SGSM3

Chr 22AR

small G protein signaling modulator 3

ENSG00000100359UniProt: Q96HU1

GTPase-activating protein (GAP) specific for Rab5 small GTPase for which it accelerates the intrinsic GTP hydrolysis rate, thereby controlling trafficking through the early endocytic pathway (PubMed:16086013, PubMed:17562788). May play a cooperative role in NF2-mediated growth suppression of cells

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 84MIM #620401
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SGSM3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.90LOEUF
pLI 0.000
Z-score 2.09
OE 0.66 (0.50–0.90)
Tolerant

Typical tolerance to LoF variation

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.
0.16Z-score
OE missense 0.98 (0.91–1.06)
475 obs / 485.0 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.0.66 (0.50–0.90)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.91–1.06)
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.1.15
0≤1.21.6
LoF obs/exp: 30 / 45.1Missense obs/exp: 475 / 485.0Syn Z: -1.72

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SGSM3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SGSM3-related intellectual disability

limited
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗
frameshift variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal recessive 84

MIM #620401

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
A Strong Candidate Gene for Nonsyndromic Intellectual Disability Phenotype: SGSM3.
Turkyilmaz A et al.·Clin Genet
2025🔓 Open Access
Intellectual disability syndrome associated with a homozygous founder variant in SGSM3 in Ashkenazi Jews.
Birnbaum R et al.·J Med Genet
2024
Small G protein signaling modulator 3 (SGSM3) knockdown attenuates apoptosis and cardiogenic differentiation in rat mesenchymal stem cells exposed to hypoxia.
Jung SE et al.·PLoS One
2020🔓 Open Access
Evaluation of 4-bp insertion/deletion polymorphism within the 3'UTR of SGSM3 in bladder cancer using mismatch PCR-RFLP method: A preliminary report.
Hashemi M et al.·J Cell Biochem
2018
Protective effects of kenpaullone on cardiomyocytes following H2O2-induced oxidative stress are attributed to inhibition of connexin 43 degradation by SGSM3.
Joo HC et al.·Biochem Biophys Res Commun
2018
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools