PLEKHS1

Summary

PLEKHS1 (pleckstrin homology domain containing S1, HGNC:26285) is a protein-coding gene on chromosome 10q25.3, encoding Pleckstrin homology domain-containing family S member 1 (Q5SXH7).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 99 total
• MANE Select transcript: NM_001395068

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26285
Approved symbol	PLEKHS1
Name	pleckstrin homology domain containing S1
Location	10q25.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23537, bA211N11.2
Ensembl gene	ENSG00000148735
Ensembl biotype	protein_coding
Entrez	79949

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000361048, ENST00000369309, ENST00000369310, ENST00000369312, ENST00000448805, ENST00000619563, ENST00000650852, ENST00000652564, ENST00000694986, ENST00000694987

RefSeq mRNA: 5 — MANE Select: NM_001395068 NM_001193434, NM_001193435, NM_001395068, NM_024889, NM_182601

CCDS: CCDS53580, CCDS53581, CCDS7583, CCDS91351

Canonical transcript exons

ENST00000694986 — 13 exons

Exon	Start	End
ENSE00000987115	113774826	113775035
ENSE00001403702	113768815	113768890
ENSE00001407879	113769784	113769900
ENSE00001513943	113755259	113755305
ENSE00001653958	113775765	113775866
ENSE00001737336	113777124	113777259
ENSE00003518894	113766411	113766499
ENSE00003570794	113771970	113772089
ENSE00003581722	113766612	113766718
ENSE00003612643	113774227	113774333
ENSE00003634837	113767345	113767479
ENSE00003847160	113751682	113751761
ENSE00003961462	113780602	113783429

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 97.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5399 / max 99.5197, expressed in 101 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107139	0.2093	50
107136	0.1367	20
107138	0.1217	49
107137	0.0723	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	97.99	gold quality
bronchial epithelial cell	CL:0002328	96.46	gold quality
epithelium of bronchus	UBERON:0002031	95.29	gold quality
bronchus	UBERON:0002185	94.65	gold quality
nasal cavity mucosa	UBERON:0001826	93.63	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.03	gold quality
body of pancreas	UBERON:0001150	92.03	gold quality
nasal cavity epithelium	UBERON:0005384	90.93	gold quality
minor salivary gland	UBERON:0001830	89.61	gold quality
saliva-secreting gland	UBERON:0001044	88.64	gold quality
right uterine tube	UBERON:0001302	87.49	gold quality
palpebral conjunctiva	UBERON:0001812	87.42	gold quality
epithelium of nasopharynx	UBERON:0001951	86.31	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.39	gold quality
small intestine	UBERON:0002108	83.44	gold quality
mouth mucosa	UBERON:0003729	83.17	gold quality
pancreas	UBERON:0001264	81.74	gold quality
trachea	UBERON:0003126	80.06	gold quality
jejunal mucosa	UBERON:0000399	79.56	gold quality
duodenum	UBERON:0002114	79.37	gold quality
parotid gland	UBERON:0001831	78.04	gold quality
rectum	UBERON:0001052	73.31	gold quality
vermiform appendix	UBERON:0001154	72.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	72.36	silver quality
gall bladder	UBERON:0002110	70.01	gold quality
endocervix	UBERON:0000458	69.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.97	gold quality
caecum	UBERON:0001153	68.00	gold quality
prostate gland	UBERON:0002367	67.26	gold quality
left uterine tube	UBERON:0001303	66.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	43.57
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting PLEKHS1, 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-12118	100.00	65.88	1270
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777

Literature-anchored findings (GeneRIF, showing 2)

• this gene is involved in the mild elevation of blood glucose levels and insulin resistance in obesity. (PMID:27523322)
• Risk Stratification Using a Novel Genetic Classifier Including PLEKHS1 Promoter Mutations for Differentiated Thyroid Cancer with Distant Metastasis. (PMID:32326836)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	plekhs1.2	ENSDARG00000070041
danio_rerio	plekhs1.1	ENSDARG00000079227
danio_rerio	plekhs1.3	ENSDARG00000090526
danio_rerio	plekhs1.4	ENSDARG00000096786
mus_musculus	Plekhs1	ENSMUSG00000035818
rattus_norvegicus	Plekhs1	ENSRNOG00000072172
drosophila_melanogaster	dos	FBGN0016794
caenorhabditis_elegans		WBGENE00004928

Paralogs (7): PHLDB1 (ENSG00000019144), GAB2 (ENSG00000033327), GAB1 (ENSG00000109458), PHLDB2 (ENSG00000144824), GAB3 (ENSG00000160219), PHLDB3 (ENSG00000176531), GAB4 (ENSG00000215568)

Protein

Protein identifiers

Pleckstrin homology domain-containing family S member 1 — Q5SXH7 (reviewed: Q5SXH7)

Alternative names: Epididymis luminal protein 185

All UniProt accessions (5): Q5SXH7, A0A384P5Z2, A0A494C040, A0A494C1H5, H7BZQ2

UniProt curated annotations — full annotation on UniProt →

Isoforms (6)

UniProt ID	Names	Canonical?
Q5SXH7-5	5	yes
Q5SXH7-1	1
Q5SXH7-2	2
Q5SXH7-3	3
Q5SXH7-4	4
Q5SXH7-6	6

RefSeq proteins (5): NP_001180363, NP_001180364, NP_001381997, NP_079165, NP_872407 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR042986	PLEKHS1	Family

Pfam: PF00169

UniProt features (15 total): splice variant 7, region of interest 2, compositionally biased region 2, chain 1, domain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5SXH7-F1	59.18	0.18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 105 (showing top): GOZGIT_ESR1_TARGETS_DN, NFKB_Q6, WTGAAAT_UNKNOWN, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, RYTTCCTG_ETS2_B, YNGTTNNNATT_UNKNOWN, chr10q25, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MIKKELSEN_MCV6_LCP_WITH_H3K4ME3, TURASHVILI_BREAST_NORMAL_DUCTAL_VS_LOBULAR_UP, LEE_BMP2_TARGETS_UP

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

360 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLEKHS1	WDR74	Q6RFH5	755
PLEKHS1	TBC1D12	O60347	671
PLEKHS1	LEPROTL1	O95214	540
PLEKHS1	TERT	O14746	507
PLEKHS1	VTI1A	Q96AJ9	476
PLEKHS1	NHLRC2	Q8NBF2	475
PLEKHS1	CCDC186	Q7Z3E2	474
PLEKHS1	DPH3	Q96FX2	467
PLEKHS1	TECTB	Q96PL2	461
PLEKHS1	RBPMS2	Q6ZRY4	460
PLEKHS1	ZDHHC6	Q9H6R6	456
PLEKHS1	ANKRD53	Q8N9V6	447
PLEKHS1	ADGRG6	Q86SQ4	447
PLEKHS1	SDHD	O14521	447
PLEKHS1	TMEM89	A2RUT3	445

IntAct

5 interactions, top by confidence:

A	B	Type	Score
PLEKHS1	PBLD	psi-mi:“MI:0915”(physical association)	0.590
PIK3R3	PLEKHS1	psi-mi:“MI:0915”(physical association)	0.370
PLEKHS1	GRB2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (10): PLEKHS1 (Two-hybrid), PLEKHS1 (Two-hybrid), GRB2 (Affinity Capture-Luminescence), PIK3R3 (Affinity Capture-Luminescence), PBLD (Affinity Capture-MS), PLEKHS1 (Two-hybrid), TCP11L1 (Two-hybrid), PBLD (Affinity Capture-MS), PLEKHS1 (Affinity Capture-MS), PLEKHS1 (Affinity Capture-MS)

ESM2 similar proteins: A0A5K7RLP0, A1YEX3, A7YWH3, B1WBU4, O15151, O35618, O43298, O88850, P24278, P97303, Q01954, Q0V8G8, Q15916, Q17RG1, Q562E2, Q5RC05, Q5RDQ6, Q5SXH7, Q5TC79, Q5VYS8, Q5W0Q7, Q5XIN1, Q6ZPY5, Q6ZSB9, Q6ZU67, Q7ZUW7, Q7ZYI3, Q8BLK9, Q8BSV3, Q8IW35, Q8K088, Q8N680, Q8N7W2, Q8TCN5, Q8VHI4, Q8WW38, Q90W33, Q96BR9, Q96S38, Q99ME3

Diamond homologs: Q5SXH7, Q8BW88

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1953 predictions. Top by Δscore:

Variant	Effect	Δscore
10:113766719:G:GG	donor_gain	1.0000
10:113766735:G:GT	donor_gain	1.0000
10:113766736:A:T	donor_gain	1.0000
10:113772048:G:GT	donor_gain	1.0000
10:113774225:A:AG	acceptor_gain	1.0000
10:113774225:AGTT:A	acceptor_gain	1.0000
10:113774225:AGTTG:A	acceptor_gain	1.0000
10:113774226:G:GG	acceptor_gain	1.0000
10:113774226:GT:G	acceptor_gain	1.0000
10:113774226:GTT:G	acceptor_gain	1.0000
10:113774226:GTTG:G	acceptor_gain	1.0000
10:113774226:GTTGG:G	acceptor_gain	1.0000
10:113774330:CCTA:C	donor_gain	1.0000
10:113774334:G:GG	donor_gain	1.0000
10:113775764:GTAAT:G	acceptor_gain	1.0000
10:113755397:G:GA	donor_gain	0.9900
10:113766714:GATCA:G	donor_gain	0.9900
10:113771966:TCA:T	acceptor_loss	0.9900
10:113771968:A:AG	acceptor_gain	0.9900
10:113771968:AGC:A	acceptor_loss	0.9900
10:113771969:G:GA	acceptor_gain	0.9900
10:113771969:GC:G	acceptor_gain	0.9900
10:113771969:GCAT:G	acceptor_gain	0.9900
10:113771969:GCATT:G	acceptor_gain	0.9900
10:113771972:T:G	acceptor_gain	0.9900
10:113772073:G:GT	donor_gain	0.9900
10:113772085:TAGAG:T	donor_loss	0.9900
10:113772086:AGAG:A	donor_loss	0.9900
10:113772087:GAGGT:G	donor_loss	0.9900
10:113772088:AG:A	donor_loss	0.9900

AlphaMissense

3102 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:113766469:A:C	K23N	0.998
10:113766469:A:T	K23N	0.998
10:113766618:T:A	W36R	0.997
10:113766618:T:C	W36R	0.997
10:113766620:G:C	W36C	0.995
10:113766620:G:T	W36C	0.995
10:113766467:A:G	K23E	0.994
10:113766468:A:T	K23I	0.991
10:113766619:G:C	W36S	0.991
10:113766622:A:T	K37I	0.991
10:113766623:A:C	K37N	0.991
10:113766623:A:T	K37N	0.991
10:113768831:T:A	W120R	0.991
10:113768831:T:C	W120R	0.991
10:113777134:T:A	W348R	0.990
10:113777134:T:C	W348R	0.990
10:113766467:A:C	K23Q	0.989
10:113766633:T:C	F41L	0.984
10:113766635:C:A	F41L	0.984
10:113766635:C:G	F41L	0.984
10:113766468:A:C	K23T	0.983
10:113766628:G:C	R39P	0.983
10:113767453:G:C	R105S	0.983
10:113767453:G:T	R105S	0.983
10:113767464:T:C	L109P	0.983
10:113766470:T:C	S24P	0.982
10:113766634:T:C	F41S	0.982
10:113767428:T:A	V97D	0.982
10:113767406:T:C	F90L	0.981
10:113767408:T:A	F90L	0.981

dbSNP variants (sampled 300 via entrez): RS1000075483 (10:113778457 T>A,C), RS1000145928 (10:113777735 G>A), RS1000323506 (10:113772158 T>C,G), RS1000448111 (10:113777984 T>C), RS1000507821 (10:113765615 A>G), RS1000520009 (10:113760428 A>G), RS1000690443 (10:113771694 A>T), RS1000894032 (10:113753522 G>A), RS1001013816 (10:113783089 G>C), RS1001145341 (10:113772048 G>A), RS1001237544 (10:113759899 T>C), RS1001271469 (10:113759480 ACTGT>A), RS1001372134 (10:113749812 T>C), RS1001421501 (10:113750156 T>A,C), RS1001490356 (10:113783707 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001762_827	Obesity-related traits	1.000000e-06
GCST009391_1754	Metabolite levels	9.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004730	hormone measurement
EFO:0010369	lysophosphatidylethanolamine 18:2 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression	2
propionaldehyde	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
terbufos	increases methylation	1
sodium arsenite	decreases methylation, increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
gallium arsenide	decreases expression	1
abrine	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	increases abundance, decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Dust	decreases expression, increases abundance	1
Fonofos	increases methylation	1
Estradiol	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Parathion	increases methylation	1
Phthalic Acids	increases methylation	1
Tretinoin	increases expression	1
Okadaic Acid	increases expression	1
Raloxifene Hydrochloride	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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