RGS22

Chr 8

regulator of G protein signaling 22

Also known as: CT145, PRTD-NY2

NCBI Gene: 26166 ENSG00000132554 UniProt: Q8NE09 OMIM: 615650

The RGS22 protein inhibits G-protein signaling by increasing the GTPase activity of G protein alpha subunits, driving them into their inactive GDP-bound form. Mutations in RGS22 cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and developmental regression. The gene shows minimal constraint against loss-of-function variants in population databases.

OMIM ResearchSummary from RefSeq, UniProt

Enables G-protein alpha-subunit binding activity. Predicted to be involved in negative regulation of signal transduction. Located in actin cytoskeleton; cytosol; and fibrillar center. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.96

Clinical Summary— RGS22

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

142 VUS of 172 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.96LOEUF

pLI 0.000

Z-score 1.86

OE 0.76 (0.62–0.96)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.41Z-score

OE missense 0.95 (0.89–1.02)

580 obs / 608.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.76 (0.62–0.96)

0≤0.351.4

Missense OE?0.95 (0.89–1.02)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 56 / 73.2Missense obs/exp: 580 / 608.3Syn Z: 1.01

ClinVar Variant Classifications

172 submitted variants in ClinVar

ClinVar

Classification Summary

VUS142

Likely Benign12

Benign4

142

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	0	142	0	142
Likely Benign	0	10	2	12
Benign	1	0	3	4
Total	1	152	5	158

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

View in ClinVar →

36 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap RGS22 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →