LBX1

protein-coding

ladybird homeobox 1, the group of NKL subclass homeoboxes and pseudogenes

Gene summary

This gene and the orthologous mouse gene were found by their homology to the Drosophila lady bird early and late homeobox genes. In the mouse, this gene is a key regulator of muscle precursor cell migration and is required for the acquisition of dorsal identities of forelimb muscles. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006562.5

Inheritance

ClinVar variants

P:1U:26B:2

Top phenotype

Central hypoventilation syndrome, congenital 3

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr10:101,226,994-101,229,463

External References & Databases

Ensembl (ENSG00000138136)

Transcript & Mutation Effects

hg38 • Region Span ~2.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

central hypoventilation syndrome, congenital, 3MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0030539

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Central hypoventilation syndrome, congenital 3AR

Manifestation: Gastrointestinal; Neurologic

Intervention: Neurologic

Rationale: In Central hypoventilation syndrome, congenital, early recognition and interventions to support ventilation may reduce morbidity and mortality

Refs: 30487221

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LBX1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 25

not providedTotal: 5

Central hypoventilation syndrome, congenital, 3Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006562.5. 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 clinvar	1
missense			26 clinvar	1 clinvar		27
nonsense						0
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)						0
Total	0	1	26	1	1	29

Highest pathogenic variant AF is 0.0000013816143

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006562.5	RefSeq	NP_006553.2	2	MANE Select
ENST00000370193.4	Ensembl	ENSP00000359212.2	2	MANE Select
ENST00000945825.1	Ensembl	ENSP00000615884.1	2	Standard
ENST00000945826.1	Ensembl	ENSP00000615885.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

heart looping
muscle organ development
negative regulation of cell population proliferation
anatomical structure morphogenesis
spinal cord motor neuron differentiation

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
sequence-specific DNA binding

Cellular Component

nucleus
transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370193
Coding exons: 2
Length: 2819
Individuals with no LoFs: 118177
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 118178
p: 0.00000423

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.11	121	161	0.753	0.00000728	1763
Missense (PolyPhen)		29	63.395	0.45745		666
Synonymous	0.0602	77	77.7	0.991	0.00000364	595
Loss of Function	2.29	1	8.00	0.125	3.41e-7	90

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0.00017	0.00017	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription factor required for the development of GABAergic interneurons in the dorsal horn of the spinal cord and migration and further development of hypaxial muscle precursor cells for limb muscles, diaphragm and hypoglossal cord. {ECO:0000250}.;

Recessive Scores

pRec: 0.268

Intolerance Scores

RVIS EVS: -0.3
RVIS percentile EVS: 32.62

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.225

Gene Damage Prediction

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