HGH1

Chr 8

HGH1 cochaperone

Also known as: BRP16, BRP16L, C8orf30A, C8orf30B, FAM203A, FAM203B

NCBI Gene: 51236 ENSG00000235173 UniProt: Q9BTY7

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.

ResearchSummary from UniProt

Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.69

LOEUF

GOF

Mechanism· predicted

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?

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

Background carrier burden — how many people carry a rare variant somewhere in HGH1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 86

677 rare PASS variants

Rare truncating (LoF)

1 in 1,400

107 rare PASS variants

Rare synonymous (reference)

1 in 230

282 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for HGH1. 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 98	1 in 1,400
South Asian	~43k	1 in 92	1 in 1,100
Remaining (unassigned)	~30k	1 in 58	1 in 1,600
European (Finnish)	~27k	1 in 180	1 in 830
Admixed American	~22k	1 in 60	1 in 630
African / African American	~21k	1 in 72	1 in 1,300
East Asian	~20k	1 in 120	1 in 990
Ashkenazi Jewish	~13k	1 in 360	≈ 1 in 2,600
Middle Eastern	~2,881	1 in 95	≈ 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): 5 of 6 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 6.? see exons ↓