LMO4

Summary

LMO4 (LIM domain only 4, HGNC:6644) is a protein-coding gene on chromosome 1p22.3, encoding LIM domain transcription factor LMO4 (P61968). Transcription cofactor.

This gene encodes a cysteine-rich protein that contains two LIM domains but lacks a DNA-binding homeodomain. The encoded protein may play a role as a transcriptional regulator or as an oncogene.

Source: NCBI Gene 8543 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 26 total — 1 likely-pathogenic
• MANE Select transcript: NM_006769

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6644
Approved symbol	LMO4
Name	LIM domain only 4
Location	1p22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000143013
Ensembl biotype	protein_coding
OMIM	603129
Entrez	8543

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000370542, ENST00000370544, ENST00000489303, ENST00000495705, ENST00000887812, ENST00000887813, ENST00000887814, ENST00000887815, ENST00000887816, ENST00000887817, ENST00000930941, ENST00000964013

RefSeq mRNA: 2 — MANE Select: NM_006769 NM_001369491, NM_006769

CCDS: CCDS713

Canonical transcript exons

ENST00000370544 — 5 exons

Exon	Start	End
ENSE00001067166	87328880	87329244
ENSE00001452984	87344788	87348923
ENSE00003458515	87332013	87332251
ENSE00003568548	87339536	87339632
ENSE00003603484	87340047	87340202

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 98.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 94.7379 / max 2985.5518, expressed in 1819 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3902	55.3980	1812
3898	23.2524	1769
3908	6.2233	1248
3899	4.6312	1462
3904	1.5600	832
3897	0.8432	371
3905	0.7836	423
201570	0.6147	304
3903	0.5160	269
3907	0.4132	160

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsolateral prefrontal cortex	UBERON:0009834	98.72	gold quality
prefrontal cortex	UBERON:0000451	98.61	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.61	gold quality
superior frontal gyrus	UBERON:0002661	98.45	gold quality
frontal cortex	UBERON:0001870	98.41	gold quality
parietal lobe	UBERON:0001872	98.40	gold quality
postcentral gyrus	UBERON:0002581	98.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.28	gold quality
neocortex	UBERON:0001950	98.20	gold quality
frontal pole	UBERON:0002795	98.11	gold quality
cingulate cortex	UBERON:0003027	98.09	gold quality
right frontal lobe	UBERON:0002810	98.05	gold quality
anterior cingulate cortex	UBERON:0009835	98.05	gold quality
cerebral cortex	UBERON:0000956	97.99	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.69	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.49	gold quality
orbitofrontal cortex	UBERON:0004167	97.30	gold quality
telencephalon	UBERON:0001893	97.16	gold quality
Ammon’s horn	UBERON:0001954	97.16	gold quality
entorhinal cortex	UBERON:0002728	97.15	gold quality
pylorus	UBERON:0001166	97.07	gold quality
temporal lobe	UBERON:0001871	96.84	gold quality
CA1 field of hippocampus	UBERON:0003881	96.77	gold quality
cortical plate	UBERON:0005343	96.73	gold quality
amygdala	UBERON:0001876	96.70	gold quality
body of stomach	UBERON:0001161	96.68	gold quality
occipital lobe	UBERON:0002021	96.60	gold quality
stromal cell of endometrium	CL:0002255	96.43	gold quality
nasal cavity mucosa	UBERON:0001826	96.43	gold quality
fundus of stomach	UBERON:0001160	96.40	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	1969.04
E-MTAB-9067	yes	954.67
E-HCAD-56	yes	752.93
E-HCAD-6	yes	660.54
E-MTAB-8495	yes	482.99
E-HCAD-35	yes	42.07
E-GEOD-134144	yes	31.18
E-HCAD-5	yes	17.38
E-CURD-112	yes	16.69
E-CURD-122	yes	9.99
E-HCAD-10	yes	9.95
E-MTAB-9801	yes	9.81
E-GEOD-130148	yes	7.66
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
BMP7	Activation
BRCA1	Repression
DLG4	Repression
ESR1	Unknown
MTA1	Unknown

