HGH1

Chr 8

HGH1 cochaperone

ENSG00000235173 UniProt: Q9BTY7 OMIM: 620684

This co-chaperone protein facilitates the proper folding of eukaryotic elongation factor eEF2, an essential component of the cellular translation machinery, by recruiting chaperonin complexes to prevent misfolding during protein synthesis. Mutations cause autosomal recessive neurodevelopmental disorder with hypotonia, seizures, and intellectual disability. The gene shows tolerance to loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

OMIM ResearchSummary from UniProt

Co-chaperone involved in the folding of nascent eukaryotic elongation factor eEF2, an essential component of the translation machinery. Recognizes a non-native conformation in the central domain of eEF2 and recruits the chaperonin-containing T-complex (TRiC) to the C-terminal region of the nascent polypeptide, preventing unproductive interactions and promoting efficient folding of the N-terminal GTPase domain. May also assist in eEF2 maturation by recruiting the molecular chaperone Hsp90

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.69

Clinical Summary— HGH1

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.69LOEUF

pLI 0.012

Z-score 0.51

OE 0.73 (0.33–1.69)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.32Z-score

OE missense 1.17 (0.89–1.55)

34 obs / 29.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.73 (0.33–1.69)

0≤0.351.4

Missense OE?1.17 (0.89–1.55)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 3 / 4.1Missense obs/exp: 34 / 29.1Syn Z: 0.17

This gene — mechanism propensity

0.5672th %ile

GOF

0.75top 25%

LOF

0.2872th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.