LRIG2

Summary

LRIG2 (leucine rich repeats and immunoglobulin like domains 2, HGNC:20889) is a protein-coding gene on chromosome 1p13.2, encoding Leucine-rich repeats and immunoglobulin-like domains protein 2 (O94898).

This gene encodes a transmembrane protein containing leucine-rich repeats and immunoglobulin-like domains. The encoded protein promotes epidermal growth factor signalling, resulting in increased proliferation. Its expression in the cytoplasm of glioma cells is correlated with poor survival. Mutations in this gene can cause urofacial syndrome. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 9860 — RefSeq curated summary.

At a glance

• Gene–disease (curated): urofacial syndrome 2 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 232 total — 8 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 21
• MANE Select transcript: NM_014813

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20889
Approved symbol	LRIG2
Name	leucine rich repeats and immunoglobulin like domains 2
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0806
Ensembl gene	ENSG00000198799
Ensembl biotype	protein_coding
OMIM	608869
Entrez	9860

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000361127, ENST00000466069, ENST00000466161, ENST00000470000, ENST00000492207, ENST00000890455, ENST00000890456, ENST00000922864, ENST00000922865, ENST00000969894, ENST00000969895

RefSeq mRNA: 2 — MANE Select: NM_014813 NM_001312686, NM_014813

CCDS: CCDS30808

Canonical transcript exons

ENST00000361127 — 18 exons

Exon	Start	End
ENSE00000958001	113073198	113073645
ENSE00000958002	113091318	113091383
ENSE00000958003	113093206	113093280
ENSE00000958004	113093430	113093564
ENSE00000958005	113094339	113094482
ENSE00000958006	113094612	113094755
ENSE00000958007	113095874	113096017
ENSE00000958008	113096222	113096365
ENSE00000958009	113098705	113098785
ENSE00001906083	113123875	113132260
ENSE00003472895	113114427	113114876
ENSE00003488881	113100211	113100282
ENSE00003491361	113110242	113110562
ENSE00003507971	113112479	113112760
ENSE00003572183	113119233	113119523
ENSE00003596102	113107594	113107757
ENSE00003640021	113100420	113100488
ENSE00003642937	113116287	113116436

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 93.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.4324 / max 83.8690, expressed in 1787 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4716	13.4324	1787

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	93.30	gold quality
endothelial cell	CL:0000115	93.01	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.79	gold quality
tibia	UBERON:0000979	92.16	gold quality
germinal epithelium of ovary	UBERON:0001304	91.69	gold quality
medial globus pallidus	UBERON:0002477	91.31	gold quality
parietal pleura	UBERON:0002400	90.54	gold quality
pleura	UBERON:0000977	89.72	gold quality
visceral pleura	UBERON:0002401	89.28	gold quality
globus pallidus	UBERON:0001875	89.21	gold quality
tendon	UBERON:0000043	88.65	gold quality
middle temporal gyrus	UBERON:0002771	88.44	gold quality
jejunal mucosa	UBERON:0000399	87.98	gold quality
seminal vesicle	UBERON:0000998	87.48	gold quality
calcaneal tendon	UBERON:0003701	87.11	gold quality
corpus epididymis	UBERON:0004359	86.98	gold quality
corpus callosum	UBERON:0002336	86.81	gold quality
gingival epithelium	UBERON:0001949	86.55	gold quality
epithelium of nasopharynx	UBERON:0001951	86.32	gold quality
adrenal tissue	UBERON:0018303	86.27	gold quality
caput epididymis	UBERON:0004358	86.14	gold quality
upper leg skin	UBERON:0004262	84.51	gold quality
pigmented layer of retina	UBERON:0001782	84.27	gold quality
entorhinal cortex	UBERON:0002728	84.14	gold quality
gingiva	UBERON:0001828	83.55	gold quality
skin of hip	UBERON:0001554	83.49	gold quality
cauda epididymis	UBERON:0004360	83.43	gold quality
subthalamic nucleus	UBERON:0001906	83.21	gold quality
endometrium	UBERON:0001295	82.90	gold quality
postcentral gyrus	UBERON:0002581	82.90	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.51

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOS, TAF1, YY1

miRNA regulators (miRDB)

72 targeting LRIG2, 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-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548AW	99.99	72.57	3559
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-1229-3P	99.97	66.49	906
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-4731-5P	99.89	67.23	2537

Literature-anchored findings (GeneRIF, showing 18)

• LRIG2 was found to be a glycoprotein with an molecular weight of 132 kDa, which was encoded by a gene on human chromosome 1p13 and its mRNA was present in all tissues analyzed. (PMID:15145052)
• LRIG proteins may have a role in epidermal homeostasis and psoriasis (PMID:18037903)
• This is the first report of an LRIG protein showing a negative effect on survival, suggesting that LRIG2 might have a function different from that of LRIG1, and possibly contributing to the etiology of oligodendroglioma. (PMID:18992012)
• LRIG1 and LRIG2 expressions were seen in precancerous cervical epithelium and found to increase with increasing grade. (PMID:21632100)
• LRIG2 gene is overexpressed in invasive pituitary adenoma. (PMID:21823015)
• Cytoplasmic expression of LRIG2 is associated with meningiomas. (PMID:22484910)
• A subset of urofacial syndrome-affected individuals have biallelic mutations in LRIG2 (PMID:23313374)
• Role of LRIG2 in cancer [review] (PMID:27628597)
• Study demonstrated that LRIG2 promoted the PDGFRBinduced proliferation of glioblastoma multiforme cells in vitro and in vivo through regulating the PDGFRB signalingmediated cell cycle progression. (PMID:30015847)
• LRIG2 was identified as the downstream target of miR-149-5p and its expression was regulated by LINC00461/miR-149-5p axis. (PMID:30879766)
• Study discovered novel homozygous missense LRIG2 variants that were predicted to be pathogenic in 2 individuals with non-syndromic bladder outlet obstruction. These observations provide evidence that a peripheral neuropathy is central to the pathobiology of functional bladder outlet obstruction in urofacial syndrome and emphasize the importance of LRIG2 and heparanase 2 for nerve patterning in the urinary tract. (PMID:30885509)
• epidermal LRIG2 excess is associated with activated EGFR/ERBB4-MAPK signaling and accelerated tumor progression. (PMID:31580518)
• Targeting LRIG2 overcomes resistance to EGFR inhibitor in glioblastoma by modulating GAS6/AXL/SRC signaling. (PMID:31988476)
• A SINE-VNTR-Alu in the LRIG2 Promoter Is Associated with Gene Expression at the Locus. (PMID:33187279)
• LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes. (PMID:33469151)
• Prognostic significance of LRIG2 and LRIG3 proteins in urothelial bladder carcinoma. (PMID:34839782)
• LRIG2 regulates cell proliferation, migration and apoptosis of osteosarcoma. (PMID:36183058)
• A SINE-VNTR-Alu at the LRIG2 locus is associated with proximal and distal gene expression in CRISPR and population models. (PMID:38191889)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrig2	ENSDARG00000078561
mus_musculus	Lrig2	ENSMUSG00000032913
rattus_norvegicus	Lrig2	ENSRNOG00000019957
drosophila_melanogaster	Con	FBGN0005775
drosophila_melanogaster	kek3	FBGN0028370
caenorhabditis_elegans	lron-9	WBGENE00011971
caenorhabditis_elegans		WBGENE00020649

Paralogs (22): CHADL (ENSG00000100399), LGI1 (ENSG00000108231), LGR6 (ENSG00000133067), CHAD (ENSG00000136457), LRIG3 (ENSG00000139263), LGR5 (ENSG00000139292), LRIG1 (ENSG00000144749), LRRTM2 (ENSG00000146006), LRIT1 (ENSG00000148602), LGI2 (ENSG00000153012), LGI4 (ENSG00000153902), LRRC52 (ENSG00000162763), ELFN2 (ENSG00000166897), LGI3 (ENSG00000168481), LRG1 (ENSG00000171236), CPN2 (ENSG00000178772), LRIT3 (ENSG00000183423), LRRC26 (ENSG00000184709), LGR4 (ENSG00000205213), ELFN1 (ENSG00000225968), LRRC24 (ENSG00000254402), TRIL (ENSG00000255690)

Protein

Protein identifiers

Leucine-rich repeats and immunoglobulin-like domains protein 2 — O94898 (reviewed: O94898)

All UniProt accessions (1): O94898

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell membrane. Cytoplasm.

Tissue specificity. Detected in all tissues analyzed.

