SPIRE1

Summary

SPIRE1 (spire type actin nucleation factor 1, HGNC:30622) is a protein-coding gene on chromosome 18p11.21, encoding Protein spire homolog 1 (Q08AE8). Acts as an actin nucleation factor, remains associated with the slow-growing pointed end of the new filament.

Spire proteins, such as SPIRE1, are highly conserved between species. They belong to the family of Wiskott-Aldrich homology region-2 (WH2) proteins, which are involved in actin organization (Kerkhoff et al., 2001 [PubMed 11747823]).

Source: NCBI Gene 56907 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 97 total
• MANE Select transcript: NM_001128626

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30622
Approved symbol	SPIRE1
Name	spire type actin nucleation factor 1
Location	18p11.21
Locus type	gene with protein product
Status	Approved
Aliases	spir-1, KIAA1135
Ensembl gene	ENSG00000134278
Ensembl biotype	protein_coding
OMIM	609216
Entrez	56907

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 15 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000309836, ENST00000409402, ENST00000410092, ENST00000440472, ENST00000449797, ENST00000453447, ENST00000462226, ENST00000464481, ENST00000487491, ENST00000497844, ENST00000498803, ENST00000588236, ENST00000592156, ENST00000926391, ENST00000926392, ENST00000926393, ENST00000948124, ENST00000948125, ENST00000948126, ENST00000948127, ENST00000948128

RefSeq mRNA: 5 — MANE Select: NM_001128626 NM_001128626, NM_001128627, NM_001394323, NM_001394324, NM_020148

CCDS: CCDS32790, CCDS45829, CCDS45830, CCDS92438

Canonical transcript exons

ENST00000409402 — 17 exons

Exon	Start	End
ENSE00001183773	12493072	12493201
ENSE00001183805	12446512	12449896
ENSE00001585581	12485959	12486000
ENSE00001868861	12657530	12658107
ENSE00002957780	12535476	12535601
ENSE00003461769	12635062	12635096
ENSE00003464612	12479699	12479871
ENSE00003475618	12512454	12512531
ENSE00003507382	12546674	12546904
ENSE00003523361	12452255	12452391
ENSE00003538132	12452485	12452512
ENSE00003556375	12454346	12454483
ENSE00003573629	12463351	12463493
ENSE00003575759	12496016	12496102
ENSE00003600503	12506477	12506641
ENSE00003652430	12464868	12464958
ENSE00003691000	12453068	12453138

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 97.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.8022 / max 235.7605, expressed in 1761 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171244	15.6055	1750
171242	3.4718	1386
171243	1.3861	841
171237	0.1631	48
171241	0.1574	58
171239	0.0104	3
171240	0.0080	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	97.63	gold quality
medial globus pallidus	UBERON:0002477	97.60	gold quality
endothelial cell	CL:0000115	97.49	gold quality
epithelial cell of pancreas	CL:0000083	97.23	gold quality
ventricular zone	UBERON:0003053	97.22	gold quality
left ventricle myocardium	UBERON:0006566	97.09	gold quality
calcaneal tendon	UBERON:0003701	97.08	gold quality
cortical plate	UBERON:0005343	96.95	gold quality
globus pallidus	UBERON:0001875	96.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.46	gold quality
postcentral gyrus	UBERON:0002581	96.15	gold quality
tendon	UBERON:0000043	96.02	gold quality
pancreatic ductal cell	CL:0002079	95.94	silver quality
corpus callosum	UBERON:0002336	95.75	gold quality
parietal lobe	UBERON:0001872	95.73	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.60	gold quality
middle temporal gyrus	UBERON:0002771	95.53	gold quality
myocardium	UBERON:0002349	95.50	gold quality
superior frontal gyrus	UBERON:0002661	95.43	gold quality
sural nerve	UBERON:0015488	95.37	gold quality
entorhinal cortex	UBERON:0002728	95.25	gold quality
upper arm skin	UBERON:0004263	95.17	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.67	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.40	gold quality
secondary oocyte	CL:0000655	94.34	gold quality
tendon of biceps brachii	UBERON:0008188	94.23	gold quality
substantia nigra pars compacta	UBERON:0001965	94.17	gold quality
tibialis anterior	UBERON:0001385	94.12	gold quality
deltoid	UBERON:0001476	93.90	gold quality
occipital lobe	UBERON:0002021	93.48	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	37.14
E-ANND-3	yes	8.28
E-CURD-10	no	411.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

205 targeting SPIRE1, 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-4262	100.00	73.26	3931
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834

Literature-anchored findings (GeneRIF, showing 12)

• The multifunctional character of the WH2 domains allows Spire to sequester four G-actin subunits binding cooperatively in a tight SA(4) complex and to nucleate, sever, and cap filaments at their barbed ends. (PMID:18042452)
• both mammalian Spir proteins, Spir-1 and Spir-2, interact with mammalian Fmn subgroup proteins formin-1 and formin-2 (PMID:19605360)
• analysis of the molecular basis of the Spir1/formin-2 interaction (PMID:21705804)
• Spire-1 is specifically recruited at invadosomes and is part of a multi-molecular complex containing Src kinase, the formin mDia1 and actin. (PMID:24213528)
• Spire recruits Fmn2 and facilitates its association with actin filaments barbed ends. (PMID:24586110)
• This DNA damage-induced nuclear actin assembly requires two biologically and physically linked nucleation factors: Formin-2 and Spire-1/Spire-2. (PMID:26287480)
• The authors propose Spire1C isoform cooperates with INF2 to regulate actin assembly at endoplasmic reticulum-mitochondrial contacts. (PMID:26305500)
• Data suggest formin homology domain (FH2) of Fmn2 binds actin at filament barbed end as weak capper and plays a role in displacing WASP homology domain 2 (WH2) domains of Spire-1 from actin; competitive binding of Fmn2 vs Spire-1 aids actin assembly. (PMID:26668326)
• interferes with bacterial binding in Salmonella typhimurium host cell invasion (PMID:27627128)
• Lnc-SMaRT Translational Regulation of Spire1, A New Player in Muscle Differentiation. (PMID:34863993)
• Spire1 and Myosin Vc promote Ca(2+)-evoked externalization of von Willebrand factor in endothelial cells. (PMID:35084586)
• Nuclear F-actin assembly on damaged chromatin is regulated by DYRK1A and Spir1 phosphorylation. (PMID:38966995)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	spire1a	ENSDARG00000035868
danio_rerio	spire1b	ENSDARG00000038445
mus_musculus	Spire1	ENSMUSG00000024533
rattus_norvegicus	Spire1	ENSRNOG00000025324
drosophila_melanogaster	spir	FBGN0003475

Paralogs (1): SPIRE2 (ENSG00000204991)

Protein

Protein identifiers

Protein spire homolog 1 — Q08AE8 (reviewed: Q08AE8)

All UniProt accessions (6): C9JYR7, Q08AE8, J3KNG6, K7EMJ7, K7ENV1, K7EQR2

UniProt curated annotations — full annotation on UniProt →

Function. Acts as an actin nucleation factor, remains associated with the slow-growing pointed end of the new filament. Involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport. Required for asymmetric spindle positioning and asymmetric cell division during meiosis. Required for normal formation of the cleavage furrow and for polar body extrusion during female germ cell meiosis. Also acts in the nucleus: together with FMN2, promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage. In addition, promotes innate immune signaling downstream of dsRNA sensing. Mechanistically, contributes to IRF3 phosphorylation and activation downstream of MAVS and upstream of TBK1.

Subunit / interactions. Interacts with FMN2. (Microbial infection) Interacts (via C-terminus) with vaccinia virus protein K7/OPG41; this interaction prevents innate immune signaling activation.

Subcellular location. Cytoplasm. Cytoskeleton. Perinuclear region. Cell membrane. Cytoplasmic vesicle membrane.

Domain organisation. Binds to actin monomers via the WH2 domain. The Spir-box targets binding to intracellular membrane structures.

Similarity. Belongs to the spire family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q08AE8-1	1	yes
Q08AE8-5	5
Q08AE8-2	2
Q08AE8-3	3
Q08AE8-4	4

RefSeq proteins (5): NP_001122098, NP_001122099, NP_001381252, NP_001381253, NP_064533 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR011019	KIND_dom	Domain
IPR029901	Spire	Family
IPR029905	Spir-1_FYVE-rel_dom	Domain

Pfam: PF16474

UniProt features (48 total): modified residue 10, helix 8, strand 6, compositionally biased region 4, splice variant 4, mutagenesis site 4, region of interest 4, domain 3, initiator methionine 1, chain 1, sequence variant 1, turn 1, coiled-coil region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2YLE	X-RAY DIFFRACTION	1.8
2YLF	X-RAY DIFFRACTION	2.05
3R7G	X-RAY DIFFRACTION	2.2
3RBW	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08AE8-F1	64.78	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 (10): 2, 387, 406, 464, 465, 467, 509, 678, 682, 735

Mutagenesis-validated functional residues (4):

Position	Phenotype
131	strongly reduces interaction with fmn2.
134	abolishes interaction with fmn2.
138	abolishes interaction with fmn2.
146	abolishes interaction with fmn2.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 229 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GCM_MAP4K4, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_MITOCHONDRIAL_FISSION, GCM_PTPRD, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_SPINDLE_LOCALIZATION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, KEGG_DORSO_VENTRAL_AXIS_FORMATION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_CYTOKINETIC_PROCESS, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP

GO Biological Process (16): protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), actin cytoskeleton organization (GO:0030036), cleavage furrow formation (GO:0036089), polar body extrusion after meiotic divisions (GO:0040038), actin nucleation (GO:0045010), innate immune response (GO:0045087), intracellular transport (GO:0046907), Golgi vesicle transport (GO:0048193), establishment of meiotic spindle localization (GO:0051295), actin filament network formation (GO:0051639), formin-nucleated actin cable assembly (GO:0070649), positive regulation of mitochondrial fission (GO:0090141), positive regulation of double-strand break repair (GO:2000781), immune system process (GO:0002376), actin filament organization (GO:0007015)

GO Molecular Function (3): actin binding (GO:0003779), microtubule binding (GO:0008017), protein binding (GO:0005515)

GO Cellular Component (12): nucleoplasm (GO:0005654), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cell cortex (GO:0005938), cytoplasmic vesicle membrane (GO:0030659), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), cleavage furrow (GO:0032154)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	4
transport	3
actin filament organization	2
intracellular anatomical structure	2
cell periphery	2
intracellular protein localization	1
establishment of protein localization	1
cellular process	1
cytoskeleton organization	1
actin filament-based process	1
cytokinetic process	1
cytoskeleton-dependent cytokinesis	1
plasma membrane invagination	1
female meiotic nuclear division	1
meiotic cytokinesis	1
immune response	1
defense response to symbiont	1
cellular localization	1
establishment of localization in cell	1
vesicle-mediated transport	1
establishment of spindle localization	1
meiotic cell cycle	1
meiotic cell cycle process	1
parallel actin filament bundle assembly	1
formin-nucleated actin cable organization	1
mitochondrial fission	1
positive regulation of organelle organization	1
positive regulation of developmental process	1
regulation of mitochondrial fission	1
double-strand break repair	1
positive regulation of DNA repair	1
regulation of double-strand break repair	1
biological_process	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
cytoskeletal protein binding	1
tubulin binding	1
binding	1
nuclear lumen	1

Protein interactions and networks

STRING

1481 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPIRE1	FMN1	Q68DA7	953
SPIRE1	FMN2	Q9NZ56	925
SPIRE1	INF2	Q27J81	675
SPIRE1	WAS	P42768	646
SPIRE1	PCSK9	Q8NBP7	626
SPIRE1	RAB3A	P20336	594
SPIRE1	FHOD1	Q9Y613	573
SPIRE1	ANXA2	P07355	573
SPIRE1	JMY	Q8N9B5	548
SPIRE1	RAB11A	P24410	513
SPIRE1	PFN4	Q8NHR9	474
SPIRE1	LMOD2	Q6P5Q4	470
SPIRE1	MT-CO1	P00395	459
SPIRE1	LMOD3	Q0VAK6	459
SPIRE1	MYO5B	Q9ULV0	455

IntAct

46 interactions, top by confidence:

