SAMM50

Chr 22

SAMM50 sorting and assembly machinery component

Also known as: CGI-51, OMP85, SAM50, TOB55, TRG-3, YNL026W

NCBI Gene: 25813ENSG00000100347UniProt: Q9Y512

This gene encodes a component of the Sorting and Assembly Machinery (SAM) of the mitochondrial outer membrane. The Sam complex functions in the assembly of beta-barrel proteins into the outer mitochondrial membrane.[provided by RefSeq, Jun 2011]

165
ClinVar variants
52
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SAMM50
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
52 Pathogenic / Likely Pathogenic· 76 VUS of 165 total submissions

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.
0.89LOEUF
pLI 0.000
Z-score 2.01
OE 0.60 (0.41–0.89)
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.
0.92Z-score
OE missense 0.85 (0.76–0.94)
238 obs / 281.2 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.0.60 (0.41–0.89)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.76–0.94)
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.0.85
0≤1.21.6
LoF obs/exp: 18 / 29.9Missense obs/exp: 238 / 281.2Syn Z: 1.21

ClinVar Variant Classifications

165 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic51
Likely Pathogenic1
VUS76
Likely Benign5
Benign8
51
Pathogenic
1
Likely Pathogenic
76
VUS
5
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
51
0
51
Likely Pathogenic
0
0
1
0
1
VUS
0
72
4
0
76
Likely Benign
0
4
0
1
5
Benign
0
0
3
5
8
Total076596141

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

View in ClinVar →

Protein Context — Lollipop Plot

SAMM50 · 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
Effects of PNPLA3, TM6SF2 and SAMM50 on the development and severity of non-alcoholic fatty liver disease in children.
Lee KJ et al.·Pediatr Obes
2022
Newly identified single-nucleotide polymorphism associated with the transition from nonalcoholic fatty liver disease to liver fibrosis: results from a nested case-control study in the UK biobank.
Ling Y et al.·Ann Med
2025
The role of SAMM50 in non-alcoholic fatty liver disease: from genetics to mechanisms.
Li Z et al.·FEBS Open Bio
2021Functional
A comprehensive evaluation of candidate genetic polymorphisms in a large histologically characterized MASLD cohort using a novel framework.
Hakim A et al.·Hepatol Commun
2025Cohort
SAMM50 Affects Mitochondrial Morphology through the Association of Drp1 in Mammalian Cells.
Liu S et al.·FEBS Lett
2016
Genetic Variation of SAMM50 Is Not an Independent Risk Factor for Alcoholic Hepatocellular Carcinoma in Caucasian Patients.
Nischalke HD et al.·Int J Mol Sci
2022Cohort
PNPLA3 and SAMM50 variants are associated with lean nonalcoholic fatty liver disease in Asian population.
Lu CW et al.·Ann Hepatol
2025
PARVB and HSD17B13 variants are associated with nonalcoholic fatty liver disease in children.
Lee KJ et al.·J Gastroenterol Hepatol
2024
Mitochondria-related genes as prognostic signature of endometrial cancer and the effect of MACC1 on tumor cells.
Lin X et al.·PLoS One
2025
Targeted-bisulfite sequence analysis of the methylation of CpG islands in genes encoding PNPLA3, SAMM50, and PARVB of patients with non-alcoholic fatty liver disease.
Kitamoto T et al.·J Hepatol
2015Cohort
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