SDC2

Chr 8

syndecan 2

Also known as: CD362, HSPG, HSPG1, SYND2

NCBI Gene: 6383 ENSG00000169439 UniProt: P34741 OMIM: 142460

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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein. The syndecan-2 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Altered syndecan-2 expression has been detected in several different tumor types. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.67

Clinical Summary— SDC2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.

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ClinVar Variants

26 VUS of 32 total submissions

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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 OE?0.21 (0.09–0.67)

0≤0.351.4

Missense OE?0.88 (0.74–1.04)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 2 / 9.4Missense obs/exp: 97 / 110.7Syn Z: -0.62

This gene — mechanism propensity

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

32 submitted variants in ClinVar

ClinVar

Classification Summary

VUS26

Benign1

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	26	26
Likely Benign	0	0
Benign	1	1
Total	27	27

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

View in ClinVar →

38 pathogenic / likely-pathogenic (of 39) ClinVar copy-number / structural variants overlap SDC2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →