TM2D2

Chr 8

TM2 domain containing 2

Also known as: BLP1

NCBI Gene: 83877 ENSG00000169490 UniProt: Q9BX73 OMIM: 610081

The protein encoded by this gene contains a structural module related to that of the seven transmembrane domain G protein-coupled receptor superfamily. This protein has sequence and structural similarities to the beta-amyloid binding protein (BBP), but, unlike BBP, it does not regulate a response to beta-amyloid peptide. This protein may have regulatory roles in cell death or proliferation signal cascades. This gene has multiple alternatively spliced transcript variants which encode two different isoforms. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.02

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.02LOEUF

pLI 0.006

Z-score 1.54

OE 0.48 (0.25–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.48Z-score

OE missense 0.88 (0.75–1.03)

105 obs / 119.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.48 (0.25–1.02)

0≤0.351.4

Missense OE?0.88 (0.75–1.03)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 5 / 10.3Missense obs/exp: 105 / 119.8Syn Z: 0.42

Background carrier burden — how many people carry a rare variant somewhere in TM2D2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

336 rare PASS variants

Rare truncating (LoF)

1 in 1,800

52 rare PASS variants

Rare synonymous (reference)

1 in 670

139 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TM2D2. 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 330	1 in 1,600
South Asian	~43k	1 in 99	1 in 7,200
Remaining (unassigned)	~30k	1 in 280	1 in 2,500
European (Finnish)	~27k	1 in 890	≈ 1 in 27,000
Admixed American	~22k	1 in 200	≈ 1 in 5,300
African / African American	~21k	1 in 240	1 in 1,700
East Asian	~20k	1 in 230	≈ 1 in 9,900
Ashkenazi Jewish	~13k	≈ 1 in 6,500	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 220	≈ 1 in 2,900

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): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