LMX1A

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

Basic information

Region (hg38): 1:165201866-165356715

Previous symbols: [ "LMX1" ]

Links

ENSG00000162761 ∙ NCBI:4009 ∙ OMIM:600298 ∙ HGNC:6653 ∙ Uniprot:Q8TE12 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss 7 (Strong), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 7 (Limited), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 7 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 7	AD	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	29754270

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LMX1A gene.

• not provided (21 variants)
• Inborn genetic diseases (11 variants)
• Autosomal dominant nonsyndromic hearing loss 7 (9 variants)
• LMX1A-related condition (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LMX1A 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				1	5	6
missense	1		17			18
nonsense	1	2				3
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					14	14
Total	2	3	17	1	19

Highest pathogenic variant AF is 0.00000657

Variants in LMX1A

This is a list of pathogenic ClinVar variants found in the LMX1A region.

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

Position	Type	Phenotype	Significance	ClinVar
1-165203923-A-G		Sensorineural hearing loss disorder • Autosomal-Recessive Hereditary Hearing Impairment	Conflicting classifications of pathogenicity (Feb 12, 2020)
1-165203936-C-T		not specified	Uncertain significance (Aug 12, 2021)
1-165203969-C-T		not specified	Uncertain significance (May 05, 2023)
1-165203979-A-G		Autosomal dominant nonsyndromic hearing loss 7	Benign (Aug 19, 2021)
1-165204004-T-C		not specified	Uncertain significance (May 15, 2023)
1-165204008-C-G		not specified	Uncertain significance (Mar 02, 2023)
1-165204035-C-T		not specified	Uncertain significance (Mar 20, 2023)
1-165205722-C-T			Benign (May 13, 2021)
1-165205901-G-A		LMX1A-related disorder	Benign (May 20, 2019)
1-165205914-C-T		LMX1A-related disorder	Uncertain significance (Sep 28, 2022)
1-165205915-G-A		Autosomal dominant nonsyndromic hearing loss 7	Likely pathogenic (May 31, 2023)
1-165205954-G-T		not specified	Uncertain significance (Aug 02, 2021)
1-165205969-T-G		LMX1A-related disorder	Likely benign (Jul 21, 2022)
1-165205978-C-T		Autosomal dominant nonsyndromic hearing loss 7	Uncertain significance (Aug 24, 2022)
1-165205980-G-A		not specified	Uncertain significance (Sep 06, 2022)
1-165206003-C-T		not specified	Uncertain significance (Dec 18, 2023)
1-165206034-G-A		not specified	Uncertain significance (Jan 17, 2024)
1-165206137-G-A			Benign (May 12, 2021)
1-165207933-T-C			Benign (May 12, 2021)
1-165208094-T-TTGC		LMX1A-related disorder	Likely benign (May 03, 2023)
1-165208114-G-A			Likely pathogenic (Feb 22, 2023)
1-165210637-C-A			Benign (May 14, 2021)
1-165210694-G-A		LMX1A-related disorder	Likely benign (Jan 01, 2024)
1-165210702-C-T		LMX1A-related disorder	Likely benign (May 13, 2019)
1-165210725-C-G		Autosomal dominant nonsyndromic hearing loss 7	Pathogenic (Feb 12, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LMX1A	protein_coding	protein_coding	ENST00000342310	8	154849

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.991	0.00886	125725	0	6	125731	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.00	175	216	0.808	0.0000114	2500
Missense in Polyphen		56	91.757	0.61031		1036
Synonymous	0.565	82	88.8	0.924	0.00000482	725
Loss of Function	4.06	2	23.0	0.0870	0.00000132	232

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a transcriptional activator by binding to an A/T-rich sequence, the FLAT element, in the insulin gene promoter. Required for development of the roof plate and, in turn, for specification of dorsal cell fates in the CNS and developing vertebrae (By similarity). {ECO:0000250}.
• Pathway: Dopaminergic Neurogenesis (Consensus)

Recessive Scores

• pRec: 0.230

Intolerance Scores

• loftool: 0.0623
• rvis_EVS: -0.74
• rvis_percentile_EVS: 13.94

Haploinsufficiency Scores

• pHI: 0.370
• hipred: Y
• hipred_score: 0.699
• ghis: 0.510

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.986

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lmx1a
• 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); growth/size/body region phenotype; taste/olfaction phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial 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); reproductive system phenotype; pigmentation phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton 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); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype

Gene ontology

• Biological process: regulation of cell growth;axon guidance;memory;locomotory behavior;dentate gyrus development;cerebellum development;olfactory behavior;negative regulation of neuron differentiation;positive regulation of transcription by RNA polymerase II;synapse organization;dopaminergic neuron differentiation;midbrain 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 activator activity, RNA polymerase II-specific;protein binding;metal ion binding