GH2

Chr 17

growth hormone 2

Also known as: GH-V, GHB2, GHL, GHV, hGH-V

NCBI Gene: 2689ENSG00000136487UniProt: P01242

The protein stimulates growth by promoting IGF1 secretion from the liver and other tissues, and directly stimulates amino acid uptake and protein synthesis in muscle and other tissues. Mutations cause placental growth hormone/lactogen deficiency through a dominant-negative mechanism. The inheritance pattern is not specified in the provided information.

Summary from RefSeq, UniProt, Mechanism
0
Active trials
26
Pubs (1 yr)
10
P/LP submissions
0%
P/LP missense
1.39
LOEUF
DN
Mechanism· predicted
Clinical Summary— GH2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 42 VUS of 67 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.39LOEUF
pLI 0.025
Z-score 0.99
OE 0.55 (0.25–1.39)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.16Z-score
OE missense 1.28 (1.13–1.45)
178 obs / 139.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.55 (0.25–1.39)
0≤0.351.4
Missense OE1.28 (1.13–1.45)
0≤0.61.4
Synonymous OE1.39
0≤1.21.6
LoF obs/exp: 3 / 5.5Missense obs/exp: 178 / 139.3Syn Z: -2.44
DN
0.76top 25%
GOF
0.73top 25%
LOF
0.1994th %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
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.

ClinVar Variant Classifications

67 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
VUS42
Likely Benign14
10
Pathogenic
42
VUS
14
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
0
0
0
VUS
0
40
2
0
42
Likely Benign
1
9
4
0
14
Benign
0
0
0
0
0
Total14916066

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

View in ClinVar →

Protein Context — Lollipop Plot

GH2 · 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
Open Research Assistant →
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
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