Upstream regulators (CollecTRI, top): ESR1, GATA3, MTA1, NHLH1, PAX3, SP1, TP53

miRNA regulators (miRDB)

205 targeting LMO4, 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-4795-3P	100.00	74.62	4024
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-126-5P	100.00	72.71	3180
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6744-5P	99.93	66.82	748

Literature-anchored findings (GeneRIF, showing 30)

• These findings reveal a novel complex between BRCA1, LMO4, and CtIP and indicate a role for LMO4 as a repressor of BRCA1 activity in breast tissue. (PMID:11751867)
• 1H, 15N and 13C assignments of FLIN4, an intramolecular LMO4:ldb1 complex (PMID:12153047)
• Lmo4 RNA overexpression interferes with neuritic outgrowth,anti-sense Lmo4 RNA expression favors neuritogenesis in SH-SY5Y cells. Changes in Lmo4 RNA expression levels might alter the rate of neuritic outgrowth in the developing and adult nervous system. (PMID:12877980)
• LMO4 interaction modulates the interleukin-6 receptor subunit glycoprotein 130 complex and its signaling (PMID:15677447)
• LMO4 is consistently more highly expressed in the embryonic right perisylvian cerebral cortex than in the left (PMID:15894532)
• LMO4 in breast epithelium contributes directly to breast neoplasia by altering the rate of cellular proliferation and promoting cell invasion. (PMID:15897450)
• Artificial intramolecular cyclic protein complex between two interacting proteins: the largely unstable LIM-only protein 4 (LMO4) and an unstructured domain of LIM domain binding protein 1 (ldb1). (PMID:17001033)
• In this study, patients whose tumours exhibited high LMO4 expression had a significant survival advantage following operative resection (PMID:18231110)
• LMO4 protects neurons from ischemic brain injury, in part through its requirement as an essential cofactor of PPAR gamma (PMID:19020036)
• Results suggested that LMO4 is overexpressed at late stages in carcinogenesis of pancreatic cancer. (PMID:19099607)
• Lmo4 expression coincides with the timing of the development of the somatosensory barrel field. (PMID:19111533)
• LMO4 is a novel cell cycle regulator with a key role in mediating ErbB2-induced proliferation, a hallmark of ErbB2-positive disease. (PMID:19648968)
• data indicate that LMO4 has similar cellular effects in normal mammary epithelial cells and breast cancer cells, and also provide direct evidence for the idea that normal development and carcinogenesis share conserved molecular mechanisms (PMID:20526802)
• LMO4 is over-expressed in highly invasive rhabdomyosarcoma, alveolar cells (PMID:21271214)
• LMO4 expression in squamous cell carcinoma of the anterior tongue (PMID:21362019)
• LMO4 is a direct target of p53 and inhibits p53-mediated proliferative inhibition of breast cancer cells through interacting p53 (PMID:22906635)
• oncoprotein HBXIP is able to activate the transcriptional coregulatory protein LMO4 through transcription factor Sp1 in promotion of proliferation of breast cancer cells. (PMID:23291272)
• Data suggest that overexpression of LMO4 may disrupt some of the normal tumour suppressor activities of CtIP, thereby contributing to breast cancer progression. (PMID:23353824)
• Low LMO4 mRNA levels were associated with response to erlotinib in non-small-cell lung cancer. (PMID:23407556)
• the association of high levels of LMO4 with aggressive neuroblastomas is dependent on LMO4 regulation of cadherin expression and hence, tumor invasiveness (PMID:23407937)
• Existence of a region in the lateral portion of the mammalian cochlea that is competent to make an organ of Corti is demonstrated in the absence of LMO4 function. (PMID:25057208)
• Clim2, in a complex with LMO4, supports mammary stem cells by directly targeting the Fgfr2 promoter in basal cells to increase its expression (PMID:25079073)
• LMO4 appears to form a hub in protein-protein interaction networks, linking numerous pathways within cells. (PMID:25310299)
• Lmo4 participates in the regulation of lung epithelial cell proliferation but is not essential for tumor progression. (PMID:26048572)
• LMO4 appears to mediate IL-23-related responses in psoriatic keratinocytes and is a potential therapeutic target in psoriasis. (PMID:29258893)
• Long noncoding RNA SNHG1 promotes breast cancer progression by regulation of LMO4. (PMID:32323846)
• Research and Clinical Significance of the Differentially Expressed Genes TP63 and LMO4 in Human Immunodeficiency Virus-Related Penile Squamous Cell Carcinoma. (PMID:33906487)
• MicroRNA-139-5p Alleviates High Glucose-Triggered Human Retinal Pigment Epithelial Cell Injury by Targeting LIM-Only Factor 4. (PMID:34725544)
• CircLDLR Promotes Papillary Thyroid Carcinoma Tumorigenicity by Regulating miR-637/LMO4 Axis. (PMID:34925640)
• IL-6 Up-Regulates Expression of LIM-Domain Only Protein 4 in Psoriatic Keratinocytes through Activation of the MEK/ERK/NF-kappaB Pathway. (PMID:38320628)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lmo4b	ENSDARG00000054749
mus_musculus	Lmo4	ENSMUSG00000028266
rattus_norvegicus	Lmo4	ENSRNOG00000009205