A	B	Type	Score
OPG044	DDX3X	psi-mi:“MI:0914”(association)	0.730
BCL7A	ARID1A	psi-mi:“MI:0914”(association)	0.640
BCL7C	ARID1A	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
SPIRE1	BBS4	psi-mi:“MI:0915”(physical association)	0.560
SPIRE1	ATP1A3	psi-mi:“MI:0915”(physical association)	0.560
SPIRE1	PECAM1	psi-mi:“MI:0915”(physical association)	0.560
PLD1	SPIRE1	psi-mi:“MI:0915”(physical association)	0.560
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
SPIRE1	NPHP4	psi-mi:“MI:0915”(physical association)	0.400
SPIRE1	SFN	psi-mi:“MI:0915”(physical association)	0.400
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
YWHAZ	SPEG	psi-mi:“MI:0914”(association)	0.350
YWHAH	SHTN1	psi-mi:“MI:0914”(association)	0.350
ACTB	ENAH	psi-mi:“MI:0914”(association)	0.350
ACTG1	ENAH	psi-mi:“MI:0914”(association)	0.350

BioGRID (41): SPIRE1 (Affinity Capture-MS), SPIRE1 (Affinity Capture-MS), SPIRE1 (Affinity Capture-MS), SPIRE1 (Affinity Capture-MS), SPIRE1 (Affinity Capture-MS), SPIRE1 (Affinity Capture-RNA), SPIRE1 (Affinity Capture-RNA), SPIRE1 (Affinity Capture-MS), SPIRE1 (Affinity Capture-MS), SPIRE1 (Affinity Capture-MS), SPIRE1 (Affinity Capture-MS), BBS4 (Two-hybrid), SPIRE1 (Affinity Capture-MS), SPIRE1 (Affinity Capture-MS), SPIRE1 (Affinity Capture-MS)

ESM2 similar proteins: A0A571BF63, A0A8M9QN10, A1L1K1, A2AVJ5, E7FEV0, O00443, O08576, O43147, P0C6P5, P59438, P59729, P97433, Q08AE8, Q12923, Q13009, Q1LYM3, Q2NKQ1, Q5EB20, Q5PQS0, Q5RAY1, Q5RD34, Q5SXA9, Q5U3W3, Q5U464, Q5VUB5, Q60610, Q61194, Q64512, Q6MZQ0, Q6NXJ0, Q6ZUJ8, Q7TNN8, Q7TSI1, Q7Z3E5, Q803Q4, Q80U12, Q8BPQ7, Q8N1W1, Q8N957, Q8ND30

Diamond homologs: Q08AE8, Q1LYM3, Q4R707, Q52KF3, Q5U3H9, Q8K1S6, Q8WWL2, Q29KT5, Q9U1K1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 41 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	7	156.8×	7e-13
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	138.3×	1e-12
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	138.3×	1e-12
Activation of BH3-only proteins	7	102.2×	1e-11
RHO GTPases activate PKNs	7	65.3×	3e-10
Intrinsic Pathway for Apoptosis	7	60.3×	4e-10
FOXO-mediated transcription	5	49.4×	5e-07
Translocation of SLC2A4 (GLUT4) to the plasma membrane	10	45.4×	7e-13

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	48.2×	1e-05
intracellular protein localization	8	22.0×	1e-06
chromatin remodeling	6	11.5×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3654 predictions. Top by Δscore:

Variant	Effect	Δscore
18:12449892:AGAAC:A	acceptor_gain	1.0000
18:12449893:GAAC:G	acceptor_gain	1.0000
18:12449894:AAC:A	acceptor_gain	1.0000
18:12449895:AC:A	acceptor_gain	1.0000
18:12449896:CC:C	acceptor_gain	1.0000
18:12449896:CCTGG:C	acceptor_loss	1.0000
18:12449897:C:CC	acceptor_gain	1.0000
18:12449902:G:C	acceptor_gain	1.0000
18:12449902:G:GC	acceptor_gain	1.0000
18:12449909:C:CT	acceptor_gain	1.0000
18:12449910:A:T	acceptor_gain	1.0000
18:12454349:T:TA	donor_gain	1.0000
18:12454479:TCCTC:T	acceptor_gain	1.0000
18:12454480:CCTCC:C	acceptor_gain	1.0000
18:12454482:TCC:T	acceptor_loss	1.0000
18:12454485:T:C	acceptor_loss	1.0000
18:12463349:A:AC	donor_gain	1.0000
18:12463350:C:CC	donor_gain	1.0000
18:12463492:CT:C	acceptor_gain	1.0000
18:12463494:C:CC	acceptor_gain	1.0000
18:12464866:A:AC	donor_gain	1.0000
18:12464867:C:CC	donor_gain	1.0000
18:12464867:CT:C	donor_gain	1.0000
18:12479693:CCTCA:C	donor_loss	1.0000
18:12479694:CTCA:C	donor_loss	1.0000
18:12479695:TCAC:T	donor_loss	1.0000
18:12479696:CACCT:C	donor_loss	1.0000
18:12479698:CCTCA:C	donor_loss	1.0000
18:12493067:CTCA:C	donor_loss	1.0000
18:12493068:TCACC:T	donor_loss	1.0000

AlphaMissense

4914 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:12449794:G:C	C705W	1.000
18:12449795:C:A	C705F	1.000
18:12449795:C:T	C705Y	1.000
18:12449796:A:G	C705R	1.000
18:12449803:A:C	C702W	1.000
18:12449804:C:T	C702Y	1.000
18:12449805:A:G	C702R	1.000
18:12452496:A:G	C622R	1.000
18:12452503:G:C	C619W	1.000
18:12452505:A:G	C619R	1.000
18:12453073:A:C	C614W	1.000
18:12453074:C:T	C614Y	1.000
18:12453075:A:G	C614R	1.000
18:12453082:A:C	C611W	1.000
18:12453083:C:T	C611Y	1.000
18:12453084:A:G	C611R	1.000
18:12453126:A:G	C597R	1.000
18:12453133:G:C	C594W	1.000
18:12453134:C:G	C594S	1.000
18:12453134:C:T	C594Y	1.000
18:12453135:A:G	C594R	1.000
18:12453135:A:T	C594S	1.000
18:12454405:C:G	A573P	1.000
18:12454413:A:G	L570P	1.000
18:12454416:A:T	V569D	1.000
18:12454422:C:G	R567P	1.000
18:12454423:G:T	R567S	1.000
18:12454425:A:T	I566N	1.000
18:12454449:A:T	L558H	1.000
18:12496041:A:C	I345S	1.000

dbSNP variants (sampled 300 via entrez): RS1000017687 (18:12556019 T>C), RS1000018450 (18:12659565 G>A,T), RS1000021839 (18:12599307 G>A,C), RS1000023160 (18:12541175 C>A), RS1000035195 (18:12581156 G>A), RS1000062530 (18:12641060 A>C), RS1000062690 (18:12617918 G>A), RS1000069008 (18:12472794 G>C), RS1000076736 (18:12631663 C>G), RS1000085653 (18:12466672 C>A), RS1000093388 (18:12447559 C>T), RS1000100877 (18:12599711 C>T), RS1000113143 (18:12663052 A>G), RS1000123520 (18:12557738 C>T), RS1000123798 (18:12490959 A>G)

Disease associations

OMIM: gene MIM:609216 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001491_27	Immune response to smallpox vaccine (IL-6)	3.000000e-08
GCST001491_33	Immune response to smallpox vaccine (IL-6)	8.000000e-07
GCST004162_8	Carotid plaque burden	8.000000e-06
GCST90002383_83	Hematocrit	2.000000e-10
GCST90002384_430	Hemoglobin	5.000000e-09
GCST90002403_328	Red blood cell count	4.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0006501	carotid plaque build
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	9
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Cyclosporine	increases expression	3
Arsenic	increases abundance, increases expression, decreases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Tobacco Smoke Pollution	increases expression, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
manganese chloride	decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
14-deoxy-11,12-didehydroandrographolide	increases expression	1
abrine	increases expression	1
dorsomorphin	decreases expression, increases expression, affects cotreatment	1
PCI 5002	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TQ19	HAP1 SPIRE1 (-) 1	Cancer cell line	Male
CVCL_TQ20	HAP1 SPIRE1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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