TM9SF2

Chr 13

transmembrane 9 superfamily member 2

Also known as: Lnc-PCIR, P76

NCBI Gene: 9375ENSG00000125304UniProt: Q99805

This gene encodes a member of the transmembrane 9 superfamily. The encoded 76 kDa protein localizes to early endosomes in human cells. The encoded protein possesses a conserved and highly hydrophobic C-terminal domain which contains nine transmembrane domains. The protein may play a role in small molecule transport or act as an ion channel. A pseudogene associated with this gene is located on the X chromosome. [provided by RefSeq, Oct 2012]

Research Assistant →
0
Active trials
5
Pubs (1 yr)
94
P/LP submissions
0%
P/LP missense
0.08
LOEUF· LoF intol.
—
Mechanism
Clinical Summary— TM9SF2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
94 unique Pathogenic / Likely Pathogenic· 49 VUS of 169 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.08LOEUF
pLI 1.000
Z-score 5.70
OE 0.00 (0.00–0.08)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.27Z-score
OE missense 0.52 (0.46–0.58)
189 obs / 365.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.08)
0≤0.351.4
Missense OE0.52 (0.46–0.58)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 0 / 37.8Missense obs/exp: 189 / 365.1Syn Z: -0.25

ClinVar Variant Classifications

169 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic92
Likely Pathogenic2
VUS49
Likely Benign3
92
Pathogenic
2
Likely Pathogenic
49
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
92
0
92
Likely Pathogenic
0
0
2
0
2
VUS
0
45
4
0
49
Likely Benign
0
3
0
0
3
Benign
0
0
0
0
0
Total048980146

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

View in ClinVar →

Protein Context — Lollipop Plot

TM9SF2 · 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
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 4 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