POLR2M

Chr 15

RNA polymerase II subunit M

Also known as: GRINL1A, Gdown, Gdown1

NCBI Gene: 81488 ENSG00000255529 UniProt: P0CAP2 OMIM: 606485

This gene encodes a subunit of a specific form of RNA polymerase II termed Pol II(G). The encoded protein may act as a negative regulator of transcriptional activation by the Mediator complex. Alternative splicing results in multiple transcript variants. There is a pseudogene for this gene on chromosome 4. Readthrough transcription between this gene and the neighboring upstream gene MYZAP (myocardial zonula adherens protein) is represented with GeneID 145781. [provided by RefSeq, Oct 2013]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.73

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.73LOEUF

pLI 0.031

Z-score 2.30

OE 0.35 (0.18–0.73)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.85Z-score

OE missense 1.17 (1.05–1.30)

240 obs / 205.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.35 (0.18–0.73)

0≤0.351.4

Missense OE?1.17 (1.05–1.30)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 5 / 14.4Missense obs/exp: 240 / 205.9Syn Z: -0.27

Background carrier burden — how many people carry a rare variant somewhere in POLR2M?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 81

620 rare PASS variants

Rare truncating (LoF)

1 in 2,700

65 rare PASS variants

Rare synonymous (reference)

1 in 180

187 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for POLR2M. 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 120	1 in 2,100
South Asian	~43k	1 in 58	1 in 3,500
Remaining (unassigned)	~30k	1 in 65	1 in 3,200
European (Finnish)	~27k	1 in 250	≈ 1 in 27,000
Admixed American	~22k	1 in 53	1 in 3,900
African / African American	~21k	1 in 79	1 in 3,000
East Asian	~20k	1 in 94	1 in 1,900
Ashkenazi Jewish	~13k	1 in 510	none seen
Middle Eastern	~2,884	1 in 87	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 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