Disease relevance. Urofacial syndrome 2 (UFS2) [MIM:615112] A rare autosomal recessive disorder characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of anatomical bladder outflow obstruction or overt neurological damage. Affected individuals often have reflux of infected urine from the bladder to the upper renal tract, with a risk of kidney damage and renal failure. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (2): NP_001299615, NP_055628* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000483	Cys-rich_flank_reg_C	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050467	LRFN	Family

Pfam: PF01463, PF07679, PF13855, PF13927

UniProt features (45 total): repeat 15, glycosylation site 12, domain 5, disulfide bond 3, topological domain 2, region of interest 2, compositionally biased region 2, signal peptide 1, chain 1, modified residue 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94898-F1	74.87	0.53

Functional residue map

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

Post-translational modifications (1): 906

Disulfide bonds (3): 519–580, 623–675, 717–766

Glycosylation sites (12): 91, 121, 173, 189, 274, 441, 468, 514, 571, 589, 687, 728

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 233 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, BROWNE_HCMV_INFECTION_6HR_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION_TO_CELL_SURFACE, GOBP_REGENERATION, GOBP_NEUROGENESIS, GOBP_RESPONSE_TO_AXON_INJURY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_LOCALIZATION_TO_CELL_SURFACE

GO Biological Process (11): membrane protein ectodomain proteolysis (GO:0006509), sensory perception of sound (GO:0007605), regulation of platelet-derived growth factor receptor signaling pathway (GO:0010640), protein localization to cell surface (GO:0034394), negative regulation of axon regeneration (GO:0048681), negative regulation of membrane protein ectodomain proteolysis (GO:0051045), innervation (GO:0060384), positive regulation of protein localization to cell surface (GO:2000010), regulation of neuron migration (GO:2001222), negative regulation of neuron projection development (GO:0010977), regulation of axon regeneration (GO:0048679)

GO Molecular Function (3): signaling receptor binding (GO:0005102), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (5): cytoplasm (GO:0005737), plasma membrane (GO:0005886), growth cone (GO:0030426), intracellular vesicle (GO:0097708), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
axon regeneration	2
intracellular anatomical structure	2
cellular anatomical structure	2
membrane protein proteolysis	1
sensory perception of mechanical stimulus	1
regulation of signal transduction	1
platelet-derived growth factor receptor signaling pathway	1
intracellular protein localization	1
negative regulation of response to external stimulus	1
regulation of axon regeneration	1
negative regulation of neuron projection regeneration	1
negative regulation of response to wounding	1
membrane protein ectodomain proteolysis	1
negative regulation of protein catabolic process	1
negative regulation of proteolysis	1
regulation of membrane protein ectodomain proteolysis	1
nerve development	1
multicellular organismal process	1
protein localization to cell surface	1
positive regulation of protein localization	1
regulation of protein localization to cell surface	1
neuron migration	1
regulation of cell migration	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
regulation of response to external stimulus	1
regulation of neuron projection regeneration	1
regulation of response to wounding	1
protein binding	1
molecular transducer activity	1
binding	1
membrane	1
cell periphery	1
site of polarized growth	1
distal axon	1
vesicle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1554 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRIG2	HPSE2	Q8WWQ2	719
LRIG2	ZNF490	Q9ULM2	474
LRIG2	RGMA	Q96B86	441
LRIG2	ANKLE2	Q86XL3	425
LRIG2	CNPY3	Q9BT09	420
LRIG2	OSBPL3	Q9H4L5	414
LRIG2	KLHL31	Q9H511	409
LRIG2	TDRD3	Q9H7E2	406
LRIG2	RACGAP1	Q9H0H5	401
LRIG2	PLK1	P53350	391
LRIG2	TINAG	Q9UJW2	388
LRIG2	ZBTB16	Q05516	381
LRIG2	SYDE2	Q5VT97	381
LRIG2	BIRC6	Q9NR09	381
LRIG2	RRM2	P31350	376

IntAct

54 interactions, top by confidence:

A	B	Type	Score
PDGFRB	LRIG2	psi-mi:“MI:0403”(colocalization)	0.560
PDGFRB	LRIG2	psi-mi:“MI:0915”(physical association)	0.560
LRIG1	LRIG2	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
SPSB2	ARHGEF10	psi-mi:“MI:0914”(association)	0.530
CNPY3	LRIG2	psi-mi:“MI:0914”(association)	0.530
SPSB4	ARHGEF10	psi-mi:“MI:0914”(association)	0.530
LRIG2	EGFR	psi-mi:“MI:0403”(colocalization)	0.460
LRIG2	EGFR	psi-mi:“MI:0915”(physical association)	0.460
ORF47	ZZEF1	psi-mi:“MI:0914”(association)	0.350
PON2	ENTPD6	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
TMEM106A	QSOX1	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
SPSB4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
COMTD1	TARS3	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-G	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (85): LRIG2 (Affinity Capture-MS), EGFR (Affinity Capture-Western), LRIG2 (Affinity Capture-MS), LRIG2 (Affinity Capture-MS), LRIG2 (Affinity Capture-MS), LRIG2 (Affinity Capture-MS), LRIG2 (Proximity Label-MS), LRIG2 (Proximity Label-MS), LRIG2 (Proximity Label-MS), LRIG2 (Proximity Label-MS), LRIG2 (Proximity Label-MS), LRIG2 (Proximity Label-MS), LRIG2 (Proximity Label-MS), LRIG2 (Proximity Label-MS), LRIG2 (Affinity Capture-MS)

ESM2 similar proteins: A0N0X6, A4IIW9, B0BLW3, B1H134, B1H234, B4F7C5, D3ZAL8, D3ZTV3, D4A7P2, E5DHB5, F1NUK7, F7D3V9, O43155, O43300, O94898, P58681, Q32Q07, Q3SXY7, Q3URE9, Q504C1, Q50L44, Q52KR2, Q5R482, Q5R6T0, Q5RDJ4, Q61809, Q66HV9, Q6RKD8, Q6UXK5, Q70AK3, Q7L985, Q80XG9, Q80ZD7, Q80ZD8, Q80ZD9, Q86VH4, Q86VH5, Q8BGA3, Q8BGT1, Q8BLU0

Diamond homologs: A0A087WV53, A2AAJ9, A2ASS6, A2RUH7, O75147, O94856, O94898, P05548, P52179, P54296, P97685, Q00872, Q23551, Q52KR2, Q5VST9, Q62234, Q80W87, Q810U3, Q8WX93, Q92626, A1KZ92, A2AJ76, A4IFW2, A4IGL7, A6NDA9, B0BNK7, B0V2N1, D2HFT7, D3YXG0, D4A1J9, D4ABX8, F1NWE3, G5EG78, O15146, O73775, O75325, P07722, P15364, P20916, P20917

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 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.

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	5	17.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	9
Uncertain significance	160
Likely benign	24
Benign	10

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
1072090	NC_000001.10:g.(?113636961)(113653184_?)del	Pathogenic
1074689	NM_014813.3(LRIG2):c.17del (p.Leu6fs)	Pathogenic
40206	NM_014813.3(LRIG2):c.1230del (p.Glu410fs)	Pathogenic
40207	NM_014813.3(LRIG2):c.2125C>T (p.Arg709Ter)	Pathogenic
40208	NM_014813.3(LRIG2):c.2088del (p.Ser697fs)	Pathogenic
40209	NM_014813.2(LRIG2):c.1980_1981insJX891452.1:g.1_371 (p.Ile662Phefs)	Pathogenic
4279327	GRCh37/hg19 1p13.2(chr1:113634705-113652592)x1	Pathogenic
977637	NM_014813.3(LRIG2):c.804-2A>C	Pathogenic
1065942	NM_014813.3(LRIG2):c.306-2A>G	Likely pathogenic
3911237	NM_014813.3(LRIG2):c.1091del (p.Thr363_Leu364insTer)	Likely pathogenic
4547402	NM_014813.3(LRIG2):c.85C>T (p.Gln29Ter)	Likely pathogenic
4845798	NM_014813.3(LRIG2):c.2530+1G>T	Likely pathogenic
4845891	NM_014813.3(LRIG2):c.2777_2795del (p.Glu926fs)	Likely pathogenic
4849332	NM_014813.3(LRIG2):c.524_527del (p.Ser175fs)	Likely pathogenic
562385	NM_014813.3(LRIG2):c.1237G>T (p.Glu413Ter)	Likely pathogenic
562386	NM_014813.3(LRIG2):c.1569C>A (p.Ser523Arg)	Likely pathogenic
666570	NM_014813.1(LRIG2):c.1799-2_1799-1delAG	Likely pathogenic

SpliceAI

3453 predictions. Top by Δscore:

Variant	Effect	Δscore
1:113073646:G:GG	donor_gain	1.0000
1:113091315:CAGG:C	acceptor_loss	1.0000
1:113091316:A:AG	acceptor_gain	1.0000
1:113091316:A:AT	acceptor_loss	1.0000
1:113091316:AG:A	acceptor_gain	1.0000
1:113091316:AGG:A	acceptor_gain	1.0000
1:113091317:G:GC	acceptor_loss	1.0000
1:113091317:G:GG	acceptor_gain	1.0000
1:113091317:GG:G	acceptor_gain	1.0000
1:113091317:GGG:G	acceptor_gain	1.0000
1:113091317:GGGA:G	acceptor_gain	1.0000
1:113091379:G:GT	donor_gain	1.0000
1:113091379:G:T	donor_gain	1.0000
1:113091379:GAAGT:G	donor_gain	1.0000
1:113091380:AAGT:A	donor_gain	1.0000
1:113091381:AGTG:A	donor_loss	1.0000
1:113091382:GT:G	donor_gain	1.0000
1:113091382:GTGT:G	donor_loss	1.0000
1:113091383:TGTA:T	donor_loss	1.0000
1:113091384:G:A	donor_loss	1.0000
1:113091384:G:GG	donor_gain	1.0000
1:113092178:G:T	donor_gain	1.0000
1:113093281:G:GG	donor_gain	1.0000
1:113093285:GTTA:G	donor_gain	1.0000
1:113093289:G:GG	donor_gain	1.0000
1:113093424:TTACA:T	acceptor_loss	1.0000
1:113093427:CA:C	acceptor_loss	1.0000
1:113093428:A:AC	acceptor_loss	1.0000
1:113093428:A:AG	acceptor_gain	1.0000
1:113093429:G:GG	acceptor_gain	1.0000

AlphaMissense

7029 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:113110363:G:C	W533C	1.000
1:113110363:G:T	W533C	1.000
1:113110496:T:G	Y578D	1.000
1:113112583:T:A	W635R	1.000
1:113112583:T:C	W635R	1.000
1:113112585:G:C	W635C	1.000
1:113112585:G:T	W635C	1.000
1:113112686:A:C	D669A	1.000
1:113112686:A:T	D669V	1.000
1:113112749:T:C	L690P	1.000
1:113114531:T:A	W729R	1.000
1:113114531:T:C	W729R	1.000
1:113114533:G:C	W729C	1.000
1:113114533:G:T	W729C	1.000
1:113093221:T:A	N107K	0.999
1:113093221:T:G	N107K	0.999
1:113093438:A:T	N130I	0.999
1:113093439:T:A	N130K	0.999
1:113093439:T:G	N130K	0.999
1:113093501:T:C	L151P	0.999
1:113093510:A:T	N154I	0.999
1:113093511:T:A	N154K	0.999
1:113093511:T:G	N154K	0.999
1:113093564:T:C	L172P	0.999
1:113098785:T:C	L391P	0.999
1:113110314:T:C	L517P	0.999
1:113110319:T:C	C519R	0.999
1:113110361:T:A	W533R	0.999
1:113110361:T:C	W533R	0.999
1:113110497:A:C	Y578S	0.999

dbSNP variants (sampled 300 via entrez): RS1000047446 (1:113108175 A>G), RS1000149355 (1:113114267 C>T), RS1000196153 (1:113080837 T>G), RS1000273635 (1:113100681 G>A), RS1000381463 (1:113127217 C>T), RS1000383253 (1:113087104 C>G,T), RS1000392300 (1:113120427 A>G), RS1000507364 (1:113072092 G>C), RS1000715453 (1:113125320 C>T), RS1000721587 (1:113088431 T>G), RS1000827168 (1:113100943 T>A), RS1000843665 (1:113126720 G>A), RS1000860816 (1:113083464 G>C), RS1000952064 (1:113081967 A>G), RS1000981602 (1:113088640 C>A)

Disease associations

OMIM: gene MIM:608869 | disease phenotypes: MIM:615112

GenCC curated gene-disease

Disease	Classification	Inheritance
urofacial syndrome 2	Strong	Autosomal recessive
Ochoa syndrome	Supportive	Autosomal recessive

Mondo (2): urofacial syndrome 2 (MONDO:0014049), Ochoa syndrome (MONDO:0000463)

Orphanet (1): Urofacial syndrome (Orphanet:2704)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000021	Megacystis
HP:0000028	Cryptorchidism
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000126	Hydronephrosis
HP:0000273	Facial grimacing
HP:0000796	Urethral obstruction
HP:0000805	Enuresis
HP:0000822	Hypertension
HP:0001959	Polydipsia
HP:0002019	Constipation
HP:0002607	Bowel incontinence
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0005340	Spastic/hyperactive bladder
HP:0011463	Childhood onset
HP:0032465	Bladder trabeculation

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST008477_26	Emphysema annual change measurement in smokers (adjusted lung density)	1.000000e-06
GCST009391_1762	Metabolite levels	4.000000e-06
GCST010002_392	Refractive error	8.000000e-20
GCST010396_129	Gut microbiota (bacterial taxa, hurdle binary method)	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007626	emphysema imaging measurement
EFO:0010370	lysophosphatidylethanolamine 20:4 measurement
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536480	Urofacial syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
Air Pollutants	affects expression, increases abundance, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
beta-lapachone	decreases expression	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
bisphenol S	increases methylation	1
Leflunomide	increases expression	1
Formaldehyde	decreases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression, increases abundance	1
Cyclosporine	increases expression	1
Levonorgestrel	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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