POLR2G

Chr 11

RNA polymerase II subunit G

Also known as: RPB19, RPB7, hRPB19, hsRPB7

NCBI Gene: 5436 ENSG00000168002 UniProt: P62487

The protein is a core subunit of RNA polymerase II that synthesizes messenger RNA and many functional non-coding RNAs, forming a subcomplex that helps regulate DNA access to the polymerase active site. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, developmental delay, and speech impairment. This gene is extremely intolerant to loss-of-function mutations, indicating that even single functional copies are critical for normal development.

ResearchSummary from RefSeq, UniProt

This gene encodes the seventh largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The protein functions in transcription initiation, and is also thought to help stabilize transcribing polyermase molecules during elongation. [provided by RefSeq, Jan 2009]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.42

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?

1.42LOEUF

pLI 0.000

Z-score 0.51

OE 0.84 (0.52–1.42)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

2.09Z-score

OE missense 0.41 (0.32–0.53)

41 obs / 99.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.84 (0.52–1.42)

0≤0.351.4

Missense OE?0.41 (0.32–0.53)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 10 / 11.9Missense obs/exp: 41 / 99.6Syn Z: -0.02

Background carrier burden — how many people carry a rare variant somewhere in POLR2G?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 1,300

132 rare PASS variants

Rare truncating (LoF)

1 in 3,100

41 rare PASS variants

Rare synonymous (reference)

1 in 470

86 rare PASS variants

Rare missense and truncating variants are carried at similar rates in POLR2G; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 8 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 1,500	1 in 3,700
South Asian	~43k	1 in 2,200	1 in 2,700
Remaining (unassigned)	~30k	1 in 1,100	≈ 1 in 7,500
European (Finnish)	~27k	1 in 2,700	1 in 2,100
Admixed American	~22k	1 in 490	≈ 1 in 7,600
African / African American	~21k	1 in 1,200	1 in 3,300
East Asian	~20k	1 in 590	1 in 2,300
Ashkenazi Jewish	~13k	1 in 580	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): 7 of 8 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 8.? see exons ↓