SDF4

Chr 1

stromal cell derived factor 4

Also known as: Cab45, SDF-4

NCBI Gene: 51150ENSG00000078808UniProt: Q9BRK5

The protein is a stromal cell-derived factor containing calcium-binding motifs that localizes to the Golgi lumen and may regulate calcium-dependent cellular activities in the endoplasmic reticulum and post-ER compartments. Mutations cause autosomal recessive spastic tetraplegia with thin corpus callosum and progressive microcephaly, affecting the central nervous system with early childhood onset. The gene shows relatively low constraint to loss-of-function variation.

Summary from RefSeq, UniProt
Research Assistant →
2
Active trials
5
Pubs (1 yr)
137
P/LP submissions
0%
P/LP missense
0.76
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— SDF4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
130 unique Pathogenic / Likely Pathogenic· 95 VUS of 247 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.76LOEUF
pLI 0.009
Z-score 2.24
OE 0.39 (0.21–0.76)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.55Z-score
OE missense 0.90 (0.81–1.01)
227 obs / 251.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.39 (0.21–0.76)
0≤0.351.4
Missense OE0.90 (0.81–1.01)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 6 / 15.5Missense obs/exp: 227 / 251.7Syn Z: -0.46
DN
0.73top 25%
GOF
0.6443th %ile
LOF
0.2484th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
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

247 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic124
Likely Pathogenic6
VUS95
Likely Benign6
Benign2
124
Pathogenic
6
Likely Pathogenic
95
VUS
6
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
124
0
124
Likely Pathogenic
0
0
6
0
6
VUS
1
65
29
0
95
Likely Benign
0
5
1
0
6
Benign
0
0
1
1
2
Total1701611233

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

View in ClinVar →

Protein Context — Lollipop Plot

SDF4 · protein map & ClinVar variants

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

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 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
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