SDK2

Chr 17

sidekick cell adhesion molecule 2

NCBI Gene: 54549ENSG00000069188UniProt: Q58EX2

The protein encoded by this gene is a member of the immunoglobulin superfamily. The protein contains two immunoglobulin domains and thirteen fibronectin type III domains. Fibronectin type III domains are present in both extracellular and intracellular proteins and tandem repeats are known to contain binding sites for DNA, heparin and the cell surface. This protein, and a homologous mouse sequence, are very similar to the Drosophila sidekick gene product but the specific function of this superfamily member is not yet known. Evidence for alternative splicing at this gene locus has been observed but the full-length nature of additional variants has not yet been determined. [provided by RefSeq, Jul 2008]

0
Active trials
466
ClinVar variants
13
Pathogenic / LP
2.7
Missense Z
0.35
LOEUF
5
Pubs (2 yr)
Clinical Summary— SDK2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 393 VUS of 466 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.35LOEUF
pLI 0.004
Z-score 7.11
OE 0.25 (0.19–0.35)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.68Z-score
OE missense 0.79 (0.75–0.83)
1055 obs / 1329.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.25 (0.19–0.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.75–0.83)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 27 / 105.9Missense obs/exp: 1055 / 1329.8Syn Z: -0.53

ClinVar Variant Classifications

466 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic1
VUS393
Likely Benign42
Benign18
12
Pathogenic
1
Likely Pathogenic
393
VUS
42
Likely Benign
18
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
1
0
1
VUS
0
392
1
0
393
Likely Benign
0
9
9
24
42
Benign
0
5
0
13
18
Total04062337466

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

View in ClinVar →

Protein Context — Lollipop Plot

SDK2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Genome Sequencing in 19 Families With Bladder Exstrophy and Epispadias Complex Indicates Involvement of the ADGR-Gene Family.
Nordenskjöld A et al.·Am J Med Genet A
2026
Laboratory and genetic characteristic associated with gallbladder-related outcomes in sickle cell disease in Brazil: results from the REDS-III multicenter cohort study
Belisário AR et al.·Ann Hematol
2026Cohort
Comparative transcriptome analysis identified genes involved in testicular development in Takifugu rubripes.
Chen J et al.·Fish Physiol Biochem
2025
Gene-gene interaction analysis for age at onset of bipolar disorder in a Korean population.
Park M et al.·J Affect Disord
2024
Methylome-wide association study of adolescent depressive episode with psychotic symptoms and childhood trauma.
Sun Y et al.·J Affect Disord
2024
Dissecting super-enhancer driven transcriptional dependencies reveals novel therapeutic strategies and targets for group 3 subtype medulloblastoma
Li M et al.·J Exp Clin Cancer Res
2022
The cell adhesion molecule Sdk1 shapes assembly of a retinal circuit that detects localized edges
Rochon PL et al.·Elife
2021
Connected in diversity: Isotopic analysis refines provenance for Islamic plant-ash glass from the eastern Silk Roads
Lü QQ et al.·iScience
2023
Top 8 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

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