SIPA1

Summary

SIPA1 (signal-induced proliferation-associated 1, HGNC:10885) is a protein-coding gene on chromosome 11q13.1, encoding Signal-induced proliferation-associated protein 1 (Q96FS4). GTPase activator for the nuclear Ras-related regulatory proteins Rap1 and Rap2 in vitro, converting them to the putatively inactive GDP-bound state.

The product of this gene is a mitogen induced GTPase activating protein (GAP). It exhibits a specific GAP activity for Ras-related regulatory proteins Rap1 and Rap2, but not for Ran or other small GTPases. This protein may also hamper mitogen-induced cell cycle progression when abnormally or prematurely expressed. It is localized to the perinuclear region. Two alternatively spliced variants encoding the same isoform have been characterized to date.

Source: NCBI Gene 6494 — RefSeq curated summary.

At a glance

• GWAS associations: 29
• Clinical variants (ClinVar): 200 total
• Phenotypes (HPO): 2
• MANE Select transcript: NM_006747

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10885
Approved symbol	SIPA1
Name	signal-induced proliferation-associated 1
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	SPA1
Ensembl gene	ENSG00000213445
Ensembl biotype	protein_coding
OMIM	602180
Entrez	6494

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 27 protein_coding, 5 retained_intron

ENST00000394224, ENST00000526137, ENST00000527525, ENST00000528699, ENST00000529725, ENST00000530226, ENST00000531339, ENST00000533361, ENST00000534313, ENST00000534406, ENST00000871954, ENST00000871955, ENST00000871956, ENST00000871957, ENST00000871958, ENST00000871959, ENST00000871960, ENST00000871961, ENST00000871962, ENST00000871963, ENST00000871964, ENST00000871965, ENST00000926387, ENST00000926388, ENST00000926389, ENST00000969241, ENST00000969242, ENST00000969243, ENST00000969244, ENST00000969245, ENST00000969246, ENST00000969247

RefSeq mRNA: 2 — MANE Select: NM_006747 NM_006747, NM_153253

CCDS: CCDS8108

Canonical transcript exons

ENST00000534313 — 16 exons

Exon	Start	End
ENSE00001191269	65649561	65649672
ENSE00001191276	65649262	65649480
ENSE00001191285	65647384	65647658
ENSE00001191291	65646456	65647065
ENSE00001191319	65644955	65645129
ENSE00001191330	65642463	65642639
ENSE00001191339	65642250	65642377
ENSE00002140439	65638101	65638182
ENSE00002166549	65650569	65650912
ENSE00002167002	65640831	65641600
ENSE00002432559	65645854	65645957
ENSE00003474667	65649950	65650051
ENSE00003529021	65649757	65649865
ENSE00003530718	65646221	65646378
ENSE00003647982	65650138	65650192
ENSE00003678382	65650401	65650479

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 98.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.1995 / max 480.1222, expressed in 1797 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115186	16.0498	1701
115194	2.7521	768
115192	1.6536	301
115191	1.0891	113
115190	0.7702	111
115189	0.5432	103
115195	0.2917	176
115188	0.0497	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.86	gold quality
spleen	UBERON:0002106	97.07	gold quality
lower esophagus mucosa	UBERON:0035834	96.21	gold quality
apex of heart	UBERON:0002098	95.80	gold quality
upper lobe of left lung	UBERON:0008952	95.66	gold quality
sural nerve	UBERON:0015488	95.62	gold quality
tibial nerve	UBERON:0001323	95.61	gold quality
right lung	UBERON:0002167	95.33	gold quality
monocyte	CL:0000576	95.03	gold quality
leukocyte	CL:0000738	94.98	gold quality
blood	UBERON:0000178	94.80	gold quality
mononuclear cell	CL:0000842	94.69	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.31	gold quality
upper lobe of lung	UBERON:0008948	94.04	gold quality
right lobe of liver	UBERON:0001114	93.89	gold quality
left uterine tube	UBERON:0001303	93.65	gold quality
mucosa of transverse colon	UBERON:0004991	93.44	gold quality
metanephros cortex	UBERON:0010533	93.36	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.02	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.00	gold quality
lymph node	UBERON:0000029	92.95	gold quality
lower esophagus	UBERON:0013473	92.94	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.93	gold quality
right coronary artery	UBERON:0001625	92.92	gold quality
right adrenal gland	UBERON:0001233	92.70	gold quality
endocervix	UBERON:0000458	92.69	gold quality
omental fat pad	UBERON:0010414	92.62	gold quality
ectocervix	UBERON:0012249	92.53	gold quality
peritoneum	UBERON:0002358	92.51	gold quality
vermiform appendix	UBERON:0001154	92.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	714.43
E-MTAB-7381	no	117.57
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting SIPA1, 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-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-3936	97.64	64.47	732

Literature-anchored findings (GeneRIF, showing 22)

• role in regulating phorbol 12-myristate 13-acetate-stimulated but not ligand-induced beta 1 integrin-dependent leukocyte adhesion (PMID:12091396)
• Data identif a Rap GTPase-activating protein, signal-induced proliferation-associated protein 1 (SPA-1), as a factor that interacts with Brd4. (PMID:15456879)
• SIPA1 germline polymorphisms are associated with aggressive disease behavior in breast cancer. (PMID:16563182)
• SPA1 regulates the maintenance and differentiation of embryonic stem cells. (PMID:18033671)
• it is unlikely that SIPA1 plays a pathogenetic role in the development of juvenile myelomonocytic leukemia (PMID:18492118)
• Our results do not support a relationship between SIPA1 polymorphisms and breast cancer risk or subsequent survival (PMID:19089925)
• SIPA1 SNP rs3741378 was associated with increased breast cancer incidence. (PMID:19765277)
• In this case-control study, SNPs in SIPA1 varied statistically in cervical cancer patients with and without nodal metastases and in MMP9 after controlling for stage and lymphvascular space invasion. (PMID:19906411)
• SIPA1 expression is increased in human colorectal cancer. (PMID:22990111)
• Patients with metastatic breast cancer with SIPA1 545 T/T genotype had a significantly worse overall survival than did patients with C/T or C/C genotype (50.0% vs. 62.9%, P = 0.042). (PMID:23358895)
• Polymorphism in Sipa1 promoter gene is associated with lung cancer. (PMID:23661532)
• SIPA1 SNPs, rs746429 and rs2306364, were associated with decreased risk of triple-negative breast tumors. (PMID:23771732)
• This meta-analysis suggests that rs746429 is associated with the risk of breast cancer. (PMID:24006220)
• BRD4 short isoform interacts with RRP1B, SIPA1 and components of the LINC complex at the inner face of the nuclear membrane. (PMID:24260471)
• nuclear SIPA1 contributes to breast cancer cell invasion through the regulation of integrin beta1 signaling. (PMID:24704834)
• Our results indicate, for the first time, that the SIPA1 -313A>G may have a prognostic role in unresected NSCLC making it a potential predictor of poor survival due to earlier progression. (PMID:25352027)
• results suggest that SIPA1 and RRP1B germline polymorphisms are important for breast cancer prognosis (PMID:26901824)
• SIPA1 promotes oral squamous cell carcinoma metastasis by regulating the ITGB1 and MMP7. (PMID:28237246)
• Study shows that SIPA1 mRNA and protein expression are down-regulated in gastric cancer cells and correlate with tumor grading, invasion and lymph node metastasis as well as higher expression of VEGFA. Low SIPA1 levels in gastric cancer may then accelerate tumor development and progression by promoting VEGFA expression to increase vascular density. (PMID:28362978)
• SIPA1 enhances SMAD2/3 expression to maintain stem cell features in breast cancer cells. (PMID:33296812)
• A novel nuclear localization region in SIPA1 determines protein nuclear distribution and epirubicin-sensitivity of breast cancer cells. (PMID:33753200)
• A novel transcription factor SIPA1: identification and verification in triple-negative breast cancer. (PMID:37500797)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sipa1	ENSDARG00000076697
mus_musculus	Sipa1	ENSMUSG00000056917
rattus_norvegicus	Sipa1	ENSRNOG00000020726
drosophila_melanogaster	RapGAP1	FBGN0264895
caenorhabditis_elegans		WBGENE00018734

Paralogs (6): RAP1GAP (ENSG00000076864), SIPA1L3 (ENSG00000105738), SIPA1L2 (ENSG00000116991), RAP1GAP2 (ENSG00000132359), GARNL3 (ENSG00000136895), SIPA1L1 (ENSG00000197555)

Protein

Protein identifiers

Signal-induced proliferation-associated protein 1 — Q96FS4 (reviewed: Q96FS4)

Alternative names: GTPase-activating protein Spa-1, p130 SPA-1

All UniProt accessions (3): E9PIB3, Q96FS4, F6RY50

UniProt curated annotations — full annotation on UniProt →

Function. GTPase activator for the nuclear Ras-related regulatory proteins Rap1 and Rap2 in vitro, converting them to the putatively inactive GDP-bound state. Affects cell cycle progression.

Subunit / interactions. Interacts with RRP1B; the interaction leads to inhibition of SIPA1 GTPase activity.

Subcellular location. Nucleus. Cytoplasm. Perinuclear region. Endomembrane system.

Tissue specificity. Expressed in fetal as well as in adult tissues. Expressed abundantly in the lymphoid tissues such as thymus, spleen and peripheral blood lymphocytes and also shows a significant expression in the spinal cord.

Induction. Repressed by 12-O-tetradecanoylphorbol-13-acetate (TPA) in promyelocytic HL-60 cells.

RefSeq proteins (2): NP_006738, NP_694985 (=MANE)

Domains & families (InterPro)

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

Pfam: PF00595, PF02145, PF21022

UniProt features (32 total): sequence conflict 9, modified residue 8, sequence variant 4, region of interest 4, compositionally biased region 3, domain 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96FS4-F1	72.20	0.45

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 (8): 64, 67, 182, 304, 314, 817, 839, 912

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-392517	Rap1 signalling
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 244 (showing top): MYOGENIN_Q6, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_ACID_CHEMICAL, GCANCTGNY_MYOD_Q6, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, MODULE_45, GOBP_GROWTH, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, AREB6_01, GOBP_CELLULAR_RESPONSE_TO_ACID_CHEMICAL, AAAYRNCTG_UNKNOWN, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, chr11q13, SP1_Q2_01, SRF_C

GO Biological Process (9): adaptive immune response (GO:0002250), cytoskeleton organization (GO:0007010), negative regulation of cell adhesion (GO:0007162), signal transduction (GO:0007165), negative regulation of cell growth (GO:0030308), intracellular signal transduction (GO:0035556), cellular response to water deprivation (GO:0042631), negative regulation of cell cycle (GO:0045786), regulation of small GTPase mediated signal transduction (GO:0051056)

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

GO Cellular Component (7): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), endomembrane system (GO:0012505), protein-containing complex (GO:0032991), perinuclear region of cytoplasm (GO:0048471), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
negative regulation of cellular process	3
intracellular anatomical structure	2
cytoplasm	2
immune response	1
organelle organization	1
cell adhesion	1
regulation of cell adhesion	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
signal transduction	1
response to water deprivation	1
cellular response to stress	1
cellular response to water stimulus	1
cell cycle	1
regulation of cell cycle	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
vacuole	1
plasma membrane	1
cellular_component	1

Protein interactions and networks

STRING

1224 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIPA1	RRP1B	Q14684	769
SIPA1	RAP2A	P10114	705
SIPA1	AFDN	P55196	661
SIPA1	BRD4	O60885	658
SIPA1	RASA1	P20936	638
SIPA1	PTPN11	Q06124	615
SIPA1	AQP2	P41181	608
SIPA1	RRP1	P56182	515
SIPA1	ARHGAP26	Q9UNA1	495
SIPA1	NRAS	P01111	435
SIPA1	DPF2	Q92785	431
SIPA1	MUS81	Q96NY9	426
SIPA1	EXOC6B	Q9Y2D4	425
SIPA1	PTPRC	P08575	423
SIPA1	SNX32	Q86XE0	420

IntAct

198 interactions, top by confidence:

A	B	Type	Score
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
SIPA1	SIPA1L2	psi-mi:“MI:0407”(direct interaction)	0.590
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
LZTS2	UNC119B	psi-mi:“MI:0914”(association)	0.530
CDKN1A	SIPA1	psi-mi:“MI:0915”(physical association)	0.510
SIPA1	CDKN1A	psi-mi:“MI:0915”(physical association)	0.510
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
SIPA1	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
SIPA1	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
SIPA1	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC4	SIPA1	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF16	SIPA1	psi-mi:“MI:0407”(direct interaction)	0.440
ASIC3	SIPA1	psi-mi:“MI:0407”(direct interaction)	0.440
ATP2B4	SIPA1	psi-mi:“MI:0407”(direct interaction)	0.440
CYSLTR2	SIPA1	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	SIPA1	psi-mi:“MI:0407”(direct interaction)	0.440
DGKZ	SIPA1	psi-mi:“MI:0407”(direct interaction)	0.440
DOCK4	SIPA1	psi-mi:“MI:0407”(direct interaction)	0.440
FRMPD4	SIPA1	psi-mi:“MI:0407”(direct interaction)	0.440
SIPA1	FZD7	psi-mi:“MI:0407”(direct interaction)	0.440
TAMALIN	SIPA1	psi-mi:“MI:0407”(direct interaction)	0.440
E6	SIPA1	psi-mi:“MI:0407”(direct interaction)	0.440
ORF putative E6	SIPA1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	SIPA1	psi-mi:“MI:0407”(direct interaction)	0.440
KIR3DL3	SIPA1	psi-mi:“MI:0407”(direct interaction)	0.440
MAP2K2	SIPA1	psi-mi:“MI:0407”(direct interaction)	0.440
PBK	SIPA1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (52): SIPA1 (Affinity Capture-MS), SIPA1 (Affinity Capture-MS), SIPA1 (Affinity Capture-MS), SIPA1 (Affinity Capture-MS), SIPA1 (Affinity Capture-MS), SIPA1 (Affinity Capture-MS), SIPA1 (Affinity Capture-MS), SIPA1 (Affinity Capture-MS), SIPA1 (Affinity Capture-MS), SIPA1 (Affinity Capture-MS), SIPA1 (Affinity Capture-MS), SIPA1 (Affinity Capture-MS), SIPA1 (Affinity Capture-MS), SIPA1 (Affinity Capture-RNA), SIPA1 (Affinity Capture-MS)

ESM2 similar proteins: A1YF56, A2AEV7, A6NCS4, A7Y7W2, D3ZJK7, E1BEA8, F1MUS9, O15534, O35973, O43435, O43638, O60248, O75333, O77728, O94983, O95935, O95947, P22736, P46099, P51666, P56261, P57082, P70325, P70327, Q03484, Q0V8F0, Q15744, Q497V6, Q5DTT2, Q61660, Q61663, Q63HR2, Q64731, Q66JL1, Q6PZD9, Q6ZQN5, Q80Y50, Q810F8, Q861Q9, Q8AV66

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, Q8BUL6, Q9HB21, Q54TK4, Q9VB98, Q54SS8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 151 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
Activation of BAD and translocation to mitochondria	5	39.2×	7e-06
Ras activation upon Ca2+ influx through NMDA receptor	6	35.3×	1e-06
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	34.6×	1e-05
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	34.6×	1e-05
Unblocking of NMDA receptors, glutamate binding and activation	5	28.0×	3e-05
Negative regulation of NMDA receptor-mediated neuronal transmission	5	28.0×	3e-05
RHO GTPases activate PKNs	8	26.2×	9e-08
Activation of BH3-only proteins	5	25.6×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	48.1×	1e-13
receptor clustering	8	37.5×	1e-08
protein localization to synapse	6	34.6×	3e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	7	26.1×	2e-06
protein targeting	6	16.5×	1e-04
regulation of small GTPase mediated signal transduction	9	9.8×	4e-05
protein-containing complex assembly	10	8.6×	3e-05
cell-cell adhesion	10	7.6×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	157
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2341 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65642239:C:CA	acceptor_gain	1.0000
11:65642248:A:AG	acceptor_gain	1.0000
11:65642249:G:GG	acceptor_gain	1.0000
11:65642637:GTG:G	donor_gain	1.0000
11:65644947:A:AG	acceptor_gain	1.0000
11:65644948:C:G	acceptor_gain	1.0000
11:65644951:ACAG:A	acceptor_loss	1.0000
11:65644952:C:G	acceptor_gain	1.0000
11:65644952:CA:C	acceptor_loss	1.0000
11:65644953:A:AG	acceptor_gain	1.0000
11:65644953:AGCT:A	acceptor_gain	1.0000
11:65644954:G:GT	acceptor_gain	1.0000
11:65644954:GC:G	acceptor_gain	1.0000
11:65644954:GCT:G	acceptor_gain	1.0000
11:65644954:GCTG:G	acceptor_gain	1.0000
11:65644954:GCTGA:G	acceptor_gain	1.0000
11:65645094:GCTT:G	donor_gain	1.0000
11:65645130:G:GG	donor_gain	1.0000
11:65645829:T:TA	acceptor_gain	1.0000
11:65645831:T:TA	acceptor_gain	1.0000
11:65645838:A:AG	acceptor_gain	1.0000
11:65645839:A:G	acceptor_gain	1.0000
11:65645845:T:TA	acceptor_gain	1.0000
11:65646219:A:AG	acceptor_gain	1.0000
11:65646220:G:GG	acceptor_gain	1.0000
11:65646451:CGCAG:C	acceptor_loss	1.0000
11:65646452:GCAGG:G	acceptor_loss	1.0000
11:65646453:CAGGG:C	acceptor_loss	1.0000
11:65646454:A:AG	acceptor_gain	1.0000
11:65646454:A:C	acceptor_loss	1.0000

AlphaMissense

6626 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:65642300:A:C	S244R	1.000
11:65642302:C:A	S244R	1.000
11:65642302:C:G	S244R	1.000
11:65644972:G:C	K334N	1.000
11:65644972:G:T	K334N	1.000
11:65645911:T:C	F406S	1.000
11:65645913:C:G	H407D	1.000
11:65646232:G:C	K425N	1.000
11:65646232:G:T	K425N	1.000
11:65646249:A:C	D431A	1.000
11:65646249:A:T	D431V	1.000
11:65646267:T:C	F437S	1.000
11:65641576:T:G	Y219D	0.999
11:65641588:T:C	F223L	0.999
11:65641589:T:C	F223S	0.999
11:65641590:C:A	F223L	0.999
11:65641590:C:G	F223L	0.999
11:65642260:C:A	N230K	0.999
11:65642260:C:G	N230K	0.999
11:65642268:G:A	G233E	0.999
11:65642294:G:C	A242P	0.999
11:65642295:C:A	A242E	0.999
11:65642355:G:C	R262P	0.999
11:65642617:T:C	L321P	0.999
11:65642626:T:C	L324P	0.999
11:65642628:G:C	D325H	0.999
11:65642629:A:T	D325V	0.999
11:65644970:A:G	K334E	0.999
11:65645058:T:C	F363S	0.999
11:65645073:G:T	G368V	0.999

dbSNP variants (sampled 300 via entrez): RS1000581449 (11:65649197 T>C,G), RS1000713922 (11:65647355 C>G,T), RS1000744800 (11:65647589 A>G), RS1001329028 (11:65645725 G>A), RS1001481748 (11:65639403 C>T), RS1001547843 (11:65636807 C>T), RS1001598946 (11:65639587 G>A), RS1001941656 (11:65650950 A>C), RS1001957789 (11:65647869 TCTCTC>T), RS1002031113 (11:65648159 C>G), RS1002555452 (11:65638043 C>A,T), RS1003037639 (11:65637130 C>A,G,T), RS1003156753 (11:65643668 G>A,C), RS1003683704 (11:65648053 A>G), RS1003735869 (11:65648248 C>T)

Disease associations

OMIM: gene MIM:602180 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): esophageal atresia (MONDO:0001044), pyloric stenosis (MONDO:0001561)

Orphanet (0):

HPO phenotypes

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

HPO	Term
HP:0002032	Esophageal atresia
HP:0002021	Pyloric stenosis

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST002481_8	Acne (severe)	3.000000e-11
GCST004603_61	Platelet count	5.000000e-14
GCST006166_10	Diastolic blood pressure x alcohol consumption interaction (2df test)	2.000000e-16
GCST006167_9	Mean arterial pressure x alcohol consumption interaction (2df test)	8.000000e-09
GCST006169_18	Diastolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	1.000000e-10
GCST006170_39	Systolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	2.000000e-10
GCST006172_2	Mean arterial pressure x alcohol consumption (light vs heavy) interaction (2df test)	3.000000e-11
GCST006187_34	Diastolic blood pressure (cigarette smoking interaction)	1.000000e-09
GCST006188_39	Systolic blood pressure (cigarette smoking interaction)	8.000000e-15
GCST006259_5	Systolic blood pressure	8.000000e-09
GCST006434_31	Systolic blood pressure x alcohol consumption interaction (2df test)	4.000000e-17
GCST006434_9	Systolic blood pressure x alcohol consumption interaction (2df test)	1.000000e-20
GCST006611_134	HDL cholesterol	5.000000e-10
GCST007094_13	Diastolic blood pressure	8.000000e-06
GCST007099_95	Systolic blood pressure	7.000000e-08
GCST007267_301	Systolic blood pressure	5.000000e-17
GCST007269_203	Pulse pressure	3.000000e-08
GCST007930_113	Medication use (agents acting on the renin-angiotensin system)	1.000000e-13
GCST008916_61	Asthma	4.000000e-11
GCST009602_61	Metabolic syndrome	3.000000e-09
GCST010867_1	Coronary artery disease	9.000000e-10
GCST90002404_516	Red cell distribution width	8.000000e-34
GCST90002405_284	Reticulocyte count	4.000000e-15
GCST90002406_371	Reticulocyte fraction of red cells	8.000000e-13
GCST90020024_393	A body shape index	2.000000e-10
GCST90020025_1878	Waist-to-hip ratio adjusted for BMI	4.000000e-10
GCST90020027_1495	Waist-hip index	3.000000e-10
GCST90020028_1997	Hip circumference adjusted for BMI	3.000000e-08
GCST90020029_327	Waist circumference adjusted for body mass index	2.000000e-11

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004329	alcohol drinking
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0006335	systolic blood pressure
EFO:0006527	smoking status measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0005763	pulse pressure measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0000195	metabolic syndrome
EFO:0009188	Red cell distribution width
EFO:0007986	reticulocyte count
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D004933	Esophageal Atresia	C06.198.330; C06.405.117.260; C16.131.314.330
D017219	Gastric Outlet Obstruction	C06.405.748.340
D011707	Pyloric Stenosis	C06.405.748.340.690

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases oxidation, affects expression, affects cotreatment	3
Ozone	affects cotreatment, decreases expression, increases oxidation, increases abundance, affects expression	2
Tretinoin	increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
bis(tri-n-butyltin)oxide	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
tamibarotene	increases expression	1
2-palmitoylglycerol	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
Benzene	increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Ivermectin	decreases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2FE	Abcam HeLa SIPA1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00556283	PHASE4	COMPLETED	RCT: STARR vs Biofeedback
NCT00226044	PHASE3	COMPLETED	Rectal and Oral Omeprazole Treatment of Reflux Disease in Infants.
NCT03127345	PHASE2	WITHDRAWN	Omega 3 Fatty Acid Treatment for Pediatric Musculoskeletal Health
NCT02033772	Not specified	COMPLETED	Prospective Data Collection of Patients < 6 Months of Age Undergoing Thoracoscopic Surgery
NCT02466451	Not specified	COMPLETED	Study in Children With the Diagnosis of Congenital Diaphragmatic Hernia (CDH) and Oesophageal Atresia (EA)
NCT02525705	Not specified	COMPLETED	Dumping Syndrome After Operation of Esophageal Atresia Type III
NCT02883725	Not specified	COMPLETED	National Register of Oesophageal Atresia
NCT03023865	Not specified	UNKNOWN	Individualized Management for Long Gap Esophageal Atresia
NCT03415893	Not specified	COMPLETED	High-resolution Esophageal Manometry
NCT03455881	Not specified	UNKNOWN	Phenotypic and Genetic Assessment of Tracheal and Esophageal Birth Defects in Patients
NCT03615495	Not specified	COMPLETED	Flourish™ Pediatric Esophageal Atresia
NCT03619408	Not specified	UNKNOWN	Management of Esophagitis Following Repair of Esophageal Atresia
NCT03666767	Not specified	COMPLETED	Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries
NCT03730454	Not specified	ACTIVE_NOT_RECRUITING	Transanastomotic Tube for Proximal Esophageal Atresia With Distal Tracheoesophageal Fistula Repair
NCT03767673	Not specified	UNKNOWN	Cardiorespiratory Performance and Pulmonary Microbiome in Patients After Repair of Esophageal Atresia
NCT03999008	Not specified	UNKNOWN	Oral Viscous Budesonide in Anastomotic Stricture After Esophageal Atresia Repair (OVB in EA)
NCT04072419	Not specified	UNKNOWN	Application of Enhanced Recovery After Surgery for Congenital Esophageal Atresia During Perioperative Period
NCT04136795	Not specified	UNKNOWN	Evaluation of the Respiratory Impact After Conventional or Minimally Invasive Esophageal Atresia Surgery
NCT04259528	Not specified	UNKNOWN	Endoscopic Ultrasound Findings in Esophageal Atresia Following Surgical Repair
NCT04522193	Not specified	RECRUITING	Dumping Syndrome and Esophageal Atresia
NCT04901546	Not specified	COMPLETED	Esophageal Atresia: a Natural Experiment of the Effects of Oral Inoculation on the Gut Microbiome
NCT04932746	Not specified	COMPLETED	The Effect of Dexmedetomidine on Oxygen During One Lung Ventilation in Pediatric Surgery.
NCT05129930	Not specified	COMPLETED	Fluid Overload and Pulmonary Function
NCT05527873	Not specified	COMPLETED	Respiratory Complications of Operated Esophageal Atresia in Children
NCT05995171	Not specified	RECRUITING	Long Term Outcome of Easophageal Atresia : Transmics Profiles in Adolescence
NCT06073158	Not specified	COMPLETED	Molecular Signatures of Esophageal Atresia
NCT06208449	Not specified	UNKNOWN	Robotic Versus Thoracoscopy Versus Thoracotomy Repair for Congenital Esophageal Atresia
NCT06335862	Not specified	ENROLLING_BY_INVITATION	Primary Posterior Tracheopexy Prevents Tracheal Collapse
NCT06731855	Not specified	RECRUITING	An Exploratory Physiological Study of Post-operative Recovery in Surgical Neonates and Dimethylarginine:Arginine Levels
NCT06860919	Not specified	RECRUITING	Prospective Evaluation of the Results of Multidisciplinary Follow-up After a Transitional Consultation for Esophageal Atresia
NCT06975982	Not specified	RECRUITING	Symptoms, Pulmonary Function, Muscle Strength, Exercise Capacity, and Frailty in Esophageal Atresia vs. Healthy Peers
NCT07100379	Not specified	RECRUITING	Balloon Inflation Time for Esophageal Strictures (BITES): A Randomized Multi-Center Study
NCT07210736	Not specified	NOT_YET_RECRUITING	Brazilian Multicenter Study on Esophageal Atresia
NCT03223480	PHASE2/PHASE3	COMPLETED	EUS - Guided Balloon-occluded Gastrojejunostomy Bypass
NCT01139853	EARLY_PHASE1	COMPLETED	Post-Operative Impact of Nasogastric Tubes on Rates of Emesis in Infants Diagnosed With Pyloric Stenosis
NCT00144924	Not specified	TERMINATED	Open vs Laparoscopic Pyloromyotomy for Pyloric Stenosis
NCT00409734	Not specified	COMPLETED	Frequency of Formula Change Prior to the Accurate Diagnosis of Pyloric Stenosis
NCT00487552	Not specified	TERMINATED	Magnetic Anastomosis Device Relief of Malignant Gastric Outlet Obstruction
NCT00991614	Not specified	COMPLETED	EVOLUTION® Duodenal Stent for Duodenal or Gastric Outlet Obstruction Caused by Malignant Neoplasms
NCT01839292	Not specified	COMPLETED	ComVi and D-type Stent in Malignant GOO