SEM1

Chr 7

SEM1 26S proteasome subunit

Also known as: C7orf76, DSS1, ECD, PSMD15, SHFD1, SHFM1, SHSF1, Shfdg1

NCBI Gene: 7979ENSG00000127922UniProt: Q6ZVN7

The product of this gene has been localized within the split hand/split foot malformation locus SHFM1 at chromosome 7. It has been proposed to be a candidate gene for the autosomal dominant form of the heterogeneous limb developmental disorder split hand/split foot malformation type 1. In addition, it has been shown to directly interact with BRCA2. It also may play a role in the completion of the cell cycle. [provided by RefSeq, Jul 2008]

28
ClinVar variants
18
Pathogenic / LP
0.76
pLI score
0
Active trials
Clinical Summary— SEM1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.76) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 8 VUS of 28 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.
0.63LOEUF
pLI 0.763
Z-score 2.02
OE 0.00 (0.00–0.63)
Moderately constrained

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.
0.55Z-score
OE missense 0.74 (0.55–1.03)
27 obs / 36.2 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.0.00 (0.00–0.63)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.55–1.03)
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.1.30
0≤1.21.6
LoF obs/exp: 0 / 4.8Missense obs/exp: 27 / 36.2Syn Z: -0.85

ClinVar Variant Classifications

28 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic1
VUS8
Likely Benign2
17
Pathogenic
1
Likely Pathogenic
8
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
1
0
1
VUS
0
3
5
0
8
Likely Benign
0
0
0
2
2
Benign
0
0
0
0
0
Total0323228

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

View in ClinVar →

Protein Context — Lollipop Plot

SEM1 · 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
SEM1 promotes tumor progression of glioblastoma via activating the akt signaling pathway.
Li C et al.·Cancer Lett
2023
Identifying and validating immunological biomarkers in obstructive sleep apnea through bioinformatics analysis.
Zhou EH et al.·Sci Rep
2025
SEM1, a homologue of the split hand/split foot malformation candidate gene Dss1, regulates exocytosis and pseudohyphal differentiation in yeast.
Jäntti J et al.·Proc Natl Acad Sci U S A
1999
Isolation and plasmid characterization of carbapenemase (IMP-4) producing Salmonella enterica Typhimurium from cats.
Abraham S et al.·Sci Rep
2016
Repurposing Hsp104 to Antagonize Seminal Amyloid and Counter HIV Infection.
Castellano LM et al.·Chem Biol
2015
The 26S proteasome drives trinucleotide repeat expansions.
Concannon C et al.·Nucleic Acids Res
2013
[Clinical feature and pathogenic analysis of a fetus with split hand-foot malformation].
Li C et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2020Case report
The Relationship Between the Level of Serum ESM-1 and Lp-PLA2 in Patients With Acute ST-Segment Elevation Myocardial Infarction.
Wei P et al.·Clin Transl Sci
2021Cohort
Test-Retest Reliability of Handgrip Strength as an Outcome Measure in Patients With Symptoms of Shoulder Impingement Syndrome.
Savva C et al.·J Manipulative Physiol Ther
2018Cohort
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