STIP1

Chr 11

stress induced phosphoprotein 1

Also known as: HEL-S-94n, HOP, IEF-SSP-3521, P60, STI1, STI1L

NCBI Gene: 10963 ENSG00000168439 UniProt: P31948

STIP1 encodes a co-chaperone protein that coordinates HSP70 and HSP90 molecular chaperones in protein folding by mediating their association and regulating their ATPase activities. The gene is highly constrained against loss-of-function variants (pLI 0.9998, LOEUF 0.201), but no human disease has been definitively associated with STIP1 mutations to date.

ResearchSummary from RefSeq, UniProt

STIP1 is an adaptor protein that coordinates the functions of HSP70 (see HSPA1A; MIM 140550) and HSP90 (see HSP90AA1; MIM 140571) in protein folding. It is thought to assist in the transfer of proteins from HSP70 to HSP90 by binding both HSP90 and substrate-bound HSP70. STIP1 also stimulates the ATPase activity of HSP70 and inhibits the ATPase activity of HSP90, suggesting that it regulates both the conformations and ATPase cycles of these chaperones (Song and Masison, 2005 [PubMed 16100115]).[supplied by OMIM, Jul 2009]

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

0.20

LOEUF· LoF intol.

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.20LOEUF

pLI 1.000

Z-score 5.31

OE 0.08 (0.03–0.20)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.92Z-score

OE missense 0.70 (0.63–0.78)

223 obs / 319.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.08 (0.03–0.20)

0≤0.351.4

Missense OE?0.70 (0.63–0.78)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 3 / 38.6Missense obs/exp: 223 / 319.6Syn Z: -1.14

Background carrier burden — how many people carry a rare variant somewhere in STIP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

697 rare PASS variants

Rare truncating (LoF)

1 in 920

65 rare PASS variants

Rare synonymous (reference)

1 in 140

322 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for STIP1. 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 180	1 in 1,400
South Asian	~43k	1 in 110	1 in 5,900
Remaining (unassigned)	~30k	1 in 120	1 in 780
European (Finnish)	~27k	1 in 370	1 in 2,500
Admixed American	~22k	1 in 160	1 in 900
African / African American	~21k	1 in 120	1 in 1,400
East Asian	~20k	1 in 120	1 in 1,200
Ashkenazi Jewish	~13k	1 in 370	1 in 1,700
Middle Eastern	~2,884	1 in 170	≈ 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): 14 of 14 coding exons well covered in gnomAD exomes. Genomes: 13 of 14 (exon 1 below).? see exons ↓