SERGEF

protein-coding

secretion regulating guanine nucleotide exchange factor

Gene summary

Predicted to enable guanyl-nucleotide exchange factor activity. Involved in negative regulation of protein secretion. Located in cytosol and nucleoplasm. Biomarker of atherosclerosis. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_012139.4

Inheritance

—

ClinVar variants

U:67B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr11:17,788,048-18,013,047

External References & Databases

Ensembl (ENSG00000129158)

Transcript & Mutation Effects

hg38 • Region Span ~225.0 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 SERGEF variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 68

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012139.4. 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						0
missense			65 clinvar	4 clinvar		69
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	67	4	0	71

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012139.4	RefSeq	NP_036271.1	11	MANE Select
ENST00000265965.10	Ensembl	ENSP00000265965.5	11	MANE Select
ENST00000524716.5	Ensembl	ENSP00000433884.1	2	Standard
ENST00000525422.5	Ensembl	ENSP00000434330.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

signal transduction
negative regulation of protein secretion

Molecular Function

Ran guanyl-nucleotide exchange factor activity
protein binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
aggresome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265965
Coding exons: 11
Length: 225115
Individuals with no LoFs: 125169
Homozygous LoFs: 1
Heterozygous LoFs: 578
Defined: 125748
p: 0.00230

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.472	217	237	0.914	0.0000116	2933
Missense (PolyPhen)		57	77.029	0.73998		940
Synonymous	0.780	84	93.6	0.897	0.00000487	912
Loss of Function	0.496	22	24.7	0.892	0.00000130	282

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0012	0.0012	notable
Latino/Admixed American	0.0021	0.0021	notable
Ashkenazi Jewish	0.0050	0.0050	notable
East Asian	0.00054	0.00054	rare
Finnish	0.00060	0.00060	rare
European (Non-Finnish)	0.0028	0.0027	notable
South Asian	0.0028	0.0028	notable
Other	0.0029	0.0029	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable guanine nucleotide exchange factor (GEF), which may be involved in the secretion process.;

Recessive Scores

pRec: 0.0925

Intolerance Scores

LoFtool: 0.559
RVIS EVS: 0.82
RVIS percentile EVS: 87.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0102

Gene Damage Prediction

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