PIF1

Chr 15

PIF1 5'-to-3' DNA helicase

Also known as: C15orf20, PIF

NCBI Gene: 80119 ENSG00000140451 UniProt: Q9H611

This gene encodes a DNA-dependent adenosine triphosphate (ATP)-metabolizing enzyme that functions as a 5' to 3' DNA helicase. The encoded protein can resolve G-quadruplex structures and RNA-DNA hybrids at the ends of chromosomes. It also prevents telomere elongation by inhibiting the actions of telomerase. Alternative splicing and the use of alternative start codons results in multiple isoforms that are differentially localized to either the mitochondria or the nucleus. [provided by RefSeq, Nov 2013]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.32

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.32LOEUF

pLI 0.000

Z-score 0.25

OE 0.95 (0.69–1.32)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.31Z-score

OE missense 0.95 (0.86–1.05)

297 obs / 312.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.95 (0.69–1.32)

0≤0.351.4

Missense OE?0.95 (0.86–1.05)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 25 / 26.4Missense obs/exp: 297 / 312.5Syn Z: 1.57

Background carrier burden — how many people carry a rare variant somewhere in PIF1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 41

1,058 rare PASS variants

Rare truncating (LoF)

1 in 590

181 rare PASS variants

Rare synonymous (reference)

1 in 110

427 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PIF1. 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 66	1 in 740
South Asian	~43k	1 in 37	1 in 530
Remaining (unassigned)	~30k	1 in 30	1 in 530
European (Finnish)	~27k	1 in 130	1 in 3,100
Admixed American	~22k	1 in 35	1 in 320
African / African American	~21k	1 in 38	1 in 300
East Asian	~20k	1 in 38	1 in 460
Ashkenazi Jewish	~13k	1 in 170	≈ 1 in 4,900
Middle Eastern	~2,884	1 in 40	≈ 1 in 720

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): 11 of 12 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 12.? see exons ↓