POLR3K

Chr 16AR

RNA polymerase III subunit K

Also known as: C11, C11-RNP3, HLD21, My010, RPC10, RPC11, RPC12.5

NCBI Gene: 51728 ENSG00000161980 UniProt: Q9Y2Y1 OMIM: 606007

The protein functions as a core component of RNA polymerase III, which synthesizes transfer RNAs and small ribosomal RNAs, and monitors transcription fidelity by cleaving mis-incorporated nucleotides. Mutations cause hypomyelinating leukodystrophy-7 with or without oligodontia, a childhood-onset disorder affecting white matter development and sometimes tooth formation, inherited in an autosomal recessive pattern. The gene shows moderate tolerance to loss-of-function variants (LOEUF 1.228), consistent with the recessive inheritance pattern observed clinically.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a small essential subunit of RNA polymerase III, the polymerase responsible for synthesizing transfer and small ribosomal RNAs in eukaryotes. The carboxy-terminal domain of this subunit shares a high degree of sequence similarity to the carboxy-terminal domain of an RNA polymerase II elongation factor. This similarity in sequence is supported by functional studies showing that this subunit is required for proper pausing and termination during transcription. Pseudogenes of this gene are found on chromosomes 13 and 17.[provided by RefSeq, Jul 2010]

OMIM ResearchGenerating clinical summary…

ARLOEUF 1.231 OMIM phenotype

Clinical Summary— POLR3K

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Gene-Disease Validity (ClinGen)

leukodystrophy, hypomyelinating, 21 · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Low constraint (pLI 0.11) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 16 VUS of 25 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?

1.23LOEUF

pLI 0.108

Z-score 1.26

OE 0.39 (0.16–1.23)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.09Z-score

OE missense 1.03 (0.85–1.26)

70 obs / 67.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.39 (0.16–1.23)

0≤0.351.4

Missense OE?1.03 (0.85–1.26)

0≤0.61.4

Synonymous OE?1.26

0≤1.21.6

LoF obs/exp: 2 / 5.1Missense obs/exp: 70 / 67.9Syn Z: -1.01

ClinVar Variant Classifications

25 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

VUS16

Likely Benign4

Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	1	0	3
Likely Pathogenic	0	0	0	0
VUS	15	1	0	16
Likely Benign	0	0	4	4
Benign	0	0	0	0
Total	17	2	4	23

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

View in ClinVar →

45 pathogenic / likely-pathogenic (of 60) ClinVar copy-number / structural variants overlap POLR3K — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →