TMEM132A

Chr 11

transmembrane protein 132A

Also known as: GBP, HSPA5BP1

NCBI Gene: 54972 ENSG00000006118 UniProt: Q24JP5

The protein encoded by this gene may function in embryonic and postnatal brain development and regulates glial fibrillary acidic protein (GFAP) gene expression through STAT3 phosphorylation. Mutations cause autosomal recessive intellectual disability with seizures and language delay, typically manifesting in early childhood. This gene is not highly constrained against loss-of-function variants.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein that is highly similar to the rat Grp78-binding protein (GBP). Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.80

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

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.000

Z-score 2.50

OE 0.55 (0.39–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.80Z-score

OE missense 0.91 (0.85–0.98)

590 obs / 647.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.55 (0.39–0.80)

0≤0.351.4

Missense OE?0.91 (0.85–0.98)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 20 / 36.3Missense obs/exp: 590 / 647.0Syn Z: 1.93

Background carrier burden — how many people carry a rare variant somewhere in TMEM132A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 37

1,406 rare PASS variants

Rare truncating (LoF)

1 in 1,400

158 rare PASS variants

Rare synonymous (reference)

1 in 72

604 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMEM132A. 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 47	1 in 1,800
South Asian	~43k	1 in 33	1 in 850
Remaining (unassigned)	~30k	1 in 34	1 in 2,500
European (Finnish)	~27k	1 in 110	1 in 630
Admixed American	~22k	1 in 36	1 in 680
African / African American	~21k	1 in 27	1 in 1,100
East Asian	~20k	1 in 30	1 in 1,100
Ashkenazi Jewish	~13k	1 in 210	1 in 1,500
Middle Eastern	~2,884	1 in 31	≈ 1 in 1,200

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 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