SURF4

Chr 9

surfeit 4

Also known as: ERV29

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 SummarySURF4
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.61) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.55LOEUF
pLI 0.606
Z-score 2.60
OE 0.17 (0.070.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.11Z-score
OE missense 0.53 (0.440.63)
82 obs / 156.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.17 (0.070.55)
00.351.4
Missense OE0.53 (0.440.63)
00.61.4
Synonymous OE0.92
01.21.6
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

0 submitted variants 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

No active trials found for this gene.

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Clinical Literature
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