LHB
protein-codingluteinizing hormone subunit beta, the group of Receptor ligands|Glycoprotein hormone subunits
Gene summary
This gene is a member of the glycoprotein hormone beta chain family and encodes the beta subunit of luteinizing hormone (LH). Glycoprotein hormones are heterodimers consisting of a common alpha subunit and an unique beta subunit which confers biological specificity. LH is expressed in the pituitary gland and promotes spermatogenesis and ovulation by stimulating the testes and ovaries to synthesize steroids. The genes for the beta chains of chorionic gonadotropin and for luteinizing hormone are contiguous on chromosome 19q13.3. Mutations in this gene are associated with hypogonadism which is characterized by infertility and pseudohermaphroditism. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009223
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0009223
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0009223
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Endocrine
Intervention: Endocrine
Rationale: Homozygous/compound heterozygous males may not undergo spontaneous puberty, and treatment (eg, with HCG) can be beneficial; Females may be affected with infertility and oligo-amenorrhea, and medical treatment (eg, with HCG) may be beneficial; Monitoring of bone mineral density may be beneficial in order to allow early detection and treatment of disease
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LHB variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000894.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 12 | 1 | 14 | ||
| missense | 2 | 32 | 9 | 2 | 45 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 4 | 0 | 34 | 21 | 3 | 62 |
Highest pathogenic variant AF is 0.000006851455
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000885.1 | 3 | MANE Select | |
| Ensembl | ENSP00000497294.2 | 3 | MANE Select | |
| RefSeq | XP_047294788.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| lhb | Danio rerio | Structure: postovulatory follicle Quality: absent abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- GnRH signaling pathway - Homo sapiens (human)
- Prolactin signaling pathway - Homo sapiens (human)
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- Ovarian steroidogenesis - Homo sapiens (human)
- Intracellular Signalling Through LHCGR Receptor and Luteinizing Hormone/Choriogonadotropin
Biological Process
- progesterone biosynthetic process
- signal transduction
- G protein-coupled receptor signaling pathway
- cell-cell signaling
- male gonad development
Molecular Function
- signaling receptor binding
- hormone activity
Cellular Component
- extracellular region
- extracellular space
- cytoplasm
- Golgi lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000221421
- Coding exons
- 3
- Length
- 1102
- Individuals with no LoFs
- 125625
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125632
- p
- 0.0000279
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.623 | 108 | 91.3 | 1.18 | 0.00000660 | 886 |
| Missense (PolyPhen) | 37 | 39.08 | 0.94679 | 404 | ||
| Synonymous | -1.03 | 47 | 38.8 | 1.21 | 0.00000270 | 312 |
| Loss of Function | 0.228 | 4 | 4.52 | 0.884 | 1.95e-7 | 48 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Promotes spermatogenesis and ovulation by stimulating the testes and ovaries to synthesize steroids.;
Recessive Scores
- pRec
- 0.477
Intolerance Scores
- LoFtool
- 0.375
- RVIS EVS
- 0.75
- RVIS percentile EVS
- 86.65
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.141
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |