GHRHR

Chr 7AR

growth hormone releasing hormone receptor

Also known as: GHRFR, GRFR, IGHD1B, IGHD4

NCBI Gene: 2692ENSG00000106128UniProt: Q02643

This gene encodes a receptor for growth hormone-releasing hormone. Binding of this hormone to the receptor leads to synthesis and release of growth hormone. Mutations in this gene have been associated with isolated growth hormone deficiency (IGHD), also known as Dwarfism of Sindh, a disorder characterized by short stature. [provided by RefSeq, Jun 2010]

Primary Disease Associations & Inheritance

Growth hormone deficiency, isolated, type IVMIM #618157
AR
375
ClinVar variants
65
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GHRHR
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
65 Pathogenic / Likely Pathogenic· 129 VUS of 375 total submissions

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.
0.93LOEUF
pLI 0.000
Z-score 1.82
OE 0.60 (0.40–0.93)
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.
-0.50Z-score
OE missense 1.09 (0.98–1.21)
262 obs / 240.3 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.0.60 (0.40–0.93)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.09 (0.98–1.21)
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.1.23
0≤1.21.6
LoF obs/exp: 15 / 24.8Missense obs/exp: 262 / 240.3Syn Z: -1.77

ClinVar Variant Classifications

375 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic21
VUS129
Likely Benign121
Benign39
Conflicting21
44
Pathogenic
21
Likely Pathogenic
129
VUS
121
Likely Benign
39
Benign
21
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
5
29
1
44
Likely Pathogenic
4
10
7
0
21
VUS
3
95
26
5
129
Likely Benign
0
7
54
60
121
Benign
0
4
32
3
39
Conflicting
—21
Total1612114869375

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

View in ClinVar →

Protein Context — Lollipop Plot

GHRHR · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Growth hormone deficiency, isolated, type IV

MIM #618157

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — GHRHR
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
GHRH and the prostate.
Muñoz-Moreno L et al.·Rev Endocr Metab Disord
2025Review
Diseases associated with growth hormone-releasing hormone receptor (GHRHR) mutations.
Martari M et al.·Prog Mol Biol Transl Sci
2009Review
Isolated growth hormone deficiency.
Hernández LM et al.·Pituitary
2007Review
Identification of genetic variants and phenotypic characterization of a large cohort of patients with congenital hypopituitarism and related disorders.
Gregory LC et al.·Genet Med
2023Cohort
Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes.
Kırkgöz T et al.·Arch Endocrinol Metab
2023Cohort
Signaling mechanism of growth hormone-releasing hormone receptor.
Halmos G et al.·Vitam Horm
2023Review
Genetic evaluation of short stature.
Wit JM et al.·Best Pract Res Clin Endocrinol Metab
2011Review
Growth hormone treatment outcomes in children with genetic isolated growth hormone deficiency.
Aouchiche K et al.·Eur J Pediatr
2025
Contribution of functionally assessed GHRHR mutations to idiopathic isolated growth hormone deficiency in patients without GH1 mutations.
Cohen E et al.·Hum Mutat
2019Cohort
Pathogenic and likely pathogenic genetic alterations and polymorphisms in growth hormone gene (GH1) and growth hormone releasing hormone receptor gene (GHRHR) in a cohort of isolated growth hormone deficient (IGHD) children in Sri Lanka.
Sundralingam T et al.·Growth Horm IGF Res
2017Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools