SIPA1L3

Summary

SIPA1L3 (signal induced proliferation associated 1 like 3, HGNC:23801) is a protein-coding gene on chromosome 19q13.13-q13.2, encoding Signal-induced proliferation-associated 1-like protein 3 (O60292). Plays a critical role in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization in the lens.

This gene belongs to the signal induced proliferation associated 1 family of genes, which encode GTPase-activating proteins specific for the GTP-binding protein Rap1. Rap1 has been implicated in regulation of cell adhesion, cell polarity, and organization of the cytoskeleton. Like other members of the family, the protein encoded by this gene contains RapGAP and PDZ domains. In addition, this protein contains a C-terminal leucine zipper domain. This gene is proposed to function in epithelial cell morphogenesis and establishment or maintenance of polarity. Consistently, expression of the protein in cell culture showed localization to cell-cell borders in apical regions, and downregulation of the gene in 3D Caco2 cell culture resulted in abnormal cell polarity and morphogenesis. Allelic variants of this gene have been associated with congenital cataracts in humans.

Source: NCBI Gene 23094 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cataract 45 (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 13
• Clinical variants (ClinVar): 602 total — 2 pathogenic
• Phenotypes (HPO): 2
• MANE Select transcript: NM_015073

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23801
Approved symbol	SIPA1L3
Name	signal induced proliferation associated 1 like 3
Location	19q13.13-q13.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0545, SPAR3
Ensembl gene	ENSG00000105738
Ensembl biotype	protein_coding
OMIM	616655
Entrez	23094

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 6 protein_coding, 5 retained_intron, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000222345, ENST00000476317, ENST00000594553, ENST00000595384, ENST00000595495, ENST00000595982, ENST00000596403, ENST00000599644, ENST00000600919, ENST00000601054, ENST00000601222, ENST00000601881, ENST00000911499, ENST00000911500, ENST00000911502, ENST00000911503

RefSeq mRNA: 1 — MANE Select: NM_015073 NM_015073

CCDS: CCDS33007

Canonical transcript exons

ENST00000222345 — 22 exons

Exon	Start	End
ENSE00000701079	38130498	38130772
ENSE00000701087	38142573	38142710
ENSE00000817773	38141184	38141435
ENSE00000817774	38119306	38119882
ENSE00001115154	38192145	38192310
ENSE00001115155	38193537	38193780
ENSE00001115156	38162253	38162371
ENSE00001115158	38198389	38198532
ENSE00001115159	38201862	38201997
ENSE00001115160	38164479	38164906
ENSE00001115161	38182519	38182740
ENSE00001115162	38152840	38152967
ENSE00001115163	38204127	38204208
ENSE00001241425	38101052	38101226
ENSE00001241435	38099962	38100150
ENSE00001262141	38081256	38083099
ENSE00001262158	38029089	38029156
ENSE00001262177	37907208	37907358
ENSE00001314762	38206097	38208369
ENSE00002244493	38110227	38110384
ENSE00002485513	38106537	38106640
ENSE00003623241	38088721	38088851

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 94.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.2539 / max 290.9527, expressed in 1795 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175581	23.4737	1792
175586	1.8345	466
175591	0.6650	258
175583	0.5116	241
175587	0.3110	170
175584	0.1203	49
175588	0.1007	48
175582	0.0880	31
175589	0.0772	37
175585	0.0548	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	94.09	gold quality
endometrium epithelium	UBERON:0004811	92.89	silver quality
islet of Langerhans	UBERON:0000006	91.61	gold quality
cerebellar vermis	UBERON:0004720	91.24	silver quality
parotid gland	UBERON:0001831	90.22	silver quality
duodenum	UBERON:0002114	90.07	gold quality
cardia of stomach	UBERON:0001162	89.79	gold quality
vena cava	UBERON:0004087	89.77	silver quality
superior surface of tongue	UBERON:0007371	89.60	gold quality
tongue squamous epithelium	UBERON:0006919	89.53	silver quality
medial globus pallidus	UBERON:0002477	89.45	gold quality
ileal mucosa	UBERON:0000331	89.33	gold quality
globus pallidus	UBERON:0001875	89.22	gold quality
pylorus	UBERON:0001166	89.04	silver quality
tongue	UBERON:0001723	88.92	silver quality
CA1 field of hippocampus	UBERON:0003881	88.86	silver quality
Brodmann (1909) area 10	UBERON:0013541	88.74	silver quality
body of tongue	UBERON:0011876	88.64	silver quality
ventral tegmental area	UBERON:0002691	88.41	silver quality
renal medulla	UBERON:0000362	88.30	gold quality
subthalamic nucleus	UBERON:0001906	88.12	silver quality
colonic epithelium	UBERON:0000397	88.08	gold quality
lateral globus pallidus	UBERON:0002476	87.71	silver quality
pharyngeal mucosa	UBERON:0000355	87.69	silver quality
nipple	UBERON:0002030	87.61	gold quality
inferior vagus X ganglion	UBERON:0005363	87.51	silver quality
lateral nuclear group of thalamus	UBERON:0002736	87.46	silver quality
rectum	UBERON:0001052	87.37	gold quality
dorsal plus ventral thalamus	UBERON:0001897	87.12	silver quality
pons	UBERON:0000988	87.08	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.91
E-MTAB-6058	no	96.78
E-MTAB-7303	no	46.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

109 targeting SIPA1L3, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
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-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548D-3P	99.87	70.67	4362

Literature-anchored findings (GeneRIF, showing 3)

• Whole-exome sequencing identified a homozygous nonsense variant in SIPA1L3 in two sisters with congenital cataract. (PMID:25804400)
• Abnormalities of SIPA1L3 contribute to lens and eye defects, and we identify a critical role for SIPA1L3 in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization. (PMID:26231217)
• smoking cessation benefited survival of LUAD patients with low methylation at cg02268510SIPA 1L3 . The results have implications for not only smoking cessation after diagnosis, but also possible methylation-specific drug targeting. (PMID:30924596)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sipa1l3	ENSDARG00000061699
mus_musculus	Sipa1l3	ENSMUSG00000030583
rattus_norvegicus	Sipa1l3	ENSRNOG00000020703
drosophila_melanogaster	RapGAP1	FBGN0264895
caenorhabditis_elegans		WBGENE00018734

Paralogs (6): RAP1GAP (ENSG00000076864), SIPA1L2 (ENSG00000116991), RAP1GAP2 (ENSG00000132359), GARNL3 (ENSG00000136895), SIPA1L1 (ENSG00000197555), SIPA1 (ENSG00000213445)

Protein

Protein identifiers

Signal-induced proliferation-associated 1-like protein 3 — O60292 (reviewed: O60292)

Alternative names: SPA-1-like protein 3

All UniProt accessions (3): O60292, M0QX89, M0R2Q7

UniProt curated annotations — full annotation on UniProt →

Function. Plays a critical role in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization in the lens.

Subcellular location. Apical cell membrane.

Disease relevance. A chromosomal translocation involving SIPA1L3 is found in a patient with bilateral severe ocular abnormalities including congenital cataracts, corneal clouding, iridocorneal and lenticular adhesions and microphthalmia. Chromosomal translocation t(2;19)(q37.3;q13.1). In addition to translocation, missense variant has been found in patient with bilateral congenital cataracts. Cataract 45 (CTRCT45) [MIM:616851] An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_055888* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000331	Rap/Ran_GAP_dom	Domain
IPR001478	PDZ	Domain
IPR021818	SIPA1L_C	Domain
IPR035974	Rap/Ran-GAP_sf	Homologous_superfamily
IPR036034	PDZ_sf	Homologous_superfamily
IPR050989	Rap1_Ran_GAP	Family

Pfam: PF00595, PF02145, PF11881, PF21022

UniProt features (42 total): compositionally biased region 15, modified residue 13, region of interest 7, sequence variant 3, domain 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60292-F1	56.37	0.24

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 (13): 100, 146, 401, 1364, 1387, 1448, 1544, 1547, 1619, 1622, 1677, 1699, 1703

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 164 (showing top): GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, MODULE_255, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_ESTABLISHMENT_OF_EPITHELIAL_CELL_POLARITY, ROVERSI_GLIOMA_COPY_NUMBER_UP, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, MODULE_317, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, KOYAMA_SEMA3B_TARGETS_UP, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_EPITHELIAL_CELL_MORPHOGENESIS, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOCC_CELL_CELL_JUNCTION

GO Biological Process (6): eye development (GO:0001654), hematopoietic progenitor cell differentiation (GO:0002244), epithelial cell morphogenesis (GO:0003382), cytoskeleton organization (GO:0007010), regulation of small GTPase mediated signal transduction (GO:0051056), establishment of epithelial cell polarity (GO:0090162)

GO Molecular Function (2): GTPase activator activity (GO:0005096), protein binding (GO:0005515)

GO Cellular Component (12): stress fiber (GO:0001725), obsolete extracellular space (GO:0005615), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), apical part of cell (GO:0045177), tricellular tight junction (GO:0061689), glutamatergic synapse (GO:0098978), postsynaptic specialization, intracellular component (GO:0099091), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
sensory organ development	1
visual system development	1
hemopoiesis	1
cell differentiation	1
cell morphogenesis	1
epithelial cell development	1
organelle organization	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
establishment of cell polarity	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
actomyosin	1
contractile actin filament bundle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
tight junction	1
synapse	1
intracellular membraneless organelle	1
postsynaptic specialization	1

Protein interactions and networks

STRING

866 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIPA1L3	C10orf71	Q711Q0	525
SIPA1L3	WDR87	Q6ZQQ6	476
SIPA1L3	PGBD1	Q96JS3	464
SIPA1L3	DKKL1	Q9UK85	429
SIPA1L3	GJA3	Q9Y6H8	427
SIPA1L3	KCNC3	Q14003	409
SIPA1L3	LIPN	Q5VXI9	408
SIPA1L3	ENOX1	Q8TC92	408
SIPA1L3	GJA8	P48165	405
SIPA1L3	DAGLA	Q9Y4D2	401
SIPA1L3	AKR1E2	Q96JD6	399
SIPA1L3	KBTBD2	Q8IY47	383
SIPA1L3	CRYBA4	P53673	382
SIPA1L3	CRYAA	P02489	378
SIPA1L3	DNMBP	Q6XZF7	375

IntAct

123 interactions, top by confidence:

A	B	Type	Score
YWHAZ	SIPA1L3	psi-mi:“MI:0915”(physical association)	0.790
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
Copa	COPE	psi-mi:“MI:0915”(physical association)	0.560
SFN	SIPA1L3	psi-mi:“MI:0915”(physical association)	0.540
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
WDR83	SH2B2	psi-mi:“MI:0914”(association)	0.530
LZTS2	UNC119B	psi-mi:“MI:0914”(association)	0.530
DYRK1B	BMAL1	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
SIPA1L3	E6	psi-mi:“MI:0407”(direct interaction)	0.440
SIPA1L3	ABCC4	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF16	SIPA1L3	psi-mi:“MI:0407”(direct interaction)	0.440
ASIC3	SIPA1L3	psi-mi:“MI:0407”(direct interaction)	0.440
ATP2B4	SIPA1L3	psi-mi:“MI:0407”(direct interaction)	0.440
SIPA1L3	CYSLTR2	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	SIPA1L3	psi-mi:“MI:0407”(direct interaction)	0.440
DGKZ	SIPA1L3	psi-mi:“MI:0407”(direct interaction)	0.440
DOCK4	SIPA1L3	psi-mi:“MI:0407”(direct interaction)	0.440
SIPA1L3	FRMPD4	psi-mi:“MI:0407”(direct interaction)	0.440
FZD7	SIPA1L3	psi-mi:“MI:0407”(direct interaction)	0.440
TAMALIN	SIPA1L3	psi-mi:“MI:0407”(direct interaction)	0.440
E6	SIPA1L3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (160): SIPA1L3 (Affinity Capture-MS), SIPA1L3 (Biochemical Activity), SIPA1L3 (Proximity Label-MS), SIPA1L3 (Proximity Label-MS), SIPA1L3 (Proximity Label-MS), SIPA1L3 (Proximity Label-MS), SIPA1L3 (Proximity Label-MS), SIPA1L3 (Affinity Capture-MS), SIPA1L3 (Affinity Capture-MS), SIPA1L3 (Affinity Capture-MS), SIPA1L3 (Affinity Capture-MS), SIPA1L3 (Affinity Capture-MS), SIPA1L3 (Affinity Capture-MS), SIPA1L3 (Affinity Capture-MS), SIPA1L3 (Affinity Capture-MS)

ESM2 similar proteins: A1Z7A6, A2ALS5, A5PF44, A7KAX9, A8E7C5, A8JQ65, B3LXF2, B3NYS4, B4I4Y1, B4JHJ7, B4K6T8, B4PRE2, B4R0A5, G3X9J0, G5EFI8, O35412, O35711, O43166, O60292, P43125, P47736, Q14693, Q22744, Q2NKQ1, Q2PE14, Q3V0G7, Q4P3S3, Q5JCS6, Q5SVL6, Q5VVW2, Q5ZJY3, Q5ZMV8, Q684P5, Q80TE4, Q811P8, Q8BPQ7, Q8C0T5, Q8C8U0, Q8CDA1, Q91ZP3

Diamond homologs: A2ALS5, A5PF44, G3X9J0, O35412, O43166, O60292, P46062, P47736, P49815, P49816, Q3V0G7, Q54EH3, Q55AN8, Q5JCS6, Q5SVL6, Q5VVW2, Q5ZJY3, Q5ZMV8, Q61037, Q684P5, Q75J96, Q80TE4, Q8C0T5, Q96FS4, Q9P2F8, Q2PPJ7, Q9UUG9, A3KGS3, P86411, Q6GYQ0, Q8BUL6, Q9HB21, Q54TK4, Q9VB98, O55007, Q6GYP7, Q54SS8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 118 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	70.7×	3e-11
Activation of BAD and translocation to mitochondria	7	70.1×	3e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	61.9×	7e-10
Activation of BH3-only proteins	7	45.7×	5e-09
RHO GTPases activate PKNs	9	37.6×	2e-10
Intrinsic Pathway for Apoptosis	7	27.0×	2e-07
FOXO-mediated transcription	5	22.1×	5e-05
Translocation of SLC2A4 (GLUT4) to the plasma membrane	10	20.3×	4e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	22.4×	2e-04
intracellular protein localization	9	9.6×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	375
Likely benign	106
Benign	78

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1687350	NM_015073.3(SIPA1L3):c.3492dup (p.Gly1165fs)	Pathogenic
223242	NM_015073.3(SIPA1L3):c.4489C>T (p.Arg1497Ter)	Pathogenic

SpliceAI

6556 predictions. Top by Δscore:

Variant	Effect	Δscore
19:37907359:G:GG	donor_gain	1.0000
19:37907359:GTAC:G	donor_loss	1.0000
19:37907360:T:G	donor_loss	1.0000
19:38088715:TCTTA:T	acceptor_loss	1.0000
19:38088716:CTTA:C	acceptor_loss	1.0000
19:38088717:TTAGA:T	acceptor_loss	1.0000
19:38088718:TAGAA:T	acceptor_loss	1.0000
19:38088719:A:AG	acceptor_gain	1.0000
19:38088719:A:G	acceptor_loss	1.0000
19:38088720:G:GG	acceptor_gain	1.0000
19:38088720:G:T	acceptor_loss	1.0000
19:38088720:GA:G	acceptor_gain	1.0000
19:38088720:GAA:G	acceptor_gain	1.0000
19:38088720:GAAC:G	acceptor_gain	1.0000
19:38088720:GAACA:G	acceptor_gain	1.0000
19:38088847:GCGAG:G	donor_gain	1.0000
19:38088849:GAG:G	donor_gain	1.0000
19:38088850:AG:A	donor_gain	1.0000
19:38088851:GG:G	donor_gain	1.0000
19:38088851:GGTA:G	donor_loss	1.0000
19:38088852:G:C	donor_loss	1.0000
19:38088852:G:GG	donor_gain	1.0000
19:38099959:TAG:T	acceptor_loss	1.0000
19:38099960:A:AG	acceptor_gain	1.0000
19:38099960:A:C	acceptor_loss	1.0000
19:38099961:G:GG	acceptor_gain	1.0000
19:38099961:GC:G	acceptor_gain	1.0000
19:38099961:GCTC:G	acceptor_gain	1.0000
19:38100147:AGGG:A	donor_gain	1.0000
19:38100148:GGG:G	donor_gain	1.0000

