POP1

Chr 8AR

POP1 ribonuclease P/MRP subunit

Also known as: ANXD2

NCBI Gene: 10940 ENSG00000104356 UniProt: Q8WXC3 OMIM: 602486

The protein functions as a ribonuclease that processes pre-RNA in both the endoribonuclease for mitochondrial RNA processing complex and the ribonuclease P complex. Mutations cause anauxetic dysplasia 2, a skeletal dysplasia syndrome, with autosomal recessive inheritance. This gene shows low constraint against loss-of-function variants (pLI near 0), suggesting tolerance to such changes in the general population.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the protein subunit of two different small nucleolar ribonucleoprotein complexes: the endoribonuclease for mitochondrial RNA processing complex and the ribonuclease P complex. The encoded protein is a ribonuclease that localizes to the nucleus and functions in pre-RNA processing. This protein is also an autoantigen in patients suffering from connective tissue diseases. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Anauxetic dysplasia 2MIM #617396

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Anauxetic dysplasia 2; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.76

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.76LOEUF

pLI 0.000

Z-score 2.97

OE 0.56 (0.41–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.12Z-score

OE missense 0.87 (0.81–0.94)

495 obs / 570.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.41–0.76)

0≤0.351.4

Missense OE?0.87 (0.81–0.94)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 29 / 52.2Missense obs/exp: 495 / 570.3Syn Z: 1.28

Background carrier burden — how many people carry a rare variant somewhere in POP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 41

1,195 rare PASS variants

Rare truncating (LoF)

1 in 530

182 rare PASS variants

Rare synonymous (reference)

1 in 110

468 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for POP1. 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 59	1 in 510
South Asian	~43k	1 in 46	1 in 380
Remaining (unassigned)	~30k	1 in 42	1 in 640
European (Finnish)	~27k	1 in 140	1 in 1,400
Admixed American	~22k	1 in 44	1 in 1,100
African / African American	~21k	1 in 33	1 in 450
East Asian	~20k	1 in 49	1 in 470
Ashkenazi Jewish	~13k	1 in 240	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 56	≈ 1 in 1,400

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 15 coding exons well covered in gnomAD exomes and genomes.? see exons ↓