SURF4

Chr 9

surfeit 4

Also known as: ERV29

NCBI Gene: 6836ENSG00000148248UniProt: O15260OMIM: 185660

The SURF4 protein functions as an endoplasmic reticulum cargo receptor that mediates the export of lipoproteins and other secreted proteins by recruiting them into COPII vesicles for secretion from the cell. Mutations cause a neurodevelopmental disorder with intellectual disability through a predicted gain-of-function mechanism, though the inheritance pattern has not been definitively established. The pathogenicity likely results from disrupted lipoprotein secretion and altered ER-Golgi trafficking affecting normal cellular homeostasis.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
GOFmechanismLOEUF 0.55
Clinical Summary— SURF4
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.61) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 40 VUS of 86 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.55LOEUF
pLI 0.606
Z-score 2.60
OE 0.17 (0.07–0.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.11Z-score
OE missense 0.53 (0.44–0.63)
82 obs / 156.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.17 (0.07–0.55)
0≤0.351.4
Missense OE0.53 (0.44–0.63)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 2 / 11.5Missense obs/exp: 82 / 156.1Syn Z: 0.49
DN
0.5868th %ile
GOF
0.6638th %ile
LOF
0.3940th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

86 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic1
VUS40
Likely Benign1
35
Pathogenic
1
Likely Pathogenic
40
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
1
0
1
VUS
1
30
9
0
40
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total13145077

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SURF4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SURF4 inhibits autophagy to enhance lung adenocarcinoma progression and stemness through Hedgehog pathway regulation.
Zhou J et al.·Tissue Cell
2026
Intestinal SURF4 in dyslipidaemia and female-specific metabolic disorders: insights from rats with polycystic ovary syndrome.
Xu Y et al.·Front Nutr
2025Open Access
NAD+ Metabolism-Mediated SURF4-STING Axis Enhances T-Cell Anti-Tumor Effects in the Ovarian Cancer Microenvironment.
Shen J et al.·Cell Death Dis
2025Open Access
[High expression of SURF4 promotes migration, invasion and proliferation of gastric cancer cells by inhibiting tight junction proteins].
Wang Z et al.·Nan Fang Yi Ke Da Xue Xue Bao
2025
Identification of SURF4 and RALGAPA1 as promising therapeutic targets in glioblastoma and pan-cancer through integrative multi-omics, CRISPR-Cas9 screening and prognostic meta-analysis.
Wang F et al.·Cancer Immunol Immunother
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients