SNCAIP

Chr 5

synuclein alpha interacting protein

Also known as: SYPH1, Sph1

NCBI Gene: 9627ENSG00000064692UniProt: Q9Y6H5

This gene encodes a protein containing several protein-protein interaction domains, including ankyrin-like repeats, a coiled-coil domain, and an ATP/GTP-binding motif. The encoded protein interacts with alpha-synuclein in neuronal tissue and may play a role in the formation of cytoplasmic inclusions and neurodegeneration. A mutation in this gene has been associated with Parkinson's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

Primary Disease Associations & Inheritance

UniProtParkinson disease
222
ClinVar variants
21
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SNCAIP
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 153 VUS of 222 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.
0.55LOEUF
pLI 0.000
Z-score 3.70
OE 0.35 (0.23–0.55)
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.
0.77Z-score
OE missense 0.90 (0.83–0.98)
438 obs / 485.5 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.0.35 (0.23–0.55)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.83–0.98)
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.0.98
0≤1.21.6
LoF obs/exp: 13 / 37.4Missense obs/exp: 438 / 485.5Syn Z: 0.25

ClinVar Variant Classifications

222 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic1
VUS153
Likely Benign34
Benign12
Conflicting2
20
Pathogenic
1
Likely Pathogenic
153
VUS
34
Likely Benign
12
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
1
0
1
VUS
1
115
27
10
153
Likely Benign
0
13
5
16
34
Benign
0
3
2
7
12
Conflicting
—2
Total11315533222

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

View in ClinVar →

Protein Context — Lollipop Plot

SNCAIP · 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
Identification of sixteen novel candidate genes for late onset Parkinson's disease.
Gialluisi A et al.·Mol Neurodegener
2021
Molecular Stratification of Medulloblastoma: Clinical Outcomes and Therapeutic Interventions.
Sursal T et al.·Anticancer Res
2022Review
Identification of Parkinson's disease candidate genes using CAESAR and screening of MAPT and SNCAIP in South African Parkinson's disease patients.
Keyser RJ et al.·J Neural Transm (Vienna)
2011Cohort
Robust molecular subgrouping and reference-free aneuploidy detection in medulloblastoma using low-depth whole genome bisulfite sequencing.
Thompson D et al.·Acta Neuropathol Commun
2025
Organization of the human synphilin-1 gene, a candidate for Parkinson's disease.
Engelender S et al.·Mamm Genome
2000
Genome-Wide Association Study of Event-Free Survival in Diffuse Large B-Cell Lymphoma Treated With Immunochemotherapy.
Ghesquieres H et al.·J Clin Oncol
2015Meta-analysis
Mutation Analysis of the Genes Associated with Parkinson's Disease in a Finnish Cohort of Early-Onset Dementia.
Luukkainen L et al.·J Alzheimers Dis
2020Cohort
Elucidate biomarkers and the molecular pathways associated with genetic variants that contribute to the etiology of Parkinson's disease.
Nguyen HD·Acta Neurol Belg
2025
Genomic Analysis Reveals Novel Specific Metastatic Mutations in Chinese Clear Cell Renal Cell Carcinoma.
Meng H et al.·Biomed Res Int
2020
Genome-Wide Survey for Microdeletions or -Duplications in 155 Patients with Lower Urinary Tract Obstructions (LUTO).
Schierbaum LM et al.·Genes (Basel)
2021Cohort
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