LMX1A

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

Basic information

Region (hg38): 1:165201867-165356715

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
autosomal dominant nonsyndromic hearing loss 7 (Limited), mode of inheritance: AD
hearing loss, autosomal recessive (Limited), mode of inheritance: AR
Mobius syndrome (Limited), 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_specified (38 variants)
not_provided (15 variants)
LMX1A-related_disorder (15 variants)
Autosomal_dominant_nonsyndromic_hearing_loss_7 (14 variants)
Schizophrenia (1 variants)
Autosomal-Recessive_Hereditary_Hearing_Impairment (1 variants)
Sensorineural_hearing_loss_disorder (1 variants)
Monogenic_hearing_loss (1 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. These statistics are base on transcript: NM_000177398.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	3 clinvar	3 clinvar	7
missense	3 clinvar	2 clinvar	48 clinvar	3 clinvar		56
nonsense	1 clinvar	2 clinvar	1 clinvar			4
start loss						0
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	4	5	51	6	3

Highest pathogenic variant AF is 0.00001177166

Loading clinvar variants...

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