SDC2

Chr 8

syndecan 2

Also known as: CD362, HSPG, HSPG1, SYND2

NCBI Gene: 6383ENSG00000169439UniProt: P34741

The encoded protein is a transmembrane heparan sulfate proteoglycan that functions as a cell surface receptor regulating dendritic arbor morphogenesis, cell proliferation, migration, and cell-matrix interactions. Mutations in SDC2 cause neurodevelopmental disorder with seizures and speech delay, inherited in an autosomal recessive pattern. The gene is moderately constrained against loss-of-function mutations.

Summary from RefSeq, UniProt
Research Assistant →
2
Active trials
44
Pubs (1 yr)
38
P/LP submissions
0%
P/LP missense
0.67
LOEUF
DN
Mechanism· predicted
Clinical Summary— SDC2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.
📋
ClinVar Variants
38 unique Pathogenic / Likely Pathogenic· 27 VUS of 71 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
0.67LOEUF
pLI 0.405
Z-score 2.23
OE 0.21 (0.09–0.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.46Z-score
OE missense 0.88 (0.74–1.04)
97 obs / 110.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.21 (0.09–0.67)
0≤0.351.4
Missense OE0.88 (0.74–1.04)
0≤0.61.4
Synonymous OE1.12
0≤1.21.6
LoF obs/exp: 2 / 9.4Missense obs/exp: 97 / 110.7Syn Z: -0.62
DN
0.7230th %ile
GOF
0.4974th %ile
LOF
0.3647th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

71 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic2
VUS27
Benign1
36
Pathogenic
2
Likely Pathogenic
27
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
36
0
36
Likely Pathogenic
0
0
2
0
2
VUS
0
26
1
0
27
Likely Benign
0
0
0
0
0
Benign
0
1
0
0
1
Total02739066

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

View in ClinVar →

Protein Context — Lollipop Plot

SDC2 · 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
SDC2 and TFPI2 Methylation in Stool Samples as an Integrated Biomarker for Early Detection of Colorectal Cancer
Zhang W et al.·Cancer Manag Res
2021
Comparative detection of syndecan-2 methylation in preoperative and postoperative stool DNA in patients with colorectal cancer
Song JH et al.·World J Gastrointest Surg
2023Cohort
The Application Value of Syndecan-2 Gene Methylation for Colorectal Cancer Diagnosis: A Clinical Study and Meta-Analyses
Yue C et al.·Front Med (Lausanne)
2022
The stool syndecan2 methylation test is more robust than blood tests for methylated septin9, CEA, CA19-9 and CA724: a diagnostic test for the early detection of colorectal neoplasms
Zhan Y et al.·Transl Cancer Res
2023
Combining methylated SDC2 test in stool DNA, fecal immunochemical test, and tumor markers improves early detection of colorectal neoplasms
Zeng T et al.·Front Oncol
2023
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
A study on the correlation between DNA methylation and protein expression levels of SDC2 in patients with colorectal cancer and its clinicopathological significance.
Han Y et al.·J Int Med Res
2026Open AccessCohort
Stool-based SDC2/SFRP2/TFPI2 methylation assay for colorectal neoplasia screening: a multicenter, case-control study.
Li X et al.·Front Oncol
2026Open Access
Fecal DNA SDC2 methylation test for colorectal cancer diagnosis: A systematic review and meta-analysis.
Liu X et al.·Biomol Biomed
2026Review
Stool DNA-based SDC2 Methylation Test for the Screening of Colorectal Neoplasia in an Asymptomatic, Average-Risk Population.
Choi HI et al.·Korean J Gastroenterol
2026Open Access
Evaluating the cross-reactivity of a stool methylated syndecan-2 (meSDC2) test in colorectal cancer detection.
Hong SW et al.·J Gastrointest Oncol
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