SYNDIG1

Chr 20

synapse differentiation inducing 1

Also known as: C20orf39, DSPC2, IFITMD5, TMEM90B

NCBI Gene: 79953ENSG00000101463UniProt: Q9H7V2

This gene encodes a transmembrane protein that regulates AMPA receptor content at developing synapses and plays a role in postsynaptic development and maturation. Mutations cause autosomal recessive intellectual disability with seizures and language delay, typically presenting in early childhood. The gene shows moderate tolerance to loss-of-function variants.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
17
P/LP submissions
0%
P/LP missense
0.77
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— SYNDIG1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 46 VUS of 73 total submissions
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
0.77LOEUF
pLI 0.302
Z-score 2.01
OE 0.24 (0.10–0.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.51Z-score
OE missense 0.89 (0.77–1.02)
141 obs / 159.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.24 (0.10–0.77)
0≤0.351.4
Missense OE0.89 (0.77–1.02)
0≤0.61.4
Synonymous OE0.90
0≤1.21.6
LoF obs/exp: 2 / 8.2Missense obs/exp: 141 / 159.0Syn Z: 0.65
DN
0.76top 25%
GOF
0.78top 25%
LOF
0.3454th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

73 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic3
VUS46
Likely Benign3
14
Pathogenic
3
Likely Pathogenic
46
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
3
0
3
VUS
0
43
3
0
46
Likely Benign
0
0
3
0
3
Benign
0
0
0
0
0
Total04323066

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

View in ClinVar →

Protein Context — Lollipop Plot

SYNDIG1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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