AlphaMissense

11647 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:38088771:A:C	S529R	1.000
19:38088773:C:A	S529R	1.000
19:38088773:C:G	S529R	1.000
19:38106549:G:A	G681E	1.000
19:38106596:C:G	H697D	1.000
19:38110238:G:C	K715N	1.000
19:38110238:G:T	K715N	1.000
19:38110240:G:C	R716T	1.000
19:38110240:G:T	R716M	1.000
19:38110241:G:C	R716S	1.000
19:38110241:G:T	R716S	1.000
19:38110249:G:A	G719E	1.000
19:38110253:T:A	N720K	1.000
19:38110253:T:G	N720K	1.000
19:38110255:A:C	D721A	1.000
19:38110255:A:T	D721V	1.000
19:38119497:T:C	L828P	1.000
19:38119554:T:A	I847N	1.000
19:38119767:G:A	G918D	1.000
19:38119769:T:A	W919R	1.000
19:38119769:T:C	W919R	1.000
19:38130535:T:A	L969H	1.000
19:38130535:T:C	L969P	1.000
19:38130540:C:G	R971G	1.000
19:38130541:G:C	R971P	1.000
19:38130541:G:T	R971L	1.000
19:38130543:A:T	N972Y	1.000
19:38130544:A:T	N972I	1.000
19:38130545:C:A	N972K	1.000
19:38130545:C:G	N972K	1.000

dbSNP variants (sampled 300 via entrez): RS1000000426 (19:38069600 C>T), RS1000002461 (19:38101896 C>T), RS1000022875 (19:38150244 G>A), RS1000023629 (19:37905867 G>C,T), RS1000026355 (19:37981786 A>G), RS1000028795 (19:38100753 G>A), RS1000030509 (19:37941750 C>T), RS1000039237 (19:38109114 G>A), RS1000043806 (19:37982149 G>A), RS1000054348 (19:38021877 G>T), RS1000054926 (19:38056045 T>C), RS1000065026 (19:37994069 A>C,G), RS1000083961 (19:37941374 T>C), RS1000094908 (19:38069399 A>C,G), RS1000120029 (19:38138178 A>C)

Disease associations

OMIM: gene MIM:616655 | disease phenotypes: MIM:616851

GenCC curated gene-disease

Disease	Classification	Inheritance
cataract 45	Moderate	Autosomal dominant
total early-onset cataract	Supportive	Autosomal dominant

Mondo (3): cataract 45 (MONDO:0014799), breast ductal adenocarcinoma (MONDO:0005590), total early-onset cataract (MONDO:0021548)

Orphanet (1): Early onset non-syndromic cataract (Orphanet:91492)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000519	Developmental cataract

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST003372_39	Glomerular filtration rate (creatinine)	4.000000e-08
GCST003875_23	Gut microbiota (bacterial taxa)	1.000000e-09
GCST004292_57	Glomerular filtration rate (creatinine)	2.000000e-06
GCST007876_147	Estimated glomerular filtration rate	5.000000e-08
GCST007916_5	Hyperuricemia	2.000000e-16
GCST007917_6	Estimated glomerular filtration rate	2.000000e-16
GCST007918_6	Serum uric acid levels	2.000000e-16
GCST007919_14	Creatinine levels	2.000000e-16
GCST007920_15	Chronic kidney disease	2.000000e-16
GCST008745_25	Estimated glomerular filtration rate in non-diabetics	4.000000e-11
GCST008747_90	Estimated glomerular filtration rate	5.000000e-24
GCST008891_22	Cognitive performance (processing speed)	6.000000e-06
GCST90013407_167	Liver enzyme levels (gamma-glutamyl transferase)	1.000000e-13

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0007883	taxonomic microbiome measurement
EFO:0009104	hyperuricemia
EFO:0004761	uric acid measurement
EFO:0004363	information processing speed
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, increases expression, affects cotreatment, decreases expression, affects expression	5
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases methylation	4
Estradiol	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
potassium perchlorate	decreases expression	1
titanium dioxide	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	affects methylation	1
coumarin	decreases phosphorylation	1
vanadyl sulfate	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT06068348	Not specified	ACTIVE_NOT_RECRUITING	Liquid Biopsy Collection Study
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery