LHB

luteinizing hormone subunit beta, the group of Receptor ligands|Glycoprotein hormone subunits

Basic information

Region (hg38): 19:49015980-49017091

Links

ENSG00000104826 ∙ NCBI:3972 ∙ OMIM:152780 ∙ HGNC:6584 ∙ Uniprot:P01229 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypogonadotropic hypogonadism 23 with or without anosmia (Strong), mode of inheritance: AR
• hypogonadotropic hypogonadism 23 with or without anosmia (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypogonadotropic hypogonadism 23 with or without anosmia	AR	Endocrine	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	Endocrine	429481; 1727547; 7904610; 7714098; 9457942; 15602022; 19129711; 19890128; 22723313

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LHB gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LHB gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6	6	12
missense			16	8	5	29
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding				10	8	18
Total	0	0	17	24	19

Variants in LHB

This is a list of pathogenic ClinVar variants found in the LHB region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-49015983-G-A			Benign (Nov 08, 2018)
19-49016079-G-A			Benign (Aug 24, 2023)
19-49016121-C-T		not specified	Uncertain significance (Sep 17, 2021)
19-49016130-C-T		Variant of unknown significance • Isolated lutropin deficiency	Likely benign (Nov 27, 2023)
19-49016142-A-T		not specified	Uncertain significance (Jul 27, 2024)
19-49016155-G-A			Likely benign (Feb 05, 2024)
19-49016162-C-G		not specified	Uncertain significance (Jul 27, 2024)
19-49016168-C-T		not specified	Likely benign (Feb 27, 2023)
19-49016187-G-C		not specified	Uncertain significance (Jul 27, 2024)
19-49016199-C-T		not specified	Likely benign (Jan 11, 2023)
19-49016208-C-T		Isolated lutropin deficiency	Uncertain significance (Mar 08, 2020)
19-49016209-A-G		Isolated lutropin deficiency	Benign (Jan 31, 2024)
19-49016216-G-A		not specified	Likely benign (Mar 19, 2024)
19-49016216-G-C		not specified	Uncertain significance (Apr 08, 2022)
19-49016232-G-A			Likely benign (Jul 03, 2023)
19-49016248-C-T			Likely benign (Sep 26, 2021)
19-49016254-A-G		LHB-related disorder	Benign (Dec 13, 2023)
19-49016261-G-T		Isolated lutropin deficiency	Benign/Likely benign (Jan 15, 2024)
19-49016263-G-A		LHB-related disorder	Benign (Jan 18, 2024)
19-49016273-T-C		Isolated lutropin deficiency	Pathogenic (Jan 16, 1992)
19-49016282-G-A		not specified	Uncertain significance (May 24, 2024)
19-49016283-G-C		not specified	Uncertain significance (Jul 26, 2021)
19-49016284-C-T			Likely benign (Mar 01, 2023)
19-49016294-G-C			Benign (Jan 13, 2024)
19-49016305-G-A			Likely benign (Dec 26, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LHB	protein_coding	protein_coding	ENST00000221421	3	1102

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00225	0.542	125625	0	7	125632	0.0000279

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.623	108	91.3	1.18	0.00000660	886
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.0000468	0.0000462
European (Non-Finnish)	0.0000265	0.0000264
Middle Eastern	0.0000545	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Promotes spermatogenesis and ovulation by stimulating the testes and ovaries to synthesize steroids.
• Pathway: 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;T-Cell antigen Receptor (TCR) Signaling Pathway;Signaling by GPCR;Signal Transduction;Peptide hormone metabolism;Metabolism of lipids;Post-translational protein modification;Reactions specific to the complex N-glycan synthesis pathway;N-glycan antennae elongation in the medial/trans-Golgi;Metabolism of proteins;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Metabolism;G alpha (s) signalling events;Mineralocorticoid biosynthesis;Hormone ligand-binding receptors;Androgen biosynthesis;Metabolism of steroid hormones;Metabolism of steroids;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;GPCR signaling-G alpha i;Glycoprotein hormones;GPCR downstream signalling;Steroid hormones;Peptide hormone biosynthesis (Consensus)

Recessive Scores

• pRec: 0.477

Intolerance Scores

• loftool: 0.375
• rvis_EVS: 0.75
• rvis_percentile_EVS: 86.65

Haploinsufficiency Scores

• pHI: 0.168
• hipred: N
• hipred_score: 0.112
• ghis: 0.421

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.141

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lhb
• Phenotype: reproductive system phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: lhb
• Affected structure: postovulatory follicle
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: progesterone biosynthetic process;signal transduction;G protein-coupled receptor signaling pathway;cell-cell signaling;male gonad development;hormone-mediated signaling pathway;regulation of signaling receptor activity;peptide hormone processing
• Cellular component: extracellular region;extracellular space;cytoplasm;Golgi lumen
• Molecular function: signaling receptor binding;hormone activity