Paralogs (20): FHL1 (ENSG00000022267), LMO3 (ENSG00000048540), LHX5 (ENSG00000089116), ZFHX4 (ENSG00000091656), LHX2 (ENSG00000106689), LHX6 (ENSG00000106852), LHX3 (ENSG00000107187), LHX4 (ENSG00000121454), LMO2 (ENSG00000135363), ZFHX2 (ENSG00000136367), LMX1B (ENSG00000136944), ZFHX3 (ENSG00000140836), LHX9 (ENSG00000143355), CRIP3 (ENSG00000146215), LHX8 (ENSG00000162624), LMX1A (ENSG00000162761), LMO1 (ENSG00000166407), CRIP2 (ENSG00000182809), CRIP1 (ENSG00000213145), LHX1 (ENSG00000273706)

Protein

Protein identifiers

LIM domain transcription factor LMO4 — P61968 (reviewed: P61968)

Alternative names: Breast tumor autoantigen, LIM domain only protein 4

All UniProt accessions (1): P61968

UniProt curated annotations — full annotation on UniProt →

Function. Transcription cofactor. Plays a role in establishing motor neuron identity, in concert with MNX1, acting, at least in part, to disrupt LDB1-LHX3 complexes thereby negatively modulating interneuron genes in motor neurons.

Subunit / interactions. Interacts strongly with LDBS. Interacts with LDB2 and LDB1. Interaction with complexes consisting of at least LDB1 and LHX3, acts to disassemble the complex; may preferentially disassemble LDB1-LHX3 complexes rather than complexes consisting of LDB1, LHX3 and ISL1. Interacts (via the LIM zinc-binding domain 1) with RBBP8. Interacts with both RPPB8 and LDB1 through the same face and cannot bind to both proteins simultaneously. Interacts with BRCA1 (via the BRCT domains); the interaction represses BRCA1 transcriptional activity. Interacts with DEAF1; LMO4 blocks export from nucleus.

RefSeq proteins (2): NP_001356420, NP_006760* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain
IPR050945	LMO_RBTN_TF	Family

Pfam: PF00412

UniProt features (21 total): strand 8, helix 6, turn 4, domain 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9F5B	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61968-F1	86.01	0.74

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 502 (showing top): PID_SHP2_PATHWAY, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, FREAC2_01, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_REGULATION_OF_PHOSPHORYLATION, NKX25_02, GCANCTGNY_MYOD_Q6

GO Biological Process (18): negative regulation of transcription by RNA polymerase II (GO:0000122), neural tube closure (GO:0001843), ventricular septum development (GO:0003281), motor neuron axon guidance (GO:0008045), ventral spinal cord interneuron differentiation (GO:0021514), spinal cord motor neuron cell fate specification (GO:0021520), spinal cord association neuron differentiation (GO:0021527), regulation of cell migration (GO:0030334), negative regulation of protein-containing complex assembly (GO:0031333), positive regulation of kinase activity (GO:0033674), regulation of cell fate specification (GO:0042659), positive regulation of transcription by RNA polymerase II (GO:0045944), thymus development (GO:0048538), regulation of cell activation (GO:0050865), regulation of transcription by RNA polymerase II (GO:0006357), tissue development (GO:0009888), spinal cord motor neuron differentiation (GO:0021522), regulation of developmental process (GO:0050793)

GO Molecular Function (5): transcription corepressor activity (GO:0003714), metal ion binding (GO:0046872), DNA-binding transcription factor binding (GO:0140297), transcription coregulator activity (GO:0003712), protein binding (GO:0005515)

GO Cellular Component (4): transcription regulator complex (GO:0005667), cell leading edge (GO:0031252), RNA polymerase II transcription regulator complex (GO:0090575), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
cell differentiation in spinal cord	3
central nervous system neuron differentiation	3
regulation of transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
ventral spinal cord development	2
primary neural tube formation	1
tube closure	1
cardiac ventricle development	1
cardiac septum development	1
axon guidance	1
spinal cord motor neuron differentiation	1
neuron fate specification	1
dorsal spinal cord development	1
cell migration	1
regulation of cell motility	1
regulation of protein-containing complex assembly	1
negative regulation of cellular component organization	1
protein-containing complex assembly	1
kinase activity	1
positive regulation of phosphorylation	1
positive regulation of catalytic activity	1
regulation of kinase activity	1
cell fate specification	1
regulation of cell fate commitment	1
positive regulation of DNA-templated transcription	1
hematopoietic or lymphoid organ development	1
gland development	1
cell activation	1
regulation of cellular process	1
regulation of multicellular organismal process	1
regulation of DNA-templated transcription	1
anatomical structure development	1
developmental process	1
regulation of biological process	1
transcription coregulator activity	1
cation binding	1
transcription factor binding	1
transcription regulator activity	1
binding	1

Protein interactions and networks

STRING

424 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LMO4	LDB1	Q86U70	905
LMO4	KLF1	Q13351	637
LMO4	RBBP8	Q99708	583
LMO4	GATA6	P78327	472
LMO4	BRCA1	P38398	433
LMO4	NSMF	Q6X4W1	366
LMO4	INA	Q16352	342
LMO4	DEPDC1	Q5TB30	322
LMO4	SH2D4B	Q5SQS7	319
LMO4	EFNB2	P52799	312
LMO4	PIGT	Q969N2	302
LMO4	LRRTM1	Q86UE6	297
LMO4	EFCC1	Q9HA90	290
LMO4	PCSK6	P29122	289
LMO4	TMEM167A	Q8TBQ9	272

IntAct

430 interactions, top by confidence:

A	B	Type	Score
LMO4	SMAD4	psi-mi:“MI:0915”(physical association)	0.830
SMAD4	LMO4	psi-mi:“MI:0915”(physical association)	0.830
LDB2	LMO4	psi-mi:“MI:0915”(physical association)	0.800
GRHL2	LMO4	psi-mi:“MI:0915”(physical association)	0.780
LMO4	GRHL2	psi-mi:“MI:0915”(physical association)	0.780
CCDC102B	LMO4	psi-mi:“MI:0915”(physical association)	0.720
LMO4	KRT15	psi-mi:“MI:0915”(physical association)	0.720
LMO4	GABPB1	psi-mi:“MI:0915”(physical association)	0.720
GOLGA2	LMO4	psi-mi:“MI:0915”(physical association)	0.720
LMO4	KRT31	psi-mi:“MI:0915”(physical association)	0.720
KANK2	LMO4	psi-mi:“MI:0915”(physical association)	0.720
KIAA1958	LMO4	psi-mi:“MI:0915”(physical association)	0.720
TFIP11	LMO4	psi-mi:“MI:0915”(physical association)	0.720
LMO4	CCDC102B	psi-mi:“MI:0915”(physical association)	0.720
KRT15	LMO4	psi-mi:“MI:0915”(physical association)	0.720
GABPB1	LMO4	psi-mi:“MI:0915”(physical association)	0.720
KRT31	LMO4	psi-mi:“MI:0915”(physical association)	0.720
LMO4	KANK2	psi-mi:“MI:0915”(physical association)	0.720
LMO4	KIAA1958	psi-mi:“MI:0915”(physical association)	0.720
LMO4	GOLGA2	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (210): LMO4 (Two-hybrid), LMO4 (Two-hybrid), LMO4 (Two-hybrid), LMO4 (Two-hybrid), LMO4 (Two-hybrid), LMO4 (Two-hybrid), LMO4 (Two-hybrid), LMO4 (Two-hybrid), LMO4 (Two-hybrid), LMO4 (Two-hybrid), LMO4 (Two-hybrid), LMO4 (Two-hybrid), LDB1 (Two-hybrid), PDE4DIP (Two-hybrid), CALCOCO2 (Two-hybrid)

