IPCEF1

Chr 6

interaction protein for cytohesin exchange factors 1

Also known as: PIP3-E, PIP3E

NCBI Gene: 26034 ENSG00000074706 UniProt: Q8WWN9 OMIM: 619948

The protein enhances guanine-nucleotide exchange activity by PSCD2 on ARF6 and is predicted to have peroxidase activity involved in oxidative stress responses. The gene is moderately constrained against loss-of-function variants (LOEUF 0.655), but specific disease associations and inheritance patterns have not been established for this gene. Clinical significance of IPCEF1 variants remains to be determined.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable peroxidase activity and protein-macromolecule adaptor activity. Predicted to be involved in enzyme-linked receptor protein signaling pathway and response to oxidative stress. Predicted to be located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.66

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.66LOEUF

pLI 0.002

Z-score 2.83

OE 0.38 (0.23–0.66)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.23Z-score

OE missense 0.77 (0.68–0.87)

179 obs / 231.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.23–0.66)

0≤0.351.4

Missense OE?0.77 (0.68–0.87)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 9 / 24.0Missense obs/exp: 179 / 231.8Syn Z: 0.51

Background carrier burden — how many people carry a rare variant somewhere in IPCEF1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

481 rare PASS variants

Rare truncating (LoF)

1 in 3,900

63 rare PASS variants

Rare synonymous (reference)

1 in 240

187 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IPCEF1. 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 160	1 in 3,800
South Asian	~43k	1 in 150	1 in 1,700
Remaining (unassigned)	~30k	1 in 180	1 in 3,300
European (Finnish)	~27k	1 in 810	≈ 1 in 13,000
Admixed American	~22k	1 in 130	≈ 1 in 7,400
African / African American	~21k	1 in 180	≈ 1 in 9,200
East Asian	~20k	1 in 180	1 in 1,900
Ashkenazi Jewish	~13k	1 in 1,200	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 570	≈ 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): 9 of 10 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 10.? see exons ↓