TM9SF2

Chr 13

transmembrane 9 superfamily member 2

Also known as: Lnc-PCIR, P76

The protein functions as a channel or small molecule transporter in intracellular compartments, particularly localizing to early endosomes. Mutations cause autosomal recessive intellectual disability with behavioral abnormalities and craniofacial dysmorphism. This gene is highly constrained against loss-of-function variants, suggesting complete loss of protein function is likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.08
Clinical SummaryTM9SF2
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.08LOEUF
pLI 1.000
Z-score 5.70
OE 0.00 (0.000.08)
Highly constrained

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

Missense Constraint
3.27Z-score
OE missense 0.52 (0.460.58)
189 obs / 365.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.000.08)
00.351.4
Missense OE0.52 (0.460.58)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 0 / 37.8Missense obs/exp: 189 / 365.1Syn Z: -0.25

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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