ESM2 similar proteins: A0A2R8RWN9, A5PKA5, O15294, O89050, P25791, P25801, P48059, P49136, P49139, P49336, P56558, P61201, P61202, P61203, P61968, P61969, P79101, P81436, Q08211, Q1LZ94, Q27HV0, Q28141, Q2KJ33, Q3SWZ8, Q3UHD6, Q5FVB2, Q5M8V8, Q5R874, Q5RB35, Q5SRY7, Q5ZIH0, Q6DJ06, Q7Z4I7, Q801P0, Q8AW92, Q8CGY8, Q8K4V4, Q8R3L8, Q90XH3, Q91854

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of the cornified envelope	8	13.8×	2e-05
Keratinization	8	8.7×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	9	25.8×	4e-08
morphogenesis of an epithelium	6	24.6×	3e-05
epithelial cell differentiation	8	16.7×	7e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	13
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
979897	GRCh37/hg19 1p31.1-22.2(chr1:80804502-89490384)x3	Likely pathogenic

SpliceAI

711 predictions. Top by Δscore:

Variant	Effect	Δscore
1:87332001:C:A	acceptor_gain	1.0000
1:87332010:CA:C	acceptor_loss	1.0000
1:87332011:A:AC	acceptor_loss	1.0000
1:87332012:G:GT	acceptor_loss	1.0000
1:87332012:GACC:G	acceptor_gain	1.0000
1:87332248:TTAGG:T	donor_loss	1.0000
1:87332249:TAGGT:T	donor_loss	1.0000
1:87332250:AGGTA:A	donor_loss	1.0000
1:87332251:GGTA:G	donor_loss	1.0000
1:87332252:G:GG	donor_gain	1.0000
1:87332252:GTAAG:G	donor_loss	1.0000
1:87332253:T:G	donor_loss	1.0000
1:87339531:TTCA:T	acceptor_loss	1.0000
1:87339532:TCAG:T	acceptor_loss	1.0000
1:87339533:CAGG:C	acceptor_loss	1.0000
1:87339534:A:AG	acceptor_gain	1.0000
1:87339534:A:G	acceptor_loss	1.0000
1:87339535:G:GG	acceptor_gain	1.0000
1:87339535:GGTT:G	acceptor_gain	1.0000
1:87339613:GCAA:G	donor_gain	1.0000
1:87339614:C:T	donor_gain	1.0000
1:87339630:AAG:A	donor_loss	1.0000
1:87339631:AGGTA:A	donor_loss	1.0000
1:87339632:GG:G	donor_loss	1.0000
1:87339633:GT:G	donor_loss	1.0000
1:87340042:TTCAG:T	acceptor_loss	1.0000
1:87340044:CA:C	acceptor_loss	1.0000
1:87340045:A:AC	acceptor_loss	1.0000
1:87340045:A:AG	acceptor_gain	1.0000
1:87340045:AGT:A	acceptor_gain	1.0000

AlphaMissense

1088 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:87332082:T:A	C23S	1.000
1:87332082:T:C	C23R	1.000
1:87332083:G:C	C23S	1.000
1:87332144:G:C	W43C	1.000
1:87332144:G:T	W43C	1.000
1:87332154:T:C	C47R	1.000
1:87332158:T:A	L48H	1.000
1:87332158:T:C	L48P	1.000
1:87332163:T:A	C50S	1.000
1:87332163:T:C	C50R	1.000
1:87332164:G:C	C50S	1.000
1:87332165:C:G	C50W	1.000
1:87332173:G:A	C53Y	1.000
1:87332174:C:G	C53W	1.000
1:87332230:T:C	L72P	1.000
1:87332232:T:A	C73S	1.000
1:87332232:T:C	C73R	1.000
1:87332233:G:A	C73Y	1.000
1:87332233:G:C	C73S	1.000
1:87332234:C:G	C73W	1.000
1:87332242:A:T	D76V	1.000
1:87339540:T:C	F81L	1.000
1:87339542:T:A	F81L	1.000
1:87339542:T:G	F81L	1.000
1:87339558:T:A	C87S	1.000
1:87339558:T:C	C87R	1.000
1:87339559:G:A	C87Y	1.000
1:87339559:G:C	C87S	1.000
1:87339560:C:G	C87W	1.000
1:87339567:T:C	C90R	1.000

dbSNP variants (sampled 300 via entrez): RS1000054907 (1:87342939 C>G), RS1000138138 (1:87348583 G>A), RS1000525030 (1:87337076 C>A,G,T), RS1000631252 (1:87328354 C>T), RS1000694514 (1:87333818 C>T), RS1000882420 (1:87348936 T>C), RS1000917641 (1:87348045 C>A,T), RS1000931222 (1:87343037 T>A,C), RS1000957592 (1:87336620 G>A), RS1000961435 (1:87331030 G>C), RS1001073660 (1:87336895 C>T), RS1001152463 (1:87342442 C>T), RS1001153997 (1:87334006 A>ATGGGTCCGCTTGTATTCC), RS1001168409 (1:87328933 C>G,T), RS1001391304 (1:87342767 C>T)

Disease associations

OMIM: gene MIM:603129 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST000211_4	Response to TNF antagonist treatment	5.000000e-06
GCST001134_12	White blood cell types	6.000000e-06
GCST003054_1	Gait rhythm	2.000000e-07
GCST003054_4	Gait rhythm	2.000000e-08
GCST003520_7	Breast cancer	4.000000e-08
GCST003818_41	Resting heart rate	7.000000e-18
GCST003992_3	Photic sneeze reflex	1.000000e-10
GCST004029_3	Angiotensin-converting enzyme inhibitor intolerance	9.000000e-07
GCST004093_11	Prostate-specific antigen levels	7.000000e-20
GCST005975_6	Eosinophil count	7.000000e-10
GCST005976_11	White blood cell count (basophil)	1.000000e-24
GCST006065_9	Glaucoma (primary open-angle)	4.000000e-09
GCST011358_13	Academic attainment (English)	4.000000e-06
GCST90000047_9	Age at first sexual intercourse	3.000000e-08
GCST90011898_69	Alanine aminotransferase levels	6.000000e-11
GCST90011899_34	Aspartate aminotransferase levels	1.000000e-20

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004653	response to TNF antagonist
EFO:0004842	eosinophil count
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0005090	basophil count
EFO:0011015	educational attainment
EFO:0009749	age at first sexual intercourse measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

58 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation, affects cotreatment, increases expression	5
trichostatin A	affects cotreatment, increases expression, decreases expression	3
Acetaminophen	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression, affects cotreatment	2
entinostat	affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	increases expression	2
Particulate Matter	increases abundance, increases expression, affects cotreatment	2
methylmercuric chloride	increases expression, decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
lead acetate	increases expression	1
arsenite	increases methylation	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
zinc chromate	increases abundance, decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
triadimefon	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	affects expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
ICG 001	increases expression	1
dorsomorphin	decreases expression, increases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SV70	HAP1 LMO4 (-) 1	Cancer cell line	Male
CVCL_SV71	HAP1 LMO4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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