PIWIL4

Chr 11

piwi like RNA-mediated gene silencing 4

Also known as: HIWI2, MIWI2

NCBI Gene: 143689 ENSG00000134627 UniProt: Q7Z3Z4

PIWIL4 belongs to the Argonaute family of proteins, which function in development and maintenance of germline stem cells (Sasaki et al., 2003 [PubMed 12906857]).[supplied by OMIM, Mar 2008]

Research

PIWIL4 belongs to the Argonaute family of proteins, which function in development and maintenance of germline stem cells (Sasaki et al., 2003 [PubMed 12906857]).[supplied by OMIM, Mar 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.58

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.58LOEUF

pLI 0.000

Z-score 3.79

OE 0.39 (0.27–0.58)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.49Z-score

OE missense 0.81 (0.74–0.88)

377 obs / 467.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.27–0.58)

0≤0.351.4

Missense OE?0.81 (0.74–0.88)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 18 / 45.6Missense obs/exp: 377 / 467.6Syn Z: 1.14

Background carrier burden — how many people carry a rare variant somewhere in PIWIL4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 56

967 rare PASS variants

Rare truncating (LoF)

1 in 1,300

133 rare PASS variants

Rare synonymous (reference)

1 in 89

377 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PIWIL4. 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 77	1 in 1,700
South Asian	~43k	1 in 54	1 in 710
Remaining (unassigned)	~30k	1 in 56	1 in 1,900
European (Finnish)	~27k	1 in 130	≈ 1 in 27,000
Admixed American	~22k	1 in 65	1 in 2,200
African / African American	~21k	1 in 54	1 in 480
East Asian	~20k	1 in 75	1 in 380
Ashkenazi Jewish	~13k	1 in 210	none seen
Middle Eastern	~2,884	1 in 55	≈ 1 in 2,900

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): 19 of 20 coding exons well covered in gnomAD exomes; exon 13 marginal. Genomes: all 20.? see exons ↓