RGS19

Chr 20

regulator of G protein signaling 19

Also known as: GAIP, RGSGAIP

NCBI Gene: 10287 ENSG00000171700 UniProt: P49795 OMIM: 605071

The protein functions as a regulator of G-protein signaling by increasing GTPase activity of G protein alpha subunits, thereby terminating G protein-mediated cellular signaling pathways. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. This gene is highly constrained against loss-of-function variants (pLI 0.96, LOEUF 0.30), indicating that complete protein loss is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

G proteins mediate a number of cellular processes. The protein encoded by this gene belongs to the RGS (regulators of G-protein signaling) family and specifically interacts with G protein, GAI3. This protein is a guanosine triphosphatase-activating protein that functions to down-regulate Galpha i/Galpha q-linked signaling. Alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 0.29

Clinical Summary— RGS19

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

30 VUS of 36 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.29LOEUF

pLI 0.961

Z-score 2.95

OE 0.00 (0.00–0.29)

Highly constrained

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

Missense Constraint?

1.06Z-score

OE missense 0.76 (0.65–0.88)

114 obs / 150.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.29)

0≤0.351.4

Missense OE?0.76 (0.65–0.88)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 0 / 10.1Missense obs/exp: 114 / 150.7Syn Z: -0.88

ClinVar Variant Classifications

36 submitted variants in ClinVar

ClinVar

Classification Summary

VUS30

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	30	30
Likely Benign	1	1
Benign	0	0
Total	31	31

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

View in ClinVar →

37 pathogenic / likely-pathogenic (of 46) ClinVar copy-number / structural variants overlap RGS19 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →