PIAS1

Chr 15

protein inhibitor of activated STAT 1

Also known as: DDXBP1, GBP, GU/RH-II, ZMIZ3

NCBI Gene: 8554 ENSG00000033800 UniProt: O75925 OMIM: 603566

This gene encodes a member of the protein inhibitor of activated STAT (PIAS) family. PIAS proteins function as SUMO E3 ligases and play important roles in many cellular processes by mediating the sumoylation of target proteins. This protein plays a central role as a transcriptional coregulator of numerous cellular pathways includign the STAT1 and nuclear factor kappaB pathways. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.09

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.09LOEUF

pLI 1.000

Z-score 5.22

OE 0.00 (0.00–0.09)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

2.72Z-score

OE missense 0.59 (0.53–0.66)

205 obs / 347.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.09)

0≤0.351.4

Missense OE?0.59 (0.53–0.66)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 0 / 31.8Missense obs/exp: 205 / 347.8Syn Z: -1.58

Background carrier burden — how many people carry a rare variant somewhere in PIAS1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 230

603 rare PASS variants

Rare truncating (LoF)

1 in 6,500

30 rare PASS variants

Rare synonymous (reference)

1 in 120

325 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PIAS1. 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 280	1 in 7,600
South Asian	~43k	1 in 170	1 in 2,900
Remaining (unassigned)	~30k	1 in 170	≈ 1 in 30,000
European (Finnish)	~27k	1 in 830	≈ 1 in 26,000
Admixed American	~22k	1 in 150	≈ 1 in 5,700
African / African American	~21k	1 in 170	1 in 3,600
East Asian	~20k	1 in 180	≈ 1 in 19,000
Ashkenazi Jewish	~13k	1 in 350	none seen
Middle Eastern	~2,884	1 in 220	none seen

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): 7 of 14 coding exons well covered in gnomAD exomes; exon 13 poorly covered; exons 4, 5, 7, 8, 9, 10 marginal. Genomes: all 14.? see exons ↓