CRTC2

Chr 1

CREB regulated transcription coactivator 2

Also known as: TORC-2, TORC2

NCBI Gene: 200186 ENSG00000160741 UniProt: Q53ET0 OMIM: 608972

This gene encodes a member of the transducers of regulated cAMP response element-binding protein activity family of transcription coactivators. These proteins promote the transcription of genes targeted by the cAMP response element-binding protein, and therefore play an important role in many cellular processes. Under basal conditions the encoded protein is phosphorylated by AMP-activated protein kinase or the salt-inducible kinases and is sequestered in the cytoplasm. Upon activation by elevated cAMP or calcium, the encoded protein translocates to the nucleus and increases target gene expression. Single nucleotide polymorphisms in this gene may increase the risk of type 2 diabetes. A pseudogene of this gene is located on the long arm of chromosome 5. [provided by RefSeq, Dec 2010]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.23

Clinical Summary— CRTC2

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

77 VUS of 107 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.23LOEUF

pLI 0.999

Z-score 4.84

OE 0.09 (0.04–0.23)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.77Z-score

OE missense 0.89 (0.82–0.97)

356 obs / 399.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.04–0.23)

0≤0.351.4

Missense OE?0.89 (0.82–0.97)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 3 / 33.0Missense obs/exp: 356 / 399.3Syn Z: -0.36

This gene — mechanism propensity

0.4388th %ile

GOF

0.4184th %ile

LOF

0.81top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.23

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

107 submitted variants in ClinVar

ClinVar

Classification Summary

VUS77

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	1	76	77
Likely Benign	0	1	1
Benign	0	0	0
Total	1	77	78

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

16 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap CRTC2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →