GTPBP8

Chr 3

GTP binding protein 8

Also known as: HSPC135, MRX8

NCBI Gene: 29083 ENSG00000163607 UniProt: Q8N3Z3 OMIM: 621553

GTPBP8 encodes a mitochondrial GTPase that binds GTP and metal ions. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, typically presenting in infancy. The gene is highly constrained against loss-of-function variants, indicating its critical importance for normal development.

OMIM ResearchSummary from RefSeq

Predicted to enable GTP binding activity; GTPase activity; and metal ion binding activity. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 1.51

Clinical Summary— GTPBP8

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

44 VUS of 57 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.51LOEUF

pLI 0.000

Z-score 0.26

OE 0.92 (0.58–1.51)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.56Z-score

OE missense 1.13 (1.00–1.28)

173 obs / 153.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.92 (0.58–1.51)

0≤0.351.4

Missense OE?1.13 (1.00–1.28)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 11 / 12.0Missense obs/exp: 173 / 153.3Syn Z: -0.48

ClinVar Variant Classifications

57 submitted variants in ClinVar

ClinVar

Classification Summary

VUS44

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	44	44
Likely Benign	3	3
Benign	0	0
Total	47	47

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

28 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap GTPBP8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →