GTPBP4

Chr 10

GTP binding protein 4

Also known as: CRFG, NGB, NOG1

NCBI Gene: 23560 ENSG00000107937 UniProt: Q9BZE4 OMIM: 619169

This protein functions as a GTPase involved in 60S ribosomal subunit biogenesis and acts as a TP53 repressor to prevent cell cycle arrest. Mutations cause autosomal recessive intellectual disability with microcephaly and growth retardation. The gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.08), indicating intolerance to haploinsufficiency in the general population.

OMIM ResearchSummary from RefSeq, UniProt

GTP-binding proteins are GTPases and function as molecular switches that can flip between two states: active, when GTP is bound, and inactive, when GDP is bound. 'Active' in this context usually means that the molecule acts as a signal to trigger other events in the cell. When an extracellular ligand binds to a G-protein-linked receptor, the receptor changes its conformation and switches on the trimeric G proteins that associate with it by causing them to eject their GDP and replace it with GTP. The switch is turned off when the G protein hydrolyzes its own bound GTP, converting it back to GDP. But before that occurs, the active protein has an opportunity to diffuse away from the receptor and deliver its message for a prolonged period to its downstream target. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

LOF

Mechanism· predicted

Some data sources returned errors (1)

gnomad: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in GTPBP4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 57

907 rare PASS variants

Rare truncating (LoF)

1 in 8,100

37 rare PASS variants

Rare synonymous (reference)

1 in 150

296 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GTPBP4. 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 95	1 in 14,000
South Asian	~43k	1 in 66	≈ 1 in 21,000
Remaining (unassigned)	~30k	1 in 58	1 in 6,000
European (Finnish)	~27k	1 in 290	≈ 1 in 27,000
Admixed American	~22k	1 in 60	≈ 1 in 7,300
African / African American	~21k	1 in 58	≈ 1 in 21,000
East Asian	~20k	1 in 92	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 250	1 in 480
Middle Eastern	~2,884	1 in 58	none seen

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): 6 of 17 coding exons well covered in gnomAD exomes; exons 2, 3, 5, 6, 8 and 6 more marginal. Genomes: all 17.? see exons ↓