TMEM123

Chr 11

transmembrane protein 123

Also known as: KCT3, PORIMIN, PORMIN

NCBI Gene: 114908 ENSG00000152558 UniProt: Q8N131

This gene encodes a highly glycosylated transmembrane protein with a high content of threonine and serine residues in its extracellular domain, similar to a broadly defined category of proteins termed mucins. Exposure of some cell types to anti-PORIMIN (pro-oncosis receptor inducing membrane injury) antibody, crosslinks this protein on the cell surface and induces a type of cell death termed oncosis. Oncosis is distinct from apoptosis and is characterized by a loss of cell membrane integrity without DNA fragmentation. This gene product is proposed to function as a cell surface receptor that mediates cell death. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.62

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.62LOEUF

pLI 0.646

Z-score 2.22

OE 0.13 (0.05–0.62)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

-0.51Z-score

OE missense 1.14 (0.98–1.32)

124 obs / 108.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.13 (0.05–0.62)

0≤0.351.4

Missense OE?1.14 (0.98–1.32)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 1 / 7.6Missense obs/exp: 124 / 108.9Syn Z: -0.58

Background carrier burden — how many people carry a rare variant somewhere in TMEM123?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

339 rare PASS variants

Rare truncating (LoF)

1 in 2,500

63 rare PASS variants

Rare synonymous (reference)

1 in 530

130 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMEM123. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 210	1 in 2,600
South Asian	~43k	1 in 130	1 in 2,200
Remaining (unassigned)	~30k	1 in 150	≈ 1 in 7,300
European (Finnish)	~27k	1 in 430	1 in 2,900
Admixed American	~22k	1 in 120	1 in 3,200
African / African American	~21k	1 in 220	1 in 2,100
East Asian	~20k	1 in 170	1 in 3,200
Ashkenazi Jewish	~13k	1 in 960	none seen
Middle Eastern	~2,884	1 in 140	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 5 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 5.? see exons ↓