LMX1B

LIM homeobox transcription factor 1 beta, the group of LIM class homeoboxes

Basic information

Region (hg38): 9:126613927-126701032

Previous symbols: [ "NPS1" ]

Links

ENSG00000136944 ∙ NCBI:4010 ∙ OMIM:602575 ∙ HGNC:6654 ∙ Uniprot:O60663 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nail-patella syndrome (Supportive), mode of inheritance: AD
• nail-patella-like renal disease (Supportive), mode of inheritance: AD
• nail-patella syndrome (Strong), mode of inheritance: AD
• nail-patella syndrome (Definitive), mode of inheritance: AD
• nail-patella syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nail-patella syndrome; Focal segmental glomerulosclerosis 10	AD	Ophthalmologic; Pharmacogenomic; Renal	In Nail-patella syndrome, individuals may have open-angle glaucoma, and surveillance and appropriate treatment may be beneficial; Agents that may contribute to glaucoma (as well as NSAIDs as relates to renal function) should be avoided; Medical treatment (eg, ACE inhibitors) may be beneficial in terms of affecting the progression of renal disease; Renal transplantation has been described; In Focal segmental glomerulosclerosis, recognition of disease may allow early management, and renal transplant has been described	Dermatologic; Musculoskeletal; Ophthalmologic; Renal	9590287; 9618165; 15928687; 17515884; 18414507; 20301311; 21850167; 23687361; 32356190; 32791958
Onset may typically be during adulthood, though surveillance earlier may be warranted given reports of affected individuals in the 3rd decade

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LMX1B gene.

• not provided (305 variants)
• Nail-patella syndrome (234 variants)
• Nail-patella syndrome;Nail-patella-like renal disease (28 variants)
• Inborn genetic diseases (22 variants)
• not specified (15 variants)
• LMX1B-related condition (8 variants)
• Nail-patella-like renal disease (5 variants)
• Focal segmental glomerulosclerosis (4 variants)
• Kidney disorder (2 variants)
• Nail-patella-like renal disease;Nail-patella syndrome (2 variants)
• Nephrotic syndrome (1 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LMX1B 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			4	58	4	66
missense	11	15	90	8		124
nonsense	28					28
start loss						0
frameshift	20	3				23
inframe indel	3		1			4
splice donor/acceptor (+/-2bp)	9	2				11
splice region			7	8	1	16
non coding			96	44	77	217
Total	71	20	191	110	81

Highest pathogenic variant AF is 0.00000657

Variants in LMX1B

This is a list of pathogenic ClinVar variants found in the LMX1B region.

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

Position	Type	Phenotype	Significance	ClinVar
9-126614438-G-T		Nail-patella syndrome	Uncertain significance (Jan 13, 2018)
9-126614468-C-G		Nail-patella syndrome	Likely benign (Dec 23, 2023)
9-126614469-C-G		Inborn genetic diseases	Uncertain significance (Oct 30, 2023)
9-126614471-G-A		Inborn genetic diseases	Uncertain significance (Apr 10, 2023)
9-126614485-G-T			Uncertain significance (Sep 13, 2022)
9-126614491-C-T			Likely benign (Feb 08, 2023)
9-126614500-G-A			Likely benign (Jul 12, 2023)
9-126614506-G-A		Nail-patella syndrome	Conflicting classifications of pathogenicity (Jun 06, 2023)
9-126614507-G-A		LMX1B-related disorder	Uncertain significance (Sep 19, 2023)
9-126614509-C-T			Likely benign (Aug 13, 2022)
9-126614513-G-A			Uncertain significance (Nov 13, 2023)
9-126614531-A-G			Uncertain significance (Sep 20, 2023)
9-126614543-G-A		Nail-patella syndrome	Uncertain significance (Jan 13, 2018)
9-126614548-C-T			Likely benign (Sep 17, 2021)
9-126614552-C-T			Likely benign (Jan 22, 2024)
9-126614558-C-T			Uncertain significance (Nov 27, 2023)
9-126614564-C-G		Inborn genetic diseases	Uncertain significance (Jul 20, 2021)
9-126614564-C-T		Nail-patella syndrome • Inborn genetic diseases	Uncertain significance (Jun 22, 2023)
9-126614574-T-TG			Pathogenic (Apr 17, 2023)
9-126614579-G-A		Nail-patella syndrome;Nail-patella-like renal disease	Uncertain significance (Jan 25, 2024)
9-126614593-G-C		Nail-patella syndrome	Uncertain significance (Jan 01, 2023)
9-126614607-C-T		not specified • Nail-patella syndrome;Nail-patella-like renal disease	Benign/Likely benign (Dec 09, 2023)
9-126614797-C-T			Benign (Nov 10, 2018)
9-126614883-G-A			Benign (Jul 07, 2018)
9-126615117-A-G			Benign (Aug 20, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LMX1B	protein_coding	protein_coding	ENST00000355497	8	86590

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.746	0.254	125704	0	3	125707	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.02	169	261	0.648	0.0000168	2624
Missense in Polyphen		43	99.872	0.43055		1013
Synonymous	-0.810	128	117	1.10	0.00000854	759
Loss of Function	3.56	4	22.1	0.181	0.00000120	214

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000882	0.0000882
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential for the specification of dorsal limb fate at both the zeugopodal and autopodal levels.
• Pathway: Primary Focal Segmental Glomerulosclerosis FSGS;Dopaminergic Neurogenesis;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways (Consensus)

Recessive Scores

• pRec: 0.350

Intolerance Scores

• loftool: 0.0982
• rvis_EVS: -0.85
• rvis_percentile_EVS: 11.06

Haploinsufficiency Scores

• pHI: 0.358
• hipred: Y
• hipred_score: 0.837
• ghis: 0.501

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.980

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lmx1b
• Phenotype: taste/olfaction phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); craniofacial phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; renal/urinary system phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: lmx1ba
• Affected structure: glutamatergic neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: in utero embryonic development;regulation of transcription, DNA-templated;multicellular organism development;dorsal/ventral pattern formation;neuron differentiation;positive regulation of transcription by RNA polymerase II;dopaminergic neuron differentiation
• Cellular component: nucleus
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;metal ion binding