POLRMT

Chr 19ADAR

RNA polymerase mitochondrial

Also known as: APOLMT, COXPD55, MTRNAP, MTRPOL, h-mtRPOL

This gene encodes the mitochondrial DNA-directed RNA polymerase that catalyzes transcription of mitochondrial DNA into RNA and synthesizes RNA primers necessary for mitochondrial DNA replication. Mutations cause combined oxidative phosphorylation deficiency 55, which can be inherited in either autosomal dominant or autosomal recessive patterns. The gene is extremely intolerant to loss-of-function variants (pLI near 1.0), indicating that complete loss of function is likely incompatible with life.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 55MIM #619743
ADAR
0
Active trials
23
Pubs (1 yr)
44
P/LP submissions
22%
P/LP missense
0.94
LOEUF
Mechanism
Clinical SummaryPOLRMT
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
41 unique Pathogenic / Likely Pathogenic· 352 VUS of 498 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.000
Z-score 1.89
OE 0.72 (0.560.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-1.87Z-score
OE missense 1.19 (1.121.25)
933 obs / 785.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.72 (0.560.94)
00.351.4
Missense OE1.19 (1.121.25)
00.61.4
Synonymous OE1.54
01.21.6
LoF obs/exp: 39 / 54.0Missense obs/exp: 933 / 785.7Syn Z: -8.07

ClinVar Variant Classifications

498 submitted variants in ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic8
VUS352
Likely Benign62
Benign10
Conflicting9
33
Pathogenic
8
Likely Pathogenic
352
VUS
62
Likely Benign
10
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
8
23
0
33
Likely Pathogenic
1
1
6
0
8
VUS
3
331
16
2
352
Likely Benign
1
31
5
25
62
Benign
0
5
3
2
10
Conflicting
9
Total73765329474

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

View in ClinVar →

Protein Context — Lollipop Plot

POLRMT · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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