SSH2

Summary

SSH2 (slingshot protein phosphatase 2, HGNC:30580) is a protein-coding gene on chromosome 17q11.2, encoding Protein phosphatase Slingshot homolog 2 (Q76I76). Protein phosphatase which regulates actin filament dynamics.

This gene encodes a protein tyrosine phosphatase that plays a key role in the regulation of actin filaments. The encoded protein dephosphorylates and activates cofilin, which promotes actin filament depolymerization. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 85464 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 174 total
• Druggable target: yes
• MANE Select transcript: NM_001282129

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30580
Approved symbol	SSH2
Name	slingshot protein phosphatase 2
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1725
Ensembl gene	ENSG00000141298
Ensembl biotype	protein_coding
OMIM	606779
Entrez	85464

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000269033, ENST00000324677, ENST00000394848, ENST00000540801, ENST00000577483, ENST00000577991, ENST00000578411, ENST00000579040, ENST00000579954, ENST00000582084, ENST00000590153, ENST00000592397, ENST00000649863

RefSeq mRNA: 4 — MANE Select: NM_001282129 NM_001282129, NM_001282130, NM_001282131, NM_033389

CCDS: CCDS11253, CCDS74024, CCDS92286

Canonical transcript exons

ENST00000540801 — 16 exons

Exon	Start	End
ENSE00000947602	29635968	29636802
ENSE00001290380	29625938	29632931
ENSE00001295166	29648144	29648344
ENSE00002920308	29929938	29930228
ENSE00003492672	29666867	29666995
ENSE00003498114	29684563	29684684
ENSE00003513457	29848849	29848929
ENSE00003523041	29793894	29793937
ENSE00003542573	29650654	29650800
ENSE00003545354	29702959	29703062
ENSE00003571364	29655561	29655607
ENSE00003583722	29676820	29676885
ENSE00003591212	29671935	29672129
ENSE00003646081	29667130	29667223
ENSE00003690126	29695459	29695523
ENSE00003693774	29677673	29677741

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 97.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.4397 / max 1689.8694, expressed in 1822 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165174	26.4788	1820
165169	13.0236	1196
165170	0.9532	379
165167	0.7646	325
165168	0.7529	242
165171	0.4666	193

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	97.47	gold quality
deltoid	UBERON:0001476	96.24	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.08	gold quality
blood	UBERON:0000178	95.89	gold quality
gastrocnemius	UBERON:0001388	95.88	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.88	gold quality
muscle of leg	UBERON:0001383	95.44	gold quality
skeletal muscle organ	UBERON:0014892	95.22	gold quality
skeletal muscle tissue	UBERON:0001134	94.71	gold quality
quadriceps femoris	UBERON:0001377	94.40	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.39	gold quality
muscle tissue	UBERON:0002385	93.75	gold quality
vastus lateralis	UBERON:0001379	93.74	gold quality
leukocyte	CL:0000738	93.62	gold quality
monocyte	CL:0000576	93.57	gold quality
biceps brachii	UBERON:0001507	93.53	gold quality
buccal mucosa cell	CL:0002336	93.02	gold quality
left ventricle myocardium	UBERON:0006566	93.00	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.78	gold quality
bone marrow cell	CL:0002092	92.44	gold quality
sural nerve	UBERON:0015488	92.26	gold quality
thymus	UBERON:0002370	92.22	gold quality
ileal mucosa	UBERON:0000331	92.02	gold quality
granulocyte	CL:0000094	91.17	gold quality
tendon of biceps brachii	UBERON:0008188	91.10	gold quality
myocardium	UBERON:0002349	89.95	gold quality
right lung	UBERON:0002167	89.93	gold quality
bone marrow	UBERON:0002371	89.77	gold quality
medial globus pallidus	UBERON:0002477	89.55	gold quality
calcaneal tendon	UBERON:0003701	89.43	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	39.90
E-CURD-119	yes	23.73
E-HCAD-4	yes	21.01
E-ANND-3	yes	14.21
E-ANND-2	no	1510.82

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TAL1

miRNA regulators (miRDB)

240 targeting SSH2, 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-8485	100.00	77.57	4731
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5193	100.00	67.26	1744
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-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-6758-5P	100.00	66.21	1470
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-4789-3P	99.99	70.75	2484
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 4)

• Expression of phosphatase-dead versions of SSH proteins, SSH1, SSH2 & SSH3 results in phosphorylation/inactivation of cofilin, changes in cytoskeleton organization, loss of cell polarity, and assembly of aberrant arrays of laminin-332 in keratinocytes. (PMID:17848544)
• data indicate that: (a) apoptotic cell death in FLCN-null cells can be triggered by SSH2 knockdown through cell cycle arrest; (b) SSH2 represents a potential therapeutic target for the development of agents for the treatment of BHD syndrome related tumors (PMID:23416984)
• Novel signaling pathway consisting of chemoattractant GPCR/Galphai protein, PLC, PKCbeta and PKDs that regulates SSH2/cofilin activity, F-actin polymerization and directional assembly of actin cytoskeleton in neutrophil chemotaxis was identified. (PMID:25568344)
• the N-terminal region of human Slingshot2 auto-inhibits its phosphatase activity in a noncompetitive manner (PMID:30154244)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ssh2a	ENSDARG00000088440
danio_rerio	ssh2b	ENSDARG00000098955
mus_musculus	Ssh2	ENSMUSG00000037926
rattus_norvegicus	Ssh2	ENSRNOG00000014285

Paralogs (31): DUSP13B (ENSG00000079393), DUSP12 (ENSG00000081721), SSH1 (ENSG00000084112), DUSP3 (ENSG00000108861), PTPMT1 (ENSG00000110536), DUSP16 (ENSG00000111266), EPM2A (ENSG00000112425), DUSP22 (ENSG00000112679), DUSP1 (ENSG00000120129), DUSP4 (ENSG00000120875), STYXL1 (ENSG00000127952), DUSP9 (ENSG00000130829), DUSP26 (ENSG00000133878), DUSP5 (ENSG00000138166), DUSP6 (ENSG00000139318), DUSP10 (ENSG00000143507), DUSP15 (ENSG00000149599), DUSP2 (ENSG00000158050), KASH5 (ENSG00000161609), DUSP19 (ENSG00000162999), DUSP7 (ENSG00000164086), DUSP18 (ENSG00000167065), SSH3 (ENSG00000172830), DUSP8 (ENSG00000184545), DUSP28 (ENSG00000188542), DUSP29 (ENSG00000188716), DUSP21 (ENSG00000189037), STYX (ENSG00000198252), STYXL2 (ENSG00000198842), DUSP14 (ENSG00000276023), DUSP13A (ENSG00000293543)

Protein

Protein identifiers

Protein phosphatase Slingshot homolog 2 — Q76I76 (reviewed: Q76I76)

Alternative names: SSH-like protein 2

All UniProt accessions (9): A0A3B3IS79, A0A3B3ITS1, Q76I76, F5H527, J3KSP5, J3KSQ9, K7EKN7, K7EP00, K7EQZ0

UniProt curated annotations — full annotation on UniProt →

Function. Protein phosphatase which regulates actin filament dynamics. Dephosphorylates and activates the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Inhibitory phosphorylation of cofilin is mediated by LIMK1, which may also be dephosphorylated and inactivated by this protein. Required for spermatogenesis. Involved in acrosome biogenesis, probably by regulating cofilin-mediated actin cytoskeleton remodeling during proacrosomal vesicle fusion and/or Golgi to perinuclear vesicle trafficking.

Subunit / interactions. Interacts with filamentous actin.

Subcellular location. Cytoplasm. Cytoskeleton. Cell junction. Focal adhesion. Cytoplasmic vesicle. Secretory vesicle. Acrosome.

Miscellaneous. Tyrosine phosphatase activity has not been demonstrated for this protein to date.

Similarity. Belongs to the protein-tyrosine phosphatase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q76I76-1	1, L	yes
Q76I76-2	2
Q76I76-3	3, A
Q76I76-4	4

RefSeq proteins (4): NP_001269058, NP_001269059, NP_001269060, NP_203747 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000340	Dual-sp_phosphatase_cat-dom	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR014876	DEK_C	Domain
IPR016130	Tyr_Pase_AS	Active_site
IPR020422	TYR_PHOSPHATASE_DUAL_dom	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR043587	Phosphatase_SSH-like	Family
IPR043588	SSH-N	Domain

Pfam: PF00782, PF08766, PF23040

Catalyzed reactions (Rhea), 3 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)
• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)

UniProt features (56 total): region of interest 11, modified residue 10, compositionally biased region 8, strand 7, helix 7, splice variant 5, sequence variant 3, domain 2, chain 1, active site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2NT2	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q76I76-F1	48.61	0.14

Functional residue map

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

Catalytic / active sites (1): 392 (phosphocysteine intermediate)

Post-translational modifications (10): 17, 25, 36, 461, 487, 534, 631, 633, 1217, 1422

Mutagenesis-validated functional residues (1):

Position	Phenotype
392	abrogates phosphatase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (6): protein dephosphorylation (GO:0006470), spermatogenesis (GO:0007283), actin cytoskeleton organization (GO:0030036), cell differentiation (GO:0030154), negative regulation of actin filament polymerization (GO:0030837), dephosphorylation (GO:0016311)

GO Molecular Function (7): actin binding (GO:0003779), phosphoprotein phosphatase activity (GO:0004721), protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine phosphatase activity (GO:0004725), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791)

GO Cellular Component (7): acrosomal vesicle (GO:0001669), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), focal adhesion (GO:0005925), cytoplasmic vesicle (GO:0031410), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphoprotein phosphatase activity	2
dephosphorylation	1
protein modification process	1
developmental process involved in reproduction	1
male gamete generation	1
cytoskeleton organization	1
actin filament-based process	1
cellular developmental process	1
actin filament polymerization	1
regulation of actin filament polymerization	1
negative regulation of protein polymerization	1
negative regulation of cytoskeleton organization	1
negative regulation of supramolecular fiber organization	1
phosphate-containing compound metabolic process	1
cytoskeletal protein binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
phosphoric ester hydrolase activity	1
secretory granule	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1
cell-substrate junction	1
cytoplasm	1
intracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

1652 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SSH2	CFL1	P23528	868
SSH2	CFL2	Q9Y281	865
SSH2	LIMK1	P53667	865
SSH2	RNF135	Q8IUD6	760
SSH2	FHDC1	Q9C0D6	682
SSH2	EVI2B	P34910	636
SSH2	EVI2A	P22794	584
SSH2	PDXP	Q96GD0	522
SSH2	PHACTR4	Q8IZ21	515
SSH2	CAMK2D	Q13557	486
SSH2	ADAP2	Q9NPF8	486
SSH2	EPHB2	P29323	475
SSH2	BOD1L1	Q8NFC6	471
SSH2	C1orf159	Q96HA4	471
SSH2	TESK1	Q15569	463

IntAct

50 interactions, top by confidence:

A	B	Type	Score
KIF3A	KIF3B	psi-mi:“MI:0914”(association)	0.840
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
DBN1	SVIL	psi-mi:“MI:0914”(association)	0.530
SSH1	GSN	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
SSH2	HECTD1	psi-mi:“MI:0915”(physical association)	0.400
SSH2	rep	psi-mi:“MI:0915”(physical association)	0.370
MYH9	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ANLN	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MYO18A	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MYO19	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
FLNA	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Lima1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
LIMA1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Calml3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Tmod3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Coro1c	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
DBN1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
SYNPO	LMO7	psi-mi:“MI:0914”(association)	0.350
Myh9	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Myo1c	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MYH9	NAP1L1	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): SSH2 (Affinity Capture-MS), SSH2 (Affinity Capture-MS), SSH2 (Affinity Capture-MS), SSH2 (Affinity Capture-MS), SSH2 (Affinity Capture-MS), SSH2 (Affinity Capture-MS), SSH2 (Affinity Capture-MS), SSH2 (Affinity Capture-MS), SSH2 (Affinity Capture-MS), SSH2 (Affinity Capture-MS), SSH2 (Affinity Capture-MS), SSH2 (Affinity Capture-MS), SSH2 (Affinity Capture-MS), SSH2 (Affinity Capture-MS), SSH2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTS1, A0A1B0GWH4, A1A4L6, A1YGI6, A6NDR6, B8QB46, F1MJR8, F1QDF8, O35892, O35893, P09015, P15036, P15037, P23497, P52729, P59598, Q32NH9, Q3KRF1, Q3UM89, Q4G112, Q4V7E1, Q5M7N6, Q5ND04, Q5XIV2, Q5ZHX5, Q66IG8, Q6P1R3, Q6PCX9, Q6PJQ5, Q708W2, Q76I76, Q76I79, Q76N89, Q7M6U3, Q8AXQ4, Q8BVK9, Q8IUE0, Q8IUE1, Q8IWB6, Q8IXJ9

Diamond homologs: A4IHU7, F1QWM2, O09112, O13632, O55737, O95147, P0C591, P0C592, P0C593, P0C594, P0C595, P0C596, P0C597, P0C598, P0C599, P0C5A0, P0C5A1, P0C5A2, P28562, P28563, P51452, Q05922, Q13115, Q13202, Q148W8, Q16828, Q16829, Q17QJ3, Q17QM8, Q1LWL2, Q29RA3, Q2KJ36, Q39491, Q4KL92, Q4RQD3, Q4V7N3, Q54T76, Q54Y32, Q556Y8, Q55BI8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SSH2	“up-regulates activity”	CFL1	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 42 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	183.8×	1e-13
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	162.2×	2e-13
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	162.2×	2e-13
Activation of BH3-only proteins	7	119.8×	2e-12
RHO GTPases activate PKNs	9	98.5×	2e-14
Intrinsic Pathway for Apoptosis	7	70.7×	1e-10
FOXO-mediated transcription	5	57.9×	2e-07
Translocation of SLC2A4 (GLUT4) to the plasma membrane	10	53.2×	1e-13

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	53.9×	5e-06
intracellular protein localization	7	21.6×	5e-06
cilium assembly	5	10.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	150
Likely benign	7
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

5696 predictions. Top by Δscore:

Variant	Effect	Δscore
17:29627511:T:C	acceptor_gain	1.0000
17:29635963:TTTAC:T	donor_loss	1.0000
17:29635964:TTACC:T	donor_loss	1.0000
17:29635965:TACCT:T	donor_loss	1.0000
17:29636803:C:CC	acceptor_gain	1.0000
17:29648358:T:TC	acceptor_gain	1.0000
17:29650648:A:AC	donor_gain	1.0000
17:29650649:C:CC	donor_gain	1.0000
17:29650649:CTCA:C	donor_gain	1.0000
17:29650650:TCA:T	donor_loss	1.0000
17:29650651:CA:C	donor_loss	1.0000
17:29650652:A:AC	donor_gain	1.0000
17:29650652:ACT:A	donor_loss	1.0000
17:29650653:C:CG	donor_gain	1.0000
17:29650653:CT:C	donor_gain	1.0000
17:29650653:CTT:C	donor_gain	1.0000
17:29650653:CTTT:C	donor_gain	1.0000
17:29650653:CTTTG:C	donor_gain	1.0000
17:29650797:TACC:T	acceptor_gain	1.0000
17:29650799:CC:C	acceptor_gain	1.0000
17:29650800:CC:C	acceptor_gain	1.0000
17:29655559:AC:A	donor_gain	1.0000
17:29655560:CC:C	donor_gain	1.0000
17:29666860:AACTT:A	donor_loss	1.0000
17:29666861:ACTT:A	donor_loss	1.0000
17:29666862:CTTAC:C	donor_loss	1.0000
17:29666863:TTACC:T	donor_loss	1.0000
17:29666864:TACCA:T	donor_loss	1.0000
17:29666865:A:AT	donor_loss	1.0000
17:29666866:C:T	donor_loss	1.0000

AlphaMissense

9581 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:29636778:C:A	W457C	1.000
17:29636778:C:G	W457C	1.000
17:29636780:A:G	W457R	1.000
17:29636780:A:T	W457R	1.000
17:29636794:C:G	R452P	1.000
17:29648153:A:C	L446W	1.000
17:29648153:A:G	L446S	1.000
17:29648156:A:C	I445S	1.000
17:29648156:A:G	I445T	1.000
17:29648156:A:T	I445N	1.000
17:29648159:C:T	G444E	1.000
17:29648160:C:A	G444W	1.000
17:29648160:C:G	G444R	1.000
17:29648160:C:T	G444R	1.000
17:29648165:T:C	Y442C	1.000
17:29648166:A:C	Y442D	1.000
17:29648166:A:G	Y442H	1.000
17:29648174:A:G	L439P	1.000
17:29648185:G:C	F435L	1.000
17:29648185:G:T	F435L	1.000
17:29648186:A:C	F435C	1.000
17:29648186:A:G	F435S	1.000
17:29648187:A:G	F435L	1.000
17:29648198:G:T	P431H	1.000
17:29648253:A:G	W413R	1.000
17:29648253:A:T	W413R	1.000
17:29648274:A:C	Y406D	1.000
17:29648276:G:T	A405D	1.000
17:29648291:G:T	A400D	1.000
17:29648298:G:T	R398S	1.000

dbSNP variants (sampled 300 via entrez): RS1000001681 (17:29932190 A>C), RS1000024923 (17:29930338 G>T), RS1000041584 (17:29872719 G>A), RS1000085825 (17:29821880 G>A,C), RS1000129330 (17:29823748 G>A), RS1000136998 (17:29731829 C>A), RS1000141328 (17:29754241 T>A), RS1000142728 (17:29772217 T>C), RS1000146532 (17:29803418 CA>C), RS1000151751 (17:29700389 T>C), RS1000154784 (17:29632948 G>C,T), RS1000161239 (17:29872769 G>A), RS1000171460 (17:29854797 A>T), RS1000174842 (17:29654504 C>T), RS1000178594 (17:29770103 T>G)

Disease associations

OMIM: gene MIM:606779 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST002650_7	Coffee consumption (cups per day)	3.000000e-08
GCST004610_153	White blood cell count	5.000000e-10
GCST004625_240	Monocyte count	2.000000e-17
GCST004627_171	Lymphocyte count	3.000000e-09
GCST006288_285	Heel bone mineral density	1.000000e-15
GCST006288_356	Heel bone mineral density	2.000000e-07
GCST006288_52	Heel bone mineral density	3.000000e-09
GCST007430_132	Peak expiratory flow	2.000000e-14
GCST007431_129	Lung function (FEV1/FVC)	5.000000e-42
GCST010703_115	Brain morphology (MOSTest)	1.000000e-28
GCST010796_5176	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_5177	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST90000025_578	Appendicular lean mass	1.000000e-24
GCST90002383_65	Hematocrit	4.000000e-09
GCST90002384_409	Hemoglobin	2.000000e-09
GCST90002388_492	Lymphocyte count	4.000000e-16
GCST90002393_515	Monocyte count	1.000000e-53
GCST90002394_519	Monocyte percentage of white cells	6.000000e-20
GCST90002398_267	Neutrophil count	2.000000e-15
GCST90002403_356	Red blood cell count	7.000000e-09
GCST90002407_128	White blood cell count	6.000000e-32

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004330	coffee consumption
EFO:0006782	cups of coffee per day measurement
EFO:0005091	monocyte count
EFO:0004587	lymphocyte count
EFO:0009270	heel bone mineral density
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0004346	neuroimaging measurement
EFO:0004327	electrocardiography
EFO:0004980	appendicular lean mass
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3351198 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Formaldehyde	decreases expression	3
sodium arsenite	affects expression, increases expression	2
Acetaminophen	decreases expression, increases expression	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	affects phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
bisphenol S	increases methylation	1
jinfukang	decreases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Dexamethasone	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Ethyl Methanesulfonate	increases expression	1
Ivermectin	decreases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Valproic Acid	decreases methylation	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3386719	Binding	Inhibition of SSH2 (unknown origin) assessed as reduction in pNPP hydrolysis	Fast identification of novel lymphoid tyrosine phosphatase inhibitors using target-ligand interaction-based virtual screening. — J Med Chem

Clinical trials (associated diseases)

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