SIPA1L1

Summary

SIPA1L1 (signal induced proliferation associated 1 like 1, HGNC:20284) is a protein-coding gene on chromosome 14q24.2, encoding Signal-induced proliferation-associated 1-like protein 1 (O43166). Stimulates the GTPase activity of RAP2A.

Predicted to enable GTPase activator activity; actin filament binding activity; and protein kinase binding activity. Predicted to be involved in several processes, including activation of GTPase activity; ephrin receptor signaling pathway; and regulation of postsynapse organization. Located in actin cytoskeleton and plasma membrane.

Source: NCBI Gene 26037 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 276 total
• MANE Select transcript: NM_001386936

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20284
Approved symbol	SIPA1L1
Name	signal induced proliferation associated 1 like 1
Location	14q24.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0440, E6TP1, SPAR1
Ensembl gene	ENSG00000197555
Ensembl biotype	protein_coding
OMIM	617504
Entrez	26037

Gene structure

Transcript identifiers

Ensembl transcripts: 84 — 72 protein_coding, 10 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000358550, ENST00000381232, ENST00000537413, ENST00000553453, ENST00000554126, ENST00000554362, ENST00000554874, ENST00000554960, ENST00000555066, ENST00000555652, ENST00000555818, ENST00000555989, ENST00000556408, ENST00000556780, ENST00000556959, ENST00000557151, ENST00000557469, ENST00000557712, ENST00000869378, ENST00000869379, ENST00000869380, ENST00000869381, ENST00000869382, ENST00000869383, ENST00000869384, ENST00000869385, ENST00000869386, ENST00000869387, ENST00000869388, ENST00000869389, ENST00000869390, ENST00000869391, ENST00000869392, ENST00000869393, ENST00000869394, ENST00000869395, ENST00000869396, ENST00000869397, ENST00000936027, ENST00000936028, ENST00000936029, ENST00000936030, ENST00000936031, ENST00000936032, ENST00000936033, ENST00000936034, ENST00000936035, ENST00000936036, ENST00000936037, ENST00000936038, ENST00000936039, ENST00000936040, ENST00000936041, ENST00000936042, ENST00000936043, ENST00000936044, ENST00000936045, ENST00000936046, ENST00000936047, ENST00000936048, ENST00000936049, ENST00000936050, ENST00000936051, ENST00000936052, ENST00000936053, ENST00000936054, ENST00000936055, ENST00000936056, ENST00000936057, ENST00000936058, ENST00000936059, ENST00000936060, ENST00000936061, ENST00000936062, ENST00000936063, ENST00000936064, ENST00000962882, ENST00000962883, ENST00000962884, ENST00000962885, ENST00000962886, ENST00000962887, ENST00000962888, ENST00000962889

RefSeq mRNA: 10 — MANE Select: NM_001386936 NM_001284245, NM_001284246, NM_001284247, NM_001354285, NM_001354286, NM_001354287, NM_001354288, NM_001354289, NM_001386936, NM_015556

CCDS: CCDS61490, CCDS61491, CCDS9807

Canonical transcript exons

ENST00000381232 — 24 exons

Exon	Start	End
ENSE00000911782	71624048	71624236
ENSE00000911784	71650335	71650509
ENSE00000911790	71671119	71671692
ENSE00000911792	71672348	71672622
ENSE00000911796	71698981	71699127
ENSE00001097265	71658333	71658436
ENSE00001369903	71587571	71589370
ENSE00001760225	71661310	71661467
ENSE00002449640	71512743	71512845
ENSE00002468135	71529312	71529370
ENSE00002494771	71320476	71320503
ENSE00002501168	71739018	71741209
ENSE00002503407	71321122	71321181
ENSE00003469647	71730055	71730301
ENSE00003497531	71709222	71709664
ENSE00003509198	71724670	71724835
ENSE00003531385	71738241	71738325
ENSE00003537412	71705222	71705340
ENSE00003561678	71702381	71702505
ENSE00003577333	71735277	71735391
ENSE00003609754	71723647	71723886
ENSE00003652883	71618757	71618887
ENSE00003672241	71733666	71733812
ENSE00003687637	71685362	71685631

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 94.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.3517 / max 1541.1556, expressed in 1807 samples.

FANTOM5 promoters (28 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140436	21.9619	1793
140443	6.6194	1496
140444	2.8521	844
140442	2.6466	1073
140438	1.1963	670
140437	0.6899	326
140462	0.6475	198
140457	0.3391	72
140468	0.2827	117
140465	0.2463	123

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	94.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.56	gold quality
lateral globus pallidus	UBERON:0002476	94.54	gold quality
caudate nucleus	UBERON:0001873	94.19	gold quality
CA1 field of hippocampus	UBERON:0003881	94.13	gold quality
right frontal lobe	UBERON:0002810	94.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.01	gold quality
sural nerve	UBERON:0015488	93.79	gold quality
cerebellar cortex	UBERON:0002129	93.72	gold quality
cerebellar hemisphere	UBERON:0002245	93.70	gold quality
adrenal tissue	UBERON:0018303	93.64	gold quality
popliteal artery	UBERON:0002250	93.59	gold quality
tibial artery	UBERON:0007610	93.59	gold quality
cerebellum	UBERON:0002037	93.38	gold quality
primary visual cortex	UBERON:0002436	93.24	gold quality
putamen	UBERON:0001874	93.22	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.14	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.10	gold quality
Brodmann (1909) area 10	UBERON:0013541	92.96	gold quality
frontal cortex	UBERON:0001870	92.93	gold quality
adenohypophysis	UBERON:0002196	92.93	gold quality
occipital lobe	UBERON:0002021	92.87	gold quality
spleen	UBERON:0002106	92.85	gold quality
cingulate cortex	UBERON:0003027	92.85	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.84	gold quality
anterior cingulate cortex	UBERON:0009835	92.79	gold quality
neocortex	UBERON:0001950	92.76	gold quality
telencephalon	UBERON:0001893	92.74	gold quality
entorhinal cortex	UBERON:0002728	92.74	gold quality
right adrenal gland cortex	UBERON:0035827	92.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.08
E-MTAB-9801	yes	6.14
E-CURD-119	yes	5.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting SIPA1L1, 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-4283	100.00	66.42	2097
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4698	99.84	71.41	4303

Literature-anchored findings (GeneRIF, showing 3)

• investigated the consequences of human papillomavirus 31 E6 binding to E6TP1; observed that binding & degradation of E6TP1 by HPV type 31 E6 are required to extend life span of keratinocytes & the long-term, stable replication of the viral genome (PMID:16999984)
• Sipa1L1 is conserved across species, has a distinct expression pattern in brain and is localized to excitatory postsynapses. (PMID:26364583)
• Hunting for Familial Parkinson’s Disease Mutations in the Post Genome Era. (PMID:33802862)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sipa1l1	ENSDARG00000020134
mus_musculus	Sipa1l1	ENSMUSG00000042700
rattus_norvegicus	Sipa1l1	ENSRNOG00000007646
drosophila_melanogaster	RapGAP1	FBGN0264895
caenorhabditis_elegans		WBGENE00018734

Paralogs (6): RAP1GAP (ENSG00000076864), SIPA1L3 (ENSG00000105738), SIPA1L2 (ENSG00000116991), RAP1GAP2 (ENSG00000132359), GARNL3 (ENSG00000136895), SIPA1 (ENSG00000213445)

Protein

Protein identifiers

Signal-induced proliferation-associated 1-like protein 1 — O43166 (reviewed: O43166)

Alternative names: High-risk human papilloma viruses E6 oncoproteins targeted protein 1

All UniProt accessions (4): O43166, F5GYF8, G3V4Z3, H0YJY2

UniProt curated annotations — full annotation on UniProt →

Function. Stimulates the GTPase activity of RAP2A. Promotes reorganization of the actin cytoskeleton and recruits DLG4 to F-actin. Contributes to the regulation of dendritic spine morphogenesis.

Subunit / interactions. Interacts with DLG4, PDLIM5, PDLIM7 and LZTS3. Interacts with the actin cytoskeleton. Interacts (via PDZ domain) with EPHA4 (via PDZ motif); controls neuronal morphology through regulation of the RAP1 (RAP1A or RAP1B) and RAP2 (RAP2A, RAP2B or RAP2C) GTPases. Interacts with HPV E6.

Subcellular location. Cytoplasm. Cytoskeleton. Postsynaptic density. Synapse. Synaptosome.

Tissue specificity. Widely expressed.

Post-translational modifications. Ubiquitinated and degraded by the SCF(BTRC) following phosphorylation by PLK2. Phosphorylated at Ser-1349 by CDK5, creating a docking site for the POLO box domains of PLK2. Subsequently, PLK2 binds and phosphorylates SIPA1L1, leading to ubiquitination and degradation by the proteasome.

Isoforms (3)

UniProt ID	Names	Canonical?
O43166-1	1, E6TP1 beta	yes
O43166-2	2, E6TP1 alpha
O43166-3	3

RefSeq proteins (10): NP_001271174, NP_001271175, NP_001271176, NP_001341214, NP_001341215, NP_001341216, NP_001341217, NP_001341218, NP_001373865, NP_056371 (=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 (75 total): modified residue 42, compositionally biased region 13, region of interest 9, sequence conflict 3, domain 2, splice variant 2, sequence variant 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43166-F1	55.15	0.19

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 (42): 162, 187, 193, 208, 255, 288, 1078, 1087, 1116, 1127, 1149, 1170, 1181, 1255, 1270, 1326, 1330, 1349, 1366, 1390 …

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6794361	Neurexins and neuroligins
R-HSA-112316	Neuronal System
R-HSA-6794362	Protein-protein interactions at synapses

MSigDB gene sets: 294 (showing top): GOBP_DENDRITE_DEVELOPMENT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_ACTIVATION_OF_GTPASE_ACTIVITY, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEUROGENESIS, MEF2_02, GOBP_CELL_CELL_SIGNALING, IRF7_01, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY

GO Biological Process (8): actin cytoskeleton organization (GO:0030036), regulation of GTPase activity (GO:0043087), ephrin receptor signaling pathway (GO:0048013), regulation of synaptic plasticity (GO:0048167), regulation of axonogenesis (GO:0050770), regulation of small GTPase mediated signal transduction (GO:0051056), regulation of dendritic spine morphogenesis (GO:0061001), activation of GTPase activity (GO:0090630)

GO Molecular Function (3): GTPase activator activity (GO:0005096), ephrin receptor binding (GO:0046875), protein binding (GO:0005515)

GO Cellular Component (8): cytoplasm (GO:0005737), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), actin cytoskeleton (GO:0015629), dendritic spine (GO:0043197), cytoskeleton (GO:0005856), neuron projection (GO:0043005), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein-protein interactions at synapses	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase activity	2
regulation of neuron projection development	2
regulation of anatomical structure morphogenesis	2
cytoskeleton organization	1
actin filament-based process	1
regulation of hydrolase activity	1
cell surface receptor protein tyrosine kinase signaling pathway	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
axonogenesis	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
dendritic spine morphogenesis	1
regulation of postsynapse organization	1
positive regulation of GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
signaling receptor binding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
membrane	1
cell periphery	1
asymmetric synapse	1
postsynaptic specialization	1
cytoskeleton	1
dendrite	1
neuron spine	1
postsynapse	1
intracellular membraneless organelle	1
plasma membrane bounded cell projection	1
cell junction	1

Protein interactions and networks

STRING

990 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIPA1L1	LZTS3	O60299	911
SIPA1L1	SHANK3	Q9BYB0	807
SIPA1L1	LZTS1	Q9Y250	787
SIPA1L1	LZTS2	Q9BRK4	716
SIPA1L1	UBE3A	P78355	651
SIPA1L1	TADA3	O75528	620
SIPA1L1	DLG4	P78352	590
SIPA1L1	RCN2	Q14257	582
SIPA1L1	FHIP1A	Q05DH4	508
SIPA1L1	GULP1	Q9UBP9	480
SIPA1L1	LRPAP1	P30533	477
SIPA1L1	TP53	P04637	472
SIPA1L1	TMEM35A	Q53FP2	459
SIPA1L1	IRF3	Q14653	451
SIPA1L1	EPHA4	P54764	428

IntAct

205 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
STAMBPL1	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
SIPA1L1	E6	psi-mi:“MI:0915”(physical association)	0.620
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
SIPA1L1	DLG4	psi-mi:“MI:0915”(physical association)	0.590
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
FKBP6	EEF2K	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
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
PIP	TBKBP1	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	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
ABCC4	SIPA1L1	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF16	SIPA1L1	psi-mi:“MI:0407”(direct interaction)	0.440
ASIC3	SIPA1L1	psi-mi:“MI:0407”(direct interaction)	0.440
ATP2B4	SIPA1L1	psi-mi:“MI:0407”(direct interaction)	0.440
CYSLTR2	SIPA1L1	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	SIPA1L1	psi-mi:“MI:0407”(direct interaction)	0.440
DGKZ	SIPA1L1	psi-mi:“MI:0407”(direct interaction)	0.440
DOCK4	SIPA1L1	psi-mi:“MI:0407”(direct interaction)	0.440
FRMPD4	SIPA1L1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (219): SIPA1L1 (Affinity Capture-MS), SIPA1L1 (Affinity Capture-MS), SIPA1L1 (Affinity Capture-MS), SIPA1L1 (Affinity Capture-MS), SIPA1L1 (Proximity Label-MS), SIPA1L1 (Proximity Label-MS), SIPA1L1 (Proximity Label-MS), SIPA1L1 (Proximity Label-MS), SIPA1L1 (Proximity Label-MS), SIPA1L1 (Proximity Label-MS), SIPA1L1 (Affinity Capture-MS), SIPA1L1 (Affinity Capture-MS), SIPA1L1 (Affinity Capture-MS), SIPA1L1 (Affinity Capture-MS), SIPA1L1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IVA4, A1Z7A6, A4D256, A6N3Q4, A8XQD5, B3M301, B3P8A3, B4G437, B4HGG6, B4JII0, B4K799, B4M0H8, B4NBP4, B4PL32, B4QSF0, B7WN72, G5EFD2, O02626, O43078, O43166, O60729, P24583, P34400, P34680, P43125, P50527, P81299, Q00684, Q07292, Q19469, Q19857, Q298L4, Q59NH8, Q5B323, Q61UC4, Q6GQT0, Q6NRL1, Q6PFY9, Q8BXK8, Q8I0P1

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

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
UBE3A	“down-regulates quantity by destabilization”	SIPA1L1	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 197 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	43.7×	6e-10
Activation of BAD and translocation to mitochondria	7	43.3×	1e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	38.2×	2e-08
Activation of BH3-only proteins	7	28.3×	2e-07
RHO GTPases activate PKNs	8	20.6×	2e-07
Signaling by RAS mutants	6	20.6×	1e-05
Intrinsic Pathway for Apoptosis	7	16.7×	7e-06
MAP2K and MAPK activation	7	16.2×	8e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	7	14.4×	3e-04
negative regulation of translation	7	7.7×	8e-03
intracellular protein localization	13	7.6×	2e-05
regulation of small GTPase mediated signal transduction	9	7.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	221
Likely benign	14
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

4814 predictions. Top by Δscore:

Variant	Effect	Δscore
14:71577278:G:GT	donor_gain	1.0000
14:71618750:A:AG	acceptor_gain	1.0000
14:71618752:CTAAG:C	acceptor_loss	1.0000
14:71618753:TAA:T	acceptor_loss	1.0000
14:71618754:A:AG	acceptor_gain	1.0000
14:71618754:AAGAA:A	acceptor_loss	1.0000
14:71618755:A:AG	acceptor_gain	1.0000
14:71618755:AGAAC:A	acceptor_loss	1.0000
14:71618756:G:GG	acceptor_gain	1.0000
14:71618756:G:T	acceptor_loss	1.0000
14:71618756:GAAC:G	acceptor_gain	1.0000
14:71618756:GAACA:G	acceptor_gain	1.0000
14:71618760:A:AG	acceptor_gain	1.0000
14:71618883:GTGAG:G	donor_gain	1.0000
14:71618885:GAGGT:G	donor_loss	1.0000
14:71618887:GGTAA:G	donor_loss	1.0000
14:71618888:G:A	donor_loss	1.0000
14:71618889:T:A	donor_loss	1.0000
14:71624042:TTGCA:T	acceptor_loss	1.0000
14:71624046:A:AG	acceptor_gain	1.0000
14:71624046:AGC:A	acceptor_loss	1.0000
14:71624047:G:GA	acceptor_gain	1.0000
14:71624047:GC:G	acceptor_gain	1.0000
14:71624047:GCT:G	acceptor_gain	1.0000
14:71624047:GCTC:G	acceptor_gain	1.0000
14:71624047:GCTCA:G	acceptor_gain	1.0000
14:71624202:TCACA:T	donor_gain	1.0000
14:71624232:AAGGG:A	donor_gain	1.0000
14:71624233:AGGG:A	donor_gain	1.0000
14:71624234:GGG:G	donor_gain	1.0000

AlphaMissense

11746 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:71588093:T:C	M74T	1.000
14:71588094:G:A	M74I	1.000
14:71588094:G:C	M74I	1.000
14:71588094:G:T	M74I	1.000
14:71588095:G:A	G75R	1.000
14:71588095:G:C	G75R	1.000
14:71588095:G:T	G75W	1.000
14:71588096:G:A	G75E	1.000
14:71588102:G:C	R77T	1.000
14:71588102:G:T	R77M	1.000
14:71588103:G:C	R77S	1.000
14:71588103:G:T	R77S	1.000
14:71588109:G:C	R79S	1.000
14:71588109:G:T	R79S	1.000
14:71588119:T:A	W83R	1.000
14:71588119:T:C	W83R	1.000
14:71588398:A:C	S176R	1.000
14:71588400:T:A	S176R	1.000
14:71588400:T:G	S176R	1.000
14:71588494:A:C	S208R	1.000
14:71588496:C:A	S208R	1.000
14:71588496:C:G	S208R	1.000
14:71588756:T:A	I295N	1.000
14:71588756:T:C	I295T	1.000
14:71588759:T:C	F296S	1.000
14:71588768:T:C	L299S	1.000
14:71588884:A:C	S338R	1.000
14:71588886:T:A	S338R	1.000
14:71588886:T:G	S338R	1.000
14:71589334:G:C	G488R	1.000

dbSNP variants (sampled 300 via entrez): RS1000008435 (14:71448418 G>A), RS1000010732 (14:71576368 A>C), RS1000025520 (14:71668478 A>G), RS1000045249 (14:71668283 A>C,G), RS1000048742 (14:71439102 A>C), RS1000052338 (14:71709080 C>T), RS1000053219 (14:71624809 G>A,T), RS1000057176 (14:71421774 G>C), RS1000062730 (14:71492730 T>TC), RS1000076020 (14:71405923 G>A), RS1000087618 (14:71361413 T>C), RS1000090421 (14:71528553 C>G), RS1000103334 (14:71661889 G>A,C,T), RS1000113087 (14:71631907 G>C), RS1000115893 (14:71471233 G>C)

Disease associations

OMIM: gene MIM:617504 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST001762_652	Obesity-related traits	1.000000e-06
GCST003094_6	Mitral valve prolapse	2.000000e-08
GCST003264_218	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST003598_34	QRS duration	2.000000e-10
GCST003598_5	QRS duration	6.000000e-13
GCST003844_44	QRS duration	4.000000e-14
GCST004733_8	Heart rate variability traits (RMSSD)	5.000000e-11
GCST004733_9	Heart rate variability traits (RMSSD)	1.000000e-11
GCST004734_8	Heart rate variability traits (SDNN)	2.000000e-14
GCST005232_138	Neuroticism	1.000000e-07
GCST006100_4	Strenuous sports or other exercises	2.000000e-09
GCST006444_1	Bone mineral density (hip)	1.000000e-10
GCST007045_42	PR interval	6.000000e-13
GCST007103_22	QRS duration	2.000000e-18
GCST007104_22	QRS duration	1.000000e-30
GCST007227_6	QRS duration	2.000000e-16
GCST007709_127	General factor of neuroticism	1.000000e-08
GCST010796_1261	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-13
GCST010796_1262	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-13
GCST010796_1263	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-13
GCST010796_1264	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-11
GCST010796_1265	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST011010_58	Electrocardiographic traits (multivariate)	5.000000e-07
GCST012114_18	Sociability score	2.000000e-08
GCST90000050_71	Age at first birth	2.000000e-08

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004713	FEV/FVC ratio
EFO:0005054	QRS complex
EFO:0008003	heart rate variability measurement
EFO:0007660	neuroticism measurement
EFO:0008002	physical activity measurement
EFO:0007702	hip bone mineral density
EFO:0004462	PR interval
EFO:0004327	electrocardiography
EFO:0009592	social interaction measurement
EFO:0009101	age at first birth measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	5
bisphenol A	increases expression, decreases expression, decreases methylation	3
sodium arsenite	affects expression, decreases expression, increases abundance, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	3
entinostat	decreases expression, affects cotreatment	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression	2
Cisplatin	affects cotreatment, decreases expression	2
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
bufotalin	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
pirinixic acid	affects binding, decreases expression, increases activity	1
arsenite	affects binding, decreases reaction	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	increases abundance, decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	decreases expression, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects 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
jinfukang	affects cotreatment, decreases expression	1
Acrolein	decreases expression, increases abundance, affects cotreatment	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1

Clinical trials (associated diseases)

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