LMX1B

Summary

LMX1B (LIM homeobox transcription factor 1 beta, HGNC:6654) is a protein-coding gene on chromosome 9q33.3, encoding LIM homeobox transcription factor 1-beta (O60663). Transcription factor involved in the regulation of podocyte-expressed genes. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of LIM-homeodomain family of proteins containing two N-terminal zinc-binding LIM domains, 1 homeodomain, and a C-terminal glutamine-rich domain. It functions as a transcription factor, and is essential for the normal development of dorsal limb structures, the glomerular basement membrane, the anterior segment of the eye, and dopaminergic and serotonergic neurons. Mutations in this gene are associated with nail-patella syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4010 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nail-patella syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 49
• Clinical variants (ClinVar): 715 total — 119 pathogenic, 33 likely-pathogenic
• Phenotypes (HPO): 155
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 27 downstream targets (CollecTRI)
• MANE Select transcript: NM_001174147

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6654
Approved symbol	LMX1B
Name	LIM homeobox transcription factor 1 beta
Location	9q33.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000136944
Ensembl biotype	protein_coding
OMIM	602575
Entrez	4010

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000355497, ENST00000373474, ENST00000526117

RefSeq mRNA: 3 — MANE Select: NM_001174147 NM_001174146, NM_001174147, NM_002316

CCDS: CCDS55342, CCDS55343, CCDS6866

Canonical transcript exons

ENST00000373474 — 8 exons

Exon	Start	End
ENSE00000927112	126615383	126615569
ENSE00000927113	126690836	126691068
ENSE00000927114	126693142	126693323
ENSE00000927115	126693524	126693601
ENSE00000927116	126693746	126693812
ENSE00001381436	126695839	126696003
ENSE00003900933	126696294	126701032
ENSE00003901704	126613928	126614588

Expression profiles

Bgee: expression breadth broad, 74 present calls, max score 81.61.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9909 / max 66.9851, expressed in 384 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98556	1.6425	343
98557	1.2787	260
98558	0.0697	44

Top tissues by expression

225 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	81.61	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.12	gold quality
buccal mucosa cell	CL:0002336	69.84	gold quality
parotid gland	UBERON:0001831	67.69	gold quality
skin of leg	UBERON:0001511	61.67	gold quality
right atrium auricular region	UBERON:0006631	60.48	gold quality
adult mammalian kidney	UBERON:0000082	60.27	gold quality
cardiac atrium	UBERON:0002081	59.96	gold quality
skin of abdomen	UBERON:0001416	59.52	gold quality
apex of heart	UBERON:0002098	59.18	gold quality
medial globus pallidus	UBERON:0002477	58.42	gold quality
zone of skin	UBERON:0000014	58.30	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	57.77	gold quality
myocardium	UBERON:0002349	57.42	gold quality
tendon of biceps brachii	UBERON:0008188	56.36	gold quality
cartilage tissue	UBERON:0002418	55.90	gold quality
substantia nigra	UBERON:0002038	55.80	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	55.48	gold quality
hindlimb stylopod muscle	UBERON:0004252	55.03	gold quality
kidney	UBERON:0002113	54.89	gold quality
heart right ventricle	UBERON:0002080	54.81	gold quality
globus pallidus	UBERON:0001875	54.53	gold quality
trabecular bone tissue	UBERON:0002483	54.19	gold quality
midbrain	UBERON:0001891	53.99	gold quality
mucosa of sigmoid colon	UBERON:0004993	53.85	gold quality
heart	UBERON:0000948	53.30	gold quality
saliva-secreting gland	UBERON:0001044	52.81	gold quality
postcentral gyrus	UBERON:0002581	52.13	gold quality
heart left ventricle	UBERON:0002084	51.48	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.25

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

27 targets.

Target	Regulation
CASP3
CD2AP	Unknown
CDKN1B
COL3A1	Unknown
COL4A1	Unknown
COL4A3	Unknown
COL4A4	Activation
CXCL8	Activation
EBF1
FGF8	Unknown
FN1
GAD1
HES1
HESX1	Activation
IL6	Activation
LDB1
LMX1A	Activation
LMX1B
NLRP2	Activation
NPHS2	Unknown
NR4A2	Activation
PITX3	Activation
SLC17A6
TCF3	Activation
WNT1	Activation
WNT7A
ZIC1	Repression

JASPAR motifs

Motif	Name	Family
MA0703.1	LMX1B	HD-LIM
MA0703.2	LMX1B	HD-LIM
MA0703.3	LMX1B	HD-LIM

JASPAR matrix evidence (PMIDs): PMID:18585360, PMID:18585359

Upstream regulators (CollecTRI, top): FOXA1, FOXA2, LMX1A, LMX1B, MYC, NKX2-2, SOX3

miRNA regulators (miRDB)

159 targeting LMX1B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6892-3P	99.68	66.40	1178

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• novel mutations in patients with nail patella syndrome (PMID:11668639)
• Transcriptional induction of slit diaphragm genes by Lmx1b is required in podocyte differentiation. (PMID:11956244)
• The LIM-homeodomain transcription factor Lmx1b plays a crucial role in podocytes (PMID:11956245)
• Review. Lmx1b is a homeodomain transcription factor required for glomerular basement membrane collagen expression by podocytes. Its absence in nail-patella syndrome causes abnormalities in many organ systems. (PMID:11978876)
• LMX1B 17-bp deletion and A3243G mtDNA transition in a previously described (PMID:12646768)
• These findings indicate that heterozygous mutations of LMX1B do not appear to dramatically affect the expression of type IV collagen chains, podocin, or CD2AP in nail-patella syndrome patients. (PMID:12819019)
• Single nucleotide polymorphisms in LMX1B gene is associated with nail dysplasia in the nail patella syndrome (PMID:15638822)
• This is the first study indicating that family history of nephropathy and mutation location might be important in precipitating individual risks for developing NPS renal disease (PMID:15928687)
• Pathogenic mechanism resulting from the mutation is presumably haploinsufficiency rather than a dominant negative effect, which would explain the clinical variability in this family. (PMID:17515884)
• familial Mediterranean fever (FMF) heterozygote mutation and nail-patella syndrome (NPS) in 3 members of a family with no pathologic mutation in the LMX1B gene (PMID:17710881)
• The detection of two entire LMX1B gene deletions and one smaller exonic LMX1B deletion by multiplex ligation-dependent probe amplification (MLPA), is described. (PMID:18414507)
• study reports a novel LMX1B gene mutation c.368_369delTG, p.C123X in a Japanese girl with the typical nail changes of nail-patella syndrome; the proband’s father carried the same mutation, although his fingernails were intact (PMID:18562181)
• a mutation in the LMX1B gene causes nail-patella syndrome in a Chinese population (PMID:18595794)
• Familial, genetic proved ((missense mutation -G599A (R200Q)of LMX1B gene))of nail patella syndrome in a mother and her son (PMID:18634531)
• LMX1B haplotypes influence susceptibility to glaucoma in the general population, suggesting altered LMX1B function predisposes to glaucomatous damage and that this role may be independent of raised intraocular pressure. (PMID:18952915)
• These data demonstrate for the first time that LMX1B directly regulates transcription of a subset of NF-kappaB target genes in cooperation with nuclear p50/p65 NF-kappaB. (PMID:18996370)
• Data show that three single nucleotide polymor in LMX1A and one in LMX1B are associated with Parkinson’s disease. (PMID:19189040)
• podocin is specifically regulated by the transcription factor Lmx1b and by the functional polymorphism -116C/T. (PMID:19562271)
• A synonymous genetic alteration of LMX1B in a family with nail-patella syndrome. (PMID:19721866)
• LMX1B mutations is associated with Nail-Patella syndrome. (PMID:20531206)
• Genetic variation in LMX1B may increase the risk of developing schizophrenia. (PMID:20570600)
• The co-occurrence of nail-patella syndrome, attention deficit hyperactivity disorder and major depressive disorder may be related to mesencephalic dopaminergic neurologic pathway abnormalities that are a consequence of LMX1B loss of function. (PMID:21184584)
• effect of lmx1b on gene expression regulation in the brain (PMID:21246047)
• c.194 A>C (Q65P) mutation is present in the LMX1B gene of the Chilean patients with nail-patella syndrome associated with glaucoma. (PMID:21850167)
• Data report on the association of LMX1B with autism, though it should be viewed with some caution considering the modest associations we report. (PMID:21901133)
• LMX1B is important in regulating type IV collagen gene expression in the GBM of the developing kidney and also has a likely role in regulating additional genes important in podocyte function and maintenance (PMID:23046462)
• this study identified two novel mutations of the LMX1B gene in three unrelated families with autosomaldominant Focal Segmental Glomerulosclerosis and no extrarenal features. (PMID:23687361)
• LMX1B is a novel oncogene in ovarian cancer pathogenesis. (PMID:24056967)
• In a large family with the two disorders with two novel frameshift TSC1 and LMX1B mutations, we describe the phenotypes (PMID:24477276)
• Results demonstrate that loss of function may not be the only way that mutated LMX1b causes haploinsufficiency. Mutated LMX1b may interfere withdownsteam transcription events. (PMID:24720768)
• A heterozygous microdeletion of the entire LMX1B gene using multiplex ligation-dependent probe amplification (MLPA) in a Chinese family with nail patella syndrome, is reported. (PMID:25380522)
• 38 different LMX1B polymorphisms have been found in 55 families with Nail-Patella Syndrome raising the hypothesis of a genetic heterogeneity. (PMID:25898926)
• these results reveal a sustained and essential requirement of Lmx1b for the function of midbrain dopamine neurons (PMID:25915474)
• 9q33.3q34.11 microdeletion including LMX1b gene identified in four patients with intellectual disability, epilepsy, nail dysplasia and bone malformations. (PMID:26395556)
• Lmx1a and Lmx1b expression persists in mature dopaminergic neurons of the substantia nigra pars compacta and the ventral tegmental area. [Review] (PMID:26526610)
• Report progression of autosomal dominant renal-limited disease with LMX1B mutation. (PMID:26560070)
• Study reports two additional families with 18 affected individuals with nail patella-like renal disease (NPLRD). The predominant LMX1B mutation is the previously reported R246Q mutation. (PMID:28059119)
• Study identified a novel heterozygous in-frame indel mutation of LMX1B in a family of Nail patella syndrome. (PMID:29290531)
• Upregulated LMX1B mRNA expression had an independent prognostic value in LSCC patients. (PMID:31387183)
• LMX1B is a key regulator involved in the radioresistance of Esophagela cancer. (PMID:31545286)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lmx1bb	ENSDARG00000068365
danio_rerio	lmx1ba	ENSDARG00000104815
mus_musculus	Lmx1b	ENSMUSG00000038765
rattus_norvegicus	Lmx1b	ENSRNOG00000017019

Paralogs (20): FHL1 (ENSG00000022267), LMO3 (ENSG00000048540), LHX5 (ENSG00000089116), ZFHX4 (ENSG00000091656), LHX2 (ENSG00000106689), LHX6 (ENSG00000106852), LHX3 (ENSG00000107187), LHX4 (ENSG00000121454), LMO2 (ENSG00000135363), ZFHX2 (ENSG00000136367), ZFHX3 (ENSG00000140836), LMO4 (ENSG00000143013), LHX9 (ENSG00000143355), CRIP3 (ENSG00000146215), LHX8 (ENSG00000162624), LMX1A (ENSG00000162761), LMO1 (ENSG00000166407), CRIP2 (ENSG00000182809), CRIP1 (ENSG00000213145), LHX1 (ENSG00000273706)

Protein

Protein identifiers

LIM homeobox transcription factor 1-beta — O60663 (reviewed: O60663)

Alternative names: LIM/homeobox protein 1.2, LIM/homeobox protein LMX1B

All UniProt accessions (1): O60663

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor involved in the regulation of podocyte-expressed genes. Essential for the specification of dorsal limb fate at both the zeugopodal and autopodal levels.

Subunit / interactions. Interacts with DHX9.

Subcellular location. Nucleus.

Tissue specificity. Expressed in most tissues. Highest levels in testis, thyroid, duodenum, skeletal muscle, and pancreatic islets.

Disease relevance. Nail-patella syndrome (NPS) [MIM:161200] Disease that cause abnormal skeletal patterning and renal dysplasia. The disease is caused by variants affecting the gene represented in this entry. Focal segmental glomerulosclerosis 10 (FSGS10) [MIM:256020] An autosomal dominant form of focal segmental glomerulosclerosis, a renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
O60663-1	1, Long	yes
O60663-2	2, Short
O60663-3	3

RefSeq proteins (3): NP_001167617, NP_001167618, NP_002307 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR001781	Znf_LIM	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR050453	LIM_Homeobox_TF	Family

Pfam: PF00046, PF00412

UniProt features (43 total): sequence variant 33, domain 2, region of interest 2, splice variant 2, chain 1, DNA-binding region 1, mutagenesis site 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60663-F1	70.79	0.31

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (1):

Position	Phenotype
265	loss of transcriptional activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 426 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_NEUROGENESIS, GGGTGGRR_PAX4_03, GOBP_DORSAL_VENTRAL_PATTERN_FORMATION, COUP_01, HNF4_01, TGACATY_UNKNOWN, RYTTCCTG_ETS2_B, GOBP_DOPAMINERGIC_NEURON_DIFFERENTIATION, CUI_TCF21_TARGETS_2_DN, DANG_BOUND_BY_MYC, E2F1_Q3_01, YKACATTT_UNKNOWN, HNF4ALPHA_Q6, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING

GO Biological Process (6): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), dorsal/ventral pattern formation (GO:0009953), neuron differentiation (GO:0030182), positive regulation of transcription by RNA polymerase II (GO:0045944), dopaminergic neuron differentiation (GO:0071542)

GO Molecular Function (8): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription factor activity (GO:0003700), metal ion binding (GO:0046872), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
transcription cis-regulatory region binding	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regionalization	1
cell differentiation	1
generation of neurons	1
positive regulation of DNA-templated transcription	1
neuron differentiation	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
transcription regulator activity	1
cation binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
DNA binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1422 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LMX1B	NKX2-2	O95096	895
LMX1B	PAX2	Q02962	821
LMX1B	LDB1	Q86U70	804
LMX1B	ASCL1	P50553	792
LMX1B	NPHS2	Q9NP85	772
LMX1B	SHH	Q15465	756
LMX1B	LDB2	O43679	740
LMX1B	AK1	P00568	739
LMX1B	GPR107	Q5VW38	726
LMX1B	NR4A2	P43354	718
LMX1B	NPHS1	O60500	717
LMX1B	COL4A4	P53420	704
LMX1B	WNT7A	O00755	701
LMX1B	MYT1L	Q9UL68	688
LMX1B	MYOC	Q99972	682

IntAct

22 interactions, top by confidence:

A	B	Type	Score
LMX1B	LDB1	psi-mi:“MI:0915”(physical association)	0.750
LDB1	LMX1B	psi-mi:“MI:0915”(physical association)	0.750
LMX1B	SSBP3	psi-mi:“MI:0915”(physical association)	0.740
SSBP3	LMX1B	psi-mi:“MI:0914”(association)	0.740
SSBP4	LDB2	psi-mi:“MI:0914”(association)	0.550
SSBP2	CLEC18A	psi-mi:“MI:0914”(association)	0.530
SSBP4	LMX1B	psi-mi:“MI:0914”(association)	0.530
CDC37	LMX1B	psi-mi:“MI:0915”(physical association)	0.400
CFTR	LMX1B	psi-mi:“MI:0915”(physical association)	0.370
SSBP3	LHX2	psi-mi:“MI:0914”(association)	0.350
LMX1B	POTEF	psi-mi:“MI:0914”(association)	0.350
ISL2	BCL9	psi-mi:“MI:0914”(association)	0.350
MFAP4	PEX1	psi-mi:“MI:0914”(association)	0.350
RBSN	LMX1B	psi-mi:“MI:0914”(association)	0.350
IDI2	LMX1B	psi-mi:“MI:0914”(association)	0.350
LMO2	POLR2D	psi-mi:“MI:0914”(association)	0.350
ISL2	LMX1B	psi-mi:“MI:0914”(association)	0.350
LHX6	LMX1B	psi-mi:“MI:0914”(association)	0.350
LMO3	LMX1B	psi-mi:“MI:0914”(association)	0.350
LMO1	LMX1B	psi-mi:“MI:0914”(association)	0.350
LMX1B	CD33	psi-mi:“MI:0914”(association)	0.350

BioGRID (70): LDB1 (Two-hybrid), MAB21L1 (Affinity Capture-MS), POTEF (Affinity Capture-MS), ACTB (Affinity Capture-MS), PKNOX2 (Affinity Capture-MS), PARS2 (Affinity Capture-MS), LDB1 (Affinity Capture-MS), PBX1 (Affinity Capture-MS), PBX2 (Affinity Capture-MS), PBX3 (Affinity Capture-MS), MEIS1 (Affinity Capture-MS), MEIS2 (Affinity Capture-MS), SSBP2 (Affinity Capture-MS), SSBP4 (Affinity Capture-MS), SSBP3 (Affinity Capture-MS)

ESM2 similar proteins: A5PMU4, O60663, O75541, O88609, O97581, P29674, P36200, P48742, P50211, P50212, P50480, P50481, P52889, P53405, P53406, P53407, P53408, P53409, P53410, P53411, P53412, P53413, P53776, P61371, P61372, P61373, P61374, P61375, P61376, P63006, P63007, P63008, Q04650, Q32KS7, Q5IS44, Q5IS89, Q60564, Q6H8Q1, Q6KC51, Q6PD05

Diamond homologs: A0JNI8, A2I8Z7, A2PZF9, G5EC36, G5EE86, O14639, O35652, O60663, O88609, O94929, O97581, P20154, P25791, P25800, P25801, P29673, P29674, P34764, P34765, P36198, P36200, P37137, P48742, P50211, P50212, P50458, P50480, P50481, P52889, P53405, P53406, P53407, P53408, P53409, P53410, P53411, P53412, P53413, P53667, P53668

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
LMX1B	“form complex”	“LMX1B/SFPQ/PSPC1 complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

715 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	119
Likely pathogenic	33
Uncertain significance	275
Likely benign	150
Benign	85

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1054038	NM_001174147.2(LMX1B):c.242T>G (p.Leu81Trp)	Pathogenic
1070212	NM_001174147.2(LMX1B):c.326+1G>C	Pathogenic
1070233	NM_001174147.2(LMX1B):c.750_751del (p.Glu250fs)	Pathogenic
1072036	NM_001174147.2(LMX1B):c.419G>T (p.Cys140Phe)	Pathogenic
1072237	NC_000009.11:g.(?129376729)(129377858_?)del	Pathogenic
1074743	NM_001174147.2(LMX1B):c.297del (p.Lys100fs)	Pathogenic
1076396	NM_001174147.2(LMX1B):c.332del (p.Phe111fs)	Pathogenic
1369797	NM_001174147.2(LMX1B):c.351_355dup (p.Met119fs)	Pathogenic
1392707	NM_001174147.2(LMX1B):c.289_291del (p.Arg97del)	Pathogenic
1407352	NM_001174147.2(LMX1B):c.285C>G (p.Tyr95Ter)	Pathogenic
1412425	NM_001174147.2(LMX1B):c.623del (p.Gly208fs)	Pathogenic
1417356	NM_001174147.2(LMX1B):c.748G>T (p.Glu250Ter)	Pathogenic
1418142	NM_001174147.2(LMX1B):c.844C>T (p.Gln282Ter)	Pathogenic
1438692	NM_001174147.2(LMX1B):c.409C>T (p.His137Tyr)	Pathogenic
1441083	NM_001174147.2(LMX1B):c.407_421del (p.Tyr136_Cys140del)	Pathogenic
1452247	NM_001174147.2(LMX1B):c.445C>T (p.Gln149Ter)	Pathogenic
1452363	NM_001174147.2(LMX1B):c.207dup (p.Arg70fs)	Pathogenic
1453005	NM_001174147.2(LMX1B):c.346_347insT (p.Ser116fs)	Pathogenic
1453257	NM_001174147.2(LMX1B):c.217del (p.Glu73fs)	Pathogenic
1453648	NM_001174147.2(LMX1B):c.739A>T (p.Lys247Ter)	Pathogenic
1455589	NM_001174147.2(LMX1B):c.398_399dup (p.Cys134fs)	Pathogenic
1457453	NM_001174147.2(LMX1B):c.178C>T (p.Gln60Ter)	Pathogenic
1457454	NM_001174147.2(LMX1B):c.208C>T (p.Arg70Ter)	Pathogenic
1457457	NM_001174147.2(LMX1B):c.484C>T (p.Gln162Ter)	Pathogenic
1457461	NM_001174147.2(LMX1B):c.819+2T>G	Pathogenic
1459041	NM_001174147.2(LMX1B):c.321C>G (p.Tyr107Ter)	Pathogenic
1459042	NM_001174147.2(LMX1B):c.327-2A>G	Pathogenic
1459796	NC_000009.11:g.(?129376729)(129458730_?)del	Pathogenic
1459797	NC_000009.11:g.(?129453095)(129458730_?)del	Pathogenic
1703546	GRCh37/hg19 9q33.3(chr9:129376720-129463802)	Pathogenic

SpliceAI

2253 predictions. Top by Δscore:

Variant	Effect	Δscore
9:126614587:GG:G	donor_gain	1.0000
9:126614588:GG:G	donor_gain	1.0000
9:126614589:G:GG	donor_gain	1.0000
9:126615570:G:GG	donor_gain	1.0000
9:126690828:A:AG	acceptor_gain	1.0000
9:126690832:GCAG:G	acceptor_loss	1.0000
9:126690834:A:AC	acceptor_loss	1.0000
9:126690834:A:AG	acceptor_gain	1.0000
9:126690834:AG:A	acceptor_gain	1.0000
9:126690835:G:GC	acceptor_gain	1.0000
9:126690835:GG:G	acceptor_gain	1.0000
9:126690835:GGC:G	acceptor_gain	1.0000
9:126690835:GGCT:G	acceptor_gain	1.0000
9:126690835:GGCTC:G	acceptor_gain	1.0000
9:126691039:GCTCC:G	donor_gain	1.0000
9:126691068:GGTG:G	donor_loss	1.0000
9:126691069:G:GA	donor_loss	1.0000
9:126691069:G:GG	donor_gain	1.0000
9:126691070:T:G	donor_loss	1.0000
9:126693139:CA:C	acceptor_loss	1.0000
9:126693140:A:AG	acceptor_gain	1.0000
9:126693140:AGT:A	acceptor_gain	1.0000
9:126693140:AGTGA:A	acceptor_loss	1.0000
9:126693141:G:GG	acceptor_gain	1.0000
9:126693141:GT:G	acceptor_gain	1.0000
9:126693141:GTG:G	acceptor_gain	1.0000
9:126693141:GTGAA:G	acceptor_gain	1.0000
9:126693320:AAAG:A	donor_loss	1.0000
9:126693323:GGTG:G	donor_loss	1.0000
9:126693324:G:C	donor_loss	1.0000

AlphaMissense

2660 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:126615409:T:A	C56S	1.000
9:126615409:T:C	C56R	1.000
9:126615410:G:A	C56Y	1.000
9:126615410:G:C	C56S	1.000
9:126615411:C:G	C56W	1.000
9:126615431:T:A	I63N	1.000
9:126615442:T:C	F67L	1.000
9:126615444:C:A	F67L	1.000
9:126615444:C:G	F67L	1.000
9:126615469:T:A	W76R	1.000
9:126615469:T:C	W76R	1.000
9:126615471:G:C	W76C	1.000
9:126615471:G:T	W76C	1.000
9:126615481:T:C	C80R	1.000
9:126615483:T:G	C80W	1.000
9:126615490:T:A	C83S	1.000
9:126615490:T:C	C83R	1.000
9:126615491:G:C	C83S	1.000
9:126615492:C:G	C83W	1.000
9:126615500:G:A	C86Y	1.000
9:126615512:T:A	L90H	1.000
9:126615526:T:G	Y95D	1.000
9:126615547:T:G	Y102D	1.000
9:126615550:T:C	C103R	1.000
9:126615551:G:A	C103Y	1.000
9:126615552:C:G	C103W	1.000
9:126615562:T:G	Y107D	1.000
9:126690840:T:C	F111L	1.000
9:126690842:C:A	F111L	1.000
9:126690842:C:G	F111L	1.000

dbSNP variants (sampled 300 via entrez): RS1000037378 (9:126626918 C>G,T), RS1000045670 (9:126665508 G>A,C), RS1000061474 (9:126619664 C>T), RS1000125143 (9:126686012 G>A), RS1000126776 (9:126614115 G>GCCA), RS1000144708 (9:126645759 C>T), RS1000231027 (9:126637646 G>A), RS1000248409 (9:126619099 G>A), RS1000273784 (9:126675134 A>G), RS1000276680 (9:126669208 C>T), RS1000334342 (9:126624595 G>C), RS1000337213 (9:126701035 G>A), RS1000369856 (9:126701233 C>T), RS1000395159 (9:126663402 C>A,T), RS1000407653 (9:126657308 G>A)

Disease associations

OMIM: gene MIM:602575 | disease phenotypes: MIM:161200, MIM:256020, MIM:603278, MIM:612164, MIM:203780

GenCC curated gene-disease

Disease	Classification	Inheritance
nail-patella syndrome	Definitive	Autosomal dominant
nail-patella-like renal disease	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
nail-patella syndrome	Definitive	AD

Mondo (10): nail-patella syndrome (MONDO:0008061), nail-patella-like renal disease (MONDO:0009724), kidney disorder (MONDO:0005240), neurodevelopmental disorder (MONDO:0700092), focal segmental glomerulosclerosis (MONDO:0100313), inherited focal segmental glomerulosclerosis (MONDO:0005363), nephrotic syndrome (MONDO:0005377), developmental and epileptic encephalopathy, 4 (MONDO:0012812), autosomal recessive Alport syndrome (MONDO:0008762), minimal change disease (MONDO:0006835)

Orphanet (7): Nail-patella-like renal disease (Orphanet:2613), Nail-patella syndrome (Orphanet:2614), Early infantile developmental and epileptic encephalopathy (Orphanet:1934), Dravet syndrome (Orphanet:33069), STXBP1-related encephalopathy (Orphanet:599373), Alport syndrome (Orphanet:63), Autosomal recessive Alport syndrome (Orphanet:88919)

HPO phenotypes

155 total (30 of 155 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000046	Small scrotum
HP:0000054	Micropenis
HP:0000077	Abnormality of the kidney
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000099	Glomerulonephritis
HP:0000100	Nephrotic syndrome
HP:0000123	Nephritis
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000204	Cleft upper lip
HP:0000233	Thin vermilion border
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000293	Full cheeks
HP:0000311	Round face
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000407	Sensorineural hearing impairment
HP:0000414	Bulbous nose
HP:0000421	Epistaxis
HP:0000445	Wide nose
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000478	Abnormality of the eye

GWAS associations

49 associations (top):

Study	Trait	p-value
GCST000830_23	Body mass index	1.000000e-07
GCST002367_15	Social communication problems	3.000000e-06
GCST002783_398	Body mass index	2.000000e-10
GCST002783_524	Body mass index	2.000000e-08
GCST002783_584	Body mass index	2.000000e-08
GCST003177_25	Childhood body mass index	9.000000e-09
GCST003476_10	Eyebrow thickness	3.000000e-06
GCST003784_12	Multiple system atrophy	5.000000e-06
GCST003989_1	Chin dimples	1.000000e-08
GCST003996_41	Monobrow	1.000000e-15
GCST004904_83	Body mass index	3.000000e-08
GCST004988_638	Breast cancer	9.000000e-09
GCST005406_1	Open-angle glaucoma and optic cup area	5.000000e-08
GCST005407_3	Glaucoma (primary open-angle)	9.000000e-07
GCST005580_140	Intraocular pressure	7.000000e-32
GCST005580_142	Intraocular pressure	7.000000e-31
GCST005982_4	Calcium levels	1.000000e-09
GCST006065_26	Glaucoma (primary open-angle)	1.000000e-17
GCST006394_25	Intraocular pressure	5.000000e-27
GCST006394_82	Intraocular pressure	2.000000e-15
GCST006394_83	Intraocular pressure	1.000000e-31
GCST006395_17	Glaucoma	3.000000e-17
GCST006395_35	Glaucoma	6.000000e-17
GCST006395_37	Glaucoma	4.000000e-14
GCST006412_108	Intraocular pressure	1.000000e-31
GCST006412_30	Intraocular pressure	4.000000e-19
GCST006802_10	Body mass index	9.000000e-06
GCST006926_3	Osteoarthritis (hip)	8.000000e-12
GCST006979_552	Heel bone mineral density	4.000000e-13
GCST007673_4	3-month functional outcome in ischaemic stroke (modified Rankin score)	5.000000e-06

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0005427	social communication impairment
EFO:0007906	synophrys measurement
EFO:0004695	intraocular pressure measurement
EFO:0004838	calcium measurement
EFO:0009270	heel bone mineral density
EFO:0009603	stroke outcome severity measurement
EFO:0009944	Antiglaucoma preparations and miotics use measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0011014	health-related quality of life measurement
EFO:0004458	C-reactive protein measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
D009261	Nail-Patella Syndrome	C05.550.629; C16.131.077.606; C16.320.600; C17.800.529.400
D009402	Nephrosis, Lipoid	C12.050.351.968.419.630.477; C12.200.777.419.630.477; C12.950.419.630.477
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643
D065886	Neurodevelopmental Disorders	F03.625
C567404	Epileptic Encephalopathy, Early Infantile, 4 (supp.)
C537228	Salcedo syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	2
bisphenol A	affects methylation	1
ethyl-p-hydroxybenzoate	increases expression	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	affects methylation	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
abrine	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Calcitriol	increases expression	1
Carmustine	decreases expression	1
Lead	affects expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Methapyrilene	affects methylation	1
Morphine	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Aflatoxin M1	decreases expression	1
Cadmium Chloride	increases expression	1
Particulate Matter	increases expression, increases abundance	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A3Y6	SEES3-1V human LMX1B, clone1	Embryonic stem cell	Male
CVCL_A3Y7	SEES3-1V human LMX1B, clone2	Embryonic stem cell	Male
CVCL_A3Y8	SEES3-1V human LMX1B, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00067990	PHASE4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	PHASE4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	PHASE4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	PHASE4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	PHASE4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	PHASE4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	PHASE4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	PHASE4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	PHASE4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	PHASE4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	PHASE4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	PHASE4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	PHASE4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	PHASE4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	PHASE4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
NCT01101698	PHASE4	UNKNOWN	Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
NCT01150201	PHASE4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01155141	PHASE4	COMPLETED	Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
NCT01228279	PHASE4	COMPLETED	Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
NCT01334333	PHASE4	COMPLETED	Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients
NCT01437943	PHASE4	TERMINATED	Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients
NCT01545479	PHASE4	COMPLETED	Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition
NCT01614431	PHASE4	COMPLETED	N Acetyl Cysteine for Cystinosis Patients
NCT01631149	PHASE4	COMPLETED	Effect of Deep BLock on Intraoperative Surgical Conditions
NCT01722513	PHASE4	UNKNOWN	Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy
NCT01985360	PHASE4	COMPLETED	ISCHEMIA-Chronic Kidney Disease Trial
NCT02311010	PHASE4	UNKNOWN	Practical Use of Advagraf de Novo After Kidney Transplantation According to Recipient Genetic Polymorphism
NCT02413073	PHASE4	COMPLETED	Whole Body Vibration in Kidney Disease
NCT02444013	PHASE4	UNKNOWN	Folic Acid for Prevention of Contrast Induced Nephropathy
NCT02663713	PHASE4	COMPLETED	A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor to Clopidogrel in Patients With Prior Myocardial Infarction
NCT02707809	PHASE4	COMPLETED	Effects of Dexmedetomidine on Microcirculation of Kidney Transplant Recipient
NCT02761577	PHASE4	COMPLETED	A Prospective Study on Incidence and Prevention of Contrast-induced Nephropathy in Croatia
NCT03029351	PHASE4	TERMINATED	GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes