SMIM5

Chr 17

small integral membrane protein 5

Also known as: C17orf109, PP12104

NCBI Gene: 643008ENSG00000204323UniProt: Q71RC9

The protein is predicted to be membrane-localized, but its specific cellular function remains unknown. No established disease associations or inheritance patterns have been reported for SMIM5 mutations. The predicted gain-of-function mechanism suggests that pathogenic variants may result in protein overactivity, though clinical phenotypes associated with SMIM5 mutations have not been characterized.

Summary from RefSeq, Mechanism
Research Assistant →
0
Active trials
1
Pubs (1 yr)
14
P/LP submissions
0%
P/LP missense
1.79
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— SMIM5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.13) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
14 unique Pathogenic / Likely Pathogenic· 21 VUS of 38 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.79LOEUF
pLI 0.133
Z-score 0.54
OE 0.56 (0.18–1.79)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.19Z-score
OE missense 0.92 (0.71–1.20)
40 obs / 43.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.56 (0.18–1.79)
0≤0.351.4
Missense OE0.92 (0.71–1.20)
0≤0.61.4
Synonymous OE0.85
0≤1.21.6
LoF obs/exp: 1 / 1.8Missense obs/exp: 40 / 43.5Syn Z: 0.54
DN
0.75top 25%
GOF
0.78top 25%
LOF
0.2485th %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

38 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic1
VUS21
Likely Benign2
13
Pathogenic
1
Likely Pathogenic
21
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
1
0
1
VUS
0
17
4
0
21
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Total01818137

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

View in ClinVar →

Protein Context — Lollipop Plot

SMIM5 · 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.

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Clinical Literature
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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

No open access results found

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