IPCEF1

protein-coding

interaction protein for cytohesin exchange factors 1, the group of Pleckstrin homology domain containing

Gene summary

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]

MANE transcript

NM_001130700.2

Inheritance

—

ClinVar variants

U:33B:4

Top phenotype

Tramadol response

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr6:154,154,496-154,356,803

External References & Databases

Ensembl (ENSG00000074706)

Transcript & Mutation Effects

hg38 • Region Span ~202.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IPCEF1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 34

Tramadol responseTotal: 10

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001130700.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar			2
missense			31 clinvar	3 clinvar	1 clinvar	35
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	33	3	1	37

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001130700.2	RefSeq	NP_001124172.1	10	MANE Select
ENST00000367220.9	Ensembl	ENSP00000356189.4	10	MANE Select
NM_001130699.2	RefSeq	NP_001124171.1	10	Standard
NM_001394799.1	RefSeq	NP_001381728.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Arf6 signaling events

Biological Process

response to oxidative stress
oxygen transport
cellular oxidant detoxification

Molecular Function

peroxidase activity
oxygen carrier activity
protein binding
protein domain specific binding

Cellular Component

cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000422970
Coding exons: 10
Length: 202296
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125745
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.23	179	232	0.772	0.0000117	2875
Missense (PolyPhen)		38	72.702	0.52268		919
Synonymous	0.506	85	91.1	0.933	0.00000500	818
Loss of Function	2.83	9	24.0	0.376	0.00000128	284

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.000035	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Enhances the promotion of guanine-nucleotide exchange by PSCD2 on ARF6 in a concentration-dependent manner. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.544
RVIS EVS: 0.33
RVIS percentile EVS: 73.41

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.902

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium