POP1

Chr 8AR

POP1 ribonuclease P/MRP subunit

Also known as: ANXD2

NCBI Gene: 10940 ENSG00000104356 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…

ARLOEUF 0.761 OMIM phenotype

Clinical Summary— POP1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

32 unique Pathogenic / Likely Pathogenic· 220 VUS of 506 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?

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

ClinVar Variant Classifications

506 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24

Likely Pathogenic8

VUS220

Likely Benign173

Benign60

Conflicting8

Pathogenic

Likely Pathogenic

220

VUS

173

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	20	3	1	0	24
Likely Pathogenic	7	1	0	0	8
VUS	1	211	7	1	220
Likely Benign	0	13	46	114	173
Benign	0	7	44	9	60
Conflicting	—				8
Total	28	235	98	124	493

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

View in ClinVar →

34 pathogenic / likely-pathogenic (of 38) ClinVar copy-number / structural variants overlap POP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →