,400
Middle Eastern	~2,884	1 in 25	1 in 360

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): 15 of 18 coding exons well covered in gnomAD exomes; exons 4, 5, 14 marginal. Genomes: all 18.? see exons ↓