CHAC1

Chr 15

ChaC glutathione specific gamma-glutamylcyclotransferase 1

NCBI Gene: 79094 ENSG00000128965 UniProt: Q9BUX1

This gene encodes a member of the gamma-glutamylcyclotransferase family of proteins. The encoded protein has been shown to promote neuronal differentiation by deglycination of the Notch receptor, which prevents receptor maturation and inhibits Notch signaling. This protein may also play a role in the unfolded protein response, and in regulation of glutathione levels and oxidative balance in the cell. Elevated expression of this gene may indicate increased risk of cancer recurrence among breast and ovarian cancer patients. [provided by RefSeq, Sep 2016]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.25

LOEUF

—

Mechanism

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?

1.25LOEUF

pLI 0.000

Z-score 1.00

OE 0.67 (0.38–1.25)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.24Z-score

OE missense 0.95 (0.83–1.08)

152 obs / 160.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.67 (0.38–1.25)

0≤0.351.4

Missense OE?0.95 (0.83–1.08)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 7 / 10.5Missense obs/exp: 152 / 160.7Syn Z: -0.22

Background carrier burden — how many people carry a rare variant somewhere in CHAC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

297 rare PASS variants

Rare truncating (LoF)

1 in 2,900

40 rare PASS variants

Rare synonymous (reference)

1 in 270

156 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CHAC1. 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 110	1 in 2,600
South Asian	~43k	1 in 520	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 100	1 in 3,400
European (Finnish)	~27k	1 in 620	none seen
Admixed American	~22k	1 in 130	1 in 2,500
African / African American	~21k	1 in 230	1 in 1,700
East Asian	~20k	1 in 190	1 in 2,800
Ashkenazi Jewish	~13k	1 in 1,000	none seen
Middle Eastern	~2,884	1 in 480	none seen

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): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