SYNPO

Chr 5

synaptopodin

Also known as: SYNPO1

NCBI Gene: 11346ENSG00000171992UniProt: Q8N3V7

Synaptopodin is an actin-associated protein that may play a role in actin-based cell shape and motility. The name synaptopodin derives from the protein's associations with postsynaptic densities and dendritic spines and with renal podocytes (Mundel et al., 1997 [PubMed 9314539]).[supplied by OMIM, Mar 2008]

374
ClinVar variants
10
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— SYNPO
🧬
Gene-Disease Validity (ClinGen)
focal segmental glomerulosclerosis · ADLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 262 VUS of 374 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.30LOEUF
pLI 0.986
Z-score 4.19
OE 0.11 (0.05–0.30)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
0.93Z-score
OE missense 0.89 (0.82–0.96)
496 obs / 558.1 exp
Tolerant

Mild missense constraint

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.0.11 (0.05–0.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.82–0.96)
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.0.96
0≤1.21.6
LoF obs/exp: 3 / 26.1Missense obs/exp: 496 / 558.1Syn Z: 0.50

ClinVar Variant Classifications

374 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
VUS262
Likely Benign72
Benign22
Conflicting8
10
Pathogenic
262
VUS
72
Likely Benign
22
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
0
0
0
VUS
2
244
16
0
262
Likely Benign
0
9
6
57
72
Benign
0
6
8
8
22
Conflicting
—8
Total22594065374

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

View in ClinVar →

Protein Context — Lollipop Plot

SYNPO · 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
SYNAPTOPODIN; SYNPO
MIM #608155 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Calcium overload via PVT1 reprograms neutrophil fate and constrains gastric cancer progression.
Wang D et al.·J Transl Med
2025
Integrated Bioinformatics and Clinical Correlation Analysis of Key Genes, Pathways, and Potential Therapeutic Agents Related to Diabetic Nephropathy.
Chen S et al.·Dis Markers
2022
Identification of key carcinogenic genes in Wilms' tumor.
He S et al.·Genes Genet Syst
2021
Functional analysis of promoter mutations in the ACTN4 and SYNPO genes in focal segmental glomerulosclerosis.
Dai S et al.·Nephrol Dial Transplant
2010Functional
Intrinsic disorder and amino acid specificity modulate binding of the WW2 domain in kidney and brain protein (KIBRA) to synaptopodin.
Kwok E et al.·J Biol Chem
2019
Effects of SGLT2 inhibitors on patients with diabetic kidney disease: A preliminary study on the basis of podocyturia.
Durcan E et al.·J Diabetes
2022Cohort
Machine-learning-driven biomarker discovery for the discrimination between allergic and irritant contact dermatitis.
Fortino V et al.·Proc Natl Acad Sci U S A
2020
Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodin.
Huber TB et al.·J Clin Invest
2006Functional
Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease.
Ribeiro PC et al.·Stem Cell Res Ther
2020
Exome Sequence Data From Multigenerational Families Implicate AMPA Receptor Trafficking in Neurocognitive Impairment and Schizophrenia Risk.
Kos MZ et al.·Schizophr Bull
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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