GH1

Chr 17ARAD

growth hormone 1

Also known as: GH, GH-N, GHB5, GHN, IGHD1A, IGHD1B, IGHD2, hGH

NCBI Gene: 2688ENSG00000259384UniProt: P01241

The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. This particular family member is expressed in the pituitary but not in placental tissue as is the case for the other four genes in the growth hormone locus. Mutations in or deletions of the gene lead to growth hormone deficiency and short stature. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Growth hormone deficiency, isolated, type IAMIM #262400
AR
Growth hormone deficiency, isolated, type IBMIM #612781
Growth hormone deficiency, isolated, type IIMIM #173100
AD
Kowarski syndromeMIM #262650
AR
0
Active trials
42
Pathogenic / LP
219
ClinVar variants
5
Pubs (1 yr)
-0.9
Missense Z
0.91
LOEUF
Clinical Summary— GH1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
42 Pathogenic / Likely Pathogenic· 99 VUS of 219 total submissions
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GeneReview available — GH1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.91LOEUF
pLI 0.030
Z-score 1.76
OE 0.40 (0.20–0.91)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.94Z-score
OE missense 1.24 (1.09–1.42)
148 obs / 119.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.40 (0.20–0.91)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.24 (1.09–1.42)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.48
0≤1.21.6
LoF obs/exp: 4 / 10.0Missense obs/exp: 148 / 119.1Syn Z: -2.80
DN
0.78top 25%
GOF
0.75top 25%
LOF
0.1697th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median · 1 literature citation
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.

Literature Evidence

DNAffected individuals have a guanine to adenine transition at the first nucleotide of exon 3 (E3+1 G->A) that results in exon skipping and production of a dominant-negative 17.5-kDa isoform.PMID:18554279

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

ClinVar Variant Classifications

219 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic7
VUS99
Likely Benign52
Benign12
Conflicting14
35
Pathogenic
7
Likely Pathogenic
99
VUS
52
Likely Benign
12
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
6
22
0
35
Likely Pathogenic
1
6
0
0
7
VUS
2
73
19
5
99
Likely Benign
0
6
23
23
52
Benign
0
0
12
0
12
Conflicting
—14
Total10917628219

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

View in ClinVar →

Protein Context — Lollipop Plot

GH1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
A Cold-Adapted GH1 β-Glucosidase from Paenibacillus cellulosilyticus with high methanol tolerance for efficient biotransformation of ginsenoside Rb1 to minor ginsenoside F2.
Liu H et al.·Int J Biol Macromol
2026
Growth hormone deficiency in three siblings homozygous for a rare GH1 haplotype.
Ribeiro AC et al.·Front Endocrinol (Lausanne)
2025Open Access
Genome-wide analysis and functional validation of the GH1 gene family in cotton under salt stress.
Zhang L et al.·Funct Integr Genomics
2025Functional
GH1 Gene Polymorphisms Reveal Population-Level Allele Variation in North African (Clarias gariepinus) and Bighead Catfish (Clarias macrocephalus).
Thammachak P et al.·Genes (Basel)
2025Open Access
Probiotic Levilactobacillus brevis GH1 from baijiu Daqu enhanced γ-aminobutyric acid and antioxidant ability in Cordyceps militaris fruiting body extract and brown rice beverage.
Shen K et al.·Curr Res Food Sci
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients