PLEKHH3

Summary

PLEKHH3 (pleckstrin homology, MyTH4 and FERM domain containing H3, HGNC:26105) is a protein-coding gene on chromosome 17q21.2, encoding Pleckstrin homology domain-containing family H member 3 (Q7Z736).

Located in extracellular space.

Source: NCBI Gene 79990 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 155 total
• MANE Select transcript: NM_024927

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26105
Approved symbol	PLEKHH3
Name	pleckstrin homology, MyTH4 and FERM domain containing H3
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21019
Ensembl gene	ENSG00000068137
Ensembl biotype	protein_coding
Entrez	79990

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 11 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000293349, ENST00000456950, ENST00000587627, ENST00000591022, ENST00000591196, ENST00000591476, ENST00000591490, ENST00000591544, ENST00000592974, ENST00000895611, ENST00000895612, ENST00000917129, ENST00000949018, ENST00000949019, ENST00000949020, ENST00000949021, ENST00000949022

RefSeq mRNA: 2 — MANE Select: NM_024927 NM_001411112, NM_024927

CCDS: CCDS11434, CCDS92327

Canonical transcript exons

ENST00000591022 — 13 exons

Exon	Start	End
ENSE00001059185	42670994	42671130
ENSE00001219920	42669918	42670376
ENSE00002911635	42676402	42676994
ENSE00003459445	42673399	42673556
ENSE00003460340	42671351	42671558
ENSE00003494715	42673934	42674013
ENSE00003515204	42670573	42670705
ENSE00003559406	42669430	42669621
ENSE00003569850	42673643	42673834
ENSE00003571802	42672086	42672392
ENSE00003621493	42673176	42673296
ENSE00003625767	42667914	42668303
ENSE00003641161	42674354	42674409

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 97.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.5444 / max 111.1305, expressed in 1564 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166176	7.1551	1499
166177	1.8168	1115
166174	0.3062	137
166175	0.2663	119

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.28	gold quality
body of pancreas	UBERON:0001150	96.64	gold quality
right coronary artery	UBERON:0001625	93.59	gold quality
esophagus mucosa	UBERON:0002469	93.30	gold quality
ectocervix	UBERON:0012249	93.23	gold quality
body of stomach	UBERON:0001161	92.87	gold quality
apex of heart	UBERON:0002098	92.30	gold quality
endocervix	UBERON:0000458	92.14	gold quality
left uterine tube	UBERON:0001303	91.74	gold quality
tibial artery	UBERON:0007610	91.46	gold quality
popliteal artery	UBERON:0002250	91.45	gold quality
descending thoracic aorta	UBERON:0002345	91.29	gold quality
ascending aorta	UBERON:0001496	91.19	gold quality
right ovary	UBERON:0002118	91.15	gold quality
aorta	UBERON:0000947	91.12	gold quality
thoracic aorta	UBERON:0001515	91.08	gold quality
adenohypophysis	UBERON:0002196	90.76	gold quality
mucosa of stomach	UBERON:0001199	90.72	gold quality
left coronary artery	UBERON:0001626	90.43	gold quality
esophagus	UBERON:0001043	90.40	gold quality
body of uterus	UBERON:0009853	90.23	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.08	gold quality
left ovary	UBERON:0002119	89.92	gold quality
right adrenal gland	UBERON:0001233	89.88	gold quality
skin of abdomen	UBERON:0001416	89.65	gold quality
right adrenal gland cortex	UBERON:0035827	89.65	gold quality
left adrenal gland cortex	UBERON:0035825	89.44	gold quality
skin of leg	UBERON:0001511	89.37	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.31	gold quality
gastrocnemius	UBERON:0001388	89.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting PLEKHH3, 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-4455	100.00	65.48	1587
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-609	99.82	64.26	505
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-708-3P	97.50	68.67	1082
HSA-MIR-6748-3P	97.20	65.66	836
HSA-MIR-6895-5P	97.05	64.96	522
HSA-MIR-339-5P	96.73	66.01	820

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	PLEKHH3	ENSDARG00000070174
mus_musculus	Plekhh3	ENSMUSG00000035172
rattus_norvegicus	Plekhh3	ENSRNOG00000020238

Protein

Protein identifiers

Pleckstrin homology domain-containing family H member 3 — Q7Z736 (reviewed: Q7Z736)

All UniProt accessions (3): Q7Z736, K7EK04, X6R3U4

UniProt curated annotations — full annotation on UniProt →

Isoforms (4)

UniProt ID	Names	Canonical?
Q7Z736-1	1	yes
Q7Z736-2	2
Q7Z736-3	3
Q7Z736-4	4

RefSeq proteins (2): NP_001398041, NP_079203* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000299	FERM_domain	Domain
IPR000857	MyTH4_dom	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR014352	FERM/acyl-CoA-bd_prot_sf	Homologous_superfamily
IPR019748	FERM_central	Domain
IPR019749	Band_41_domain	Domain
IPR035963	FERM_2	Homologous_superfamily
IPR038185	MyTH4_dom_sf	Homologous_superfamily
IPR051724	Actin_motor_Myosin	Family

Pfam: PF00373, PF00784, PF21989

UniProt features (26 total): splice variant 7, compositionally biased region 4, region of interest 4, modified residue 3, domain 3, sequence conflict 2, signal peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z736-F1	74.53	0.43

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 (3): 30, 638, 642

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 100 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, AP1_01, PAX4_01, GCANCTGNY_MYOD_Q6, TTTGTAG_MIR520D, AREB6_03, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, CREBP1_Q2, AP1_Q4_01, TGCTGAY_UNKNOWN, OCT1_03, BACH2_01, ARGGGTTAA_UNKNOWN, TGANTCA_AP1_C, NRF2_Q4

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (2): obsolete extracellular space (GO:0005615), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	1

Protein interactions and networks

STRING

728 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLEKHH3	WDR49	Q8IV35	577
PLEKHH3	GRIFIN	A4D1Z8	483
PLEKHH3	IFT70A	Q86WT1	458
PLEKHH3	PROB1	E7EW31	458
PLEKHH3	FAM151A	Q8WW52	454
PLEKHH3	ASB15	Q8WXK1	454
PLEKHH3	FRMD7	Q6ZUT3	453
PLEKHH3	NUAK2	Q9H093	399
PLEKHH3	HEATR5B	Q9P2D3	398
PLEKHH3	CNIH1	O95406	387
PLEKHH3	PLEKHA2	Q9HB19	383
PLEKHH3	PLEKHG1	Q9ULL1	382
PLEKHH3	LMOD2	Q6P5Q4	377
PLEKHH3	PLEKHB2	Q96CS7	372
PLEKHH3	ZNF875	P10072	353

IntAct

71 interactions, top by confidence:

A	B	Type	Score
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
GNAI3	RGS12	psi-mi:“MI:0914”(association)	0.640
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
EFNB2	FAM171A2	psi-mi:“MI:0914”(association)	0.530
TGFBR2	PIK3R2	psi-mi:“MI:0914”(association)	0.530
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
IL4R	RHOBTB3	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
PTGES3	AIP	psi-mi:“MI:0914”(association)	0.530
TMEM200A	STX6	psi-mi:“MI:0914”(association)	0.530
CTDSP2	ZMYM6	psi-mi:“MI:0914”(association)	0.530
GABARAPL2	PLEKHH3	psi-mi:“MI:0407”(direct interaction)	0.440
PLEKHH3	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
PB1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAPK4	ILVBL	psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PTGES3	SBNO1	psi-mi:“MI:0914”(association)	0.350
AVPR1B	KLRG2	psi-mi:“MI:0914”(association)	0.350
EFNB1	KRBA1	psi-mi:“MI:0914”(association)	0.350
MAGEA8	METTL15	psi-mi:“MI:0914”(association)	0.350
CX3CL1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
SKAP1	MYO9A	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350

BioGRID (77): PLEKHH3 (Affinity Capture-MS), PLEKHH3 (Affinity Capture-MS), PLEKHH3 (Affinity Capture-MS), PLEKHH3 (Affinity Capture-MS), PLEKHH3 (Affinity Capture-MS), PLEKHH3 (Affinity Capture-MS), PLEKHH3 (Affinity Capture-MS), PLEKHH3 (Affinity Capture-MS), PLEKHH3 (Affinity Capture-MS), PLEKHH3 (Affinity Capture-MS), PLEKHH3 (Affinity Capture-MS), PLEKHH3 (Affinity Capture-MS), PLEKHH3 (Affinity Capture-MS), PLEKHH3 (Affinity Capture-MS), PLEKHH3 (Affinity Capture-MS)

ESM2 similar proteins: A1L515, A4D2P6, A6QQD2, A8VU90, E1BDF2, O75808, O88995, P0CG25, P22083, Q0IIA6, Q2TA57, Q3B7L1, Q3MIP1, Q3U5Q7, Q3UR50, Q3UR97, Q3UV16, Q400G9, Q5BKX5, Q5EBM0, Q5GH72, Q5SZI1, Q5TM19, Q5U4P2, Q62994, Q659K9, Q6PRD1, Q7Z736, Q861W0, Q86UR1, Q8BNN1, Q8C0R7, Q8CG70, Q8IUW3, Q8IVL6, Q8N398, Q8NAG6, Q8NCW0, Q8R2H1, Q8VCE9

Diamond homologs: A0MP03, A5PF48, B2RTY4, D3ZJP6, E1BPK6, E7EZG2, E9Q634, F4HWY6, F4HXP9, F4I460, F4I507, F4I5Q6, F4IRU3, F4IUG9, F4IVR7, F4JM19, F4K0A6, F4K5J1, F8VQB6, K7U9N8, O00159, O00160, O08638, O74805, O88329, O94477, P05659, P08799, P10587, P19524, P21271, P22467, P24733, P32492, P34092, P34109, P35580, P35748, P35749, P42522

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	137
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2109 predictions. Top by Δscore:

Variant	Effect	Δscore
17:42669621:CCTG:C	acceptor_loss	1.0000
17:42669622:CTGCA:C	acceptor_loss	1.0000
17:42669623:T:C	acceptor_loss	1.0000
17:42669926:G:C	donor_gain	1.0000
17:42670992:A:AC	donor_gain	1.0000
17:42670993:C:CC	donor_gain	1.0000
17:42670993:CTT:C	donor_gain	1.0000
17:42670995:T:TA	donor_gain	1.0000
17:42671126:GCCAC:G	acceptor_gain	1.0000
17:42671127:CCAC:C	acceptor_gain	1.0000
17:42671127:CCACC:C	acceptor_gain	1.0000
17:42671128:CAC:C	acceptor_gain	1.0000
17:42671128:CACC:C	acceptor_gain	1.0000
17:42671129:AC:A	acceptor_gain	1.0000
17:42671130:CC:C	acceptor_gain	1.0000
17:42671131:C:A	acceptor_loss	1.0000
17:42671131:C:CC	acceptor_gain	1.0000
17:42671352:T:TA	donor_gain	1.0000
17:42671353:C:A	donor_gain	1.0000
17:42671557:TC:T	acceptor_gain	1.0000
17:42671558:CC:C	acceptor_gain	1.0000
17:42671730:A:AC	donor_gain	1.0000
17:42671731:C:CC	donor_gain	1.0000
17:42673386:C:CA	donor_gain	1.0000
17:42673394:TGTA:T	donor_loss	1.0000
17:42673395:GTAC:G	donor_loss	1.0000
17:42673396:TA:T	donor_loss	1.0000
17:42673397:ACC:A	donor_loss	1.0000
17:42673552:CAGAC:C	acceptor_gain	1.0000
17:42673557:C:A	acceptor_loss	1.0000

AlphaMissense

4981 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:42672232:C:A	K310N	0.998
17:42672232:C:G	K310N	0.998
17:42671466:G:T	P390H	0.997
17:42672290:A:T	L291H	0.997
17:42672142:G:C	S340R	0.996
17:42672142:G:T	S340R	0.996
17:42672144:T:G	S340R	0.996
17:42673762:A:T	L124H	0.996
17:42671466:G:C	P390R	0.995
17:42672239:A:G	L308P	0.995
17:42672349:G:C	F271L	0.995
17:42672349:G:T	F271L	0.995
17:42672351:A:G	F271L	0.995
17:42673477:C:A	W190C	0.995
17:42673477:C:G	W190C	0.995
17:42673479:A:G	W190R	0.995
17:42673479:A:T	W190R	0.995
17:42671478:C:A	R386I	0.994
17:42672290:A:G	L291P	0.994
17:42673208:A:T	L246H	0.994
17:42673241:A:G	L235P	0.994
17:42673415:A:G	L211P	0.994
17:42673762:A:G	L124P	0.994
17:42672234:T:C	K310E	0.993
17:42673241:A:T	L235Q	0.993
17:42673693:A:T	L147H	0.993
17:42669436:G:C	S733R	0.992
17:42669436:G:T	S733R	0.992
17:42669438:T:G	S733R	0.992
17:42672158:A:G	L335P	0.992

dbSNP variants (sampled 300 via entrez): RS1000189149 (17:42668552 G>C,T), RS1000284310 (17:42678731 C>A,T), RS1000558015 (17:42667517 C>A,G), RS1000615881 (17:42675917 T>A,C), RS1000645761 (17:42668813 T>C), RS1000967461 (17:42674066 C>T), RS1001550579 (17:42669774 C>A,T), RS1001626400 (17:42675565 GGCCCCGGCGGCGCAGCCC>G), RS1002115991 (17:42677031 G>C,T), RS1002428507 (17:42675518 C>A,G), RS1003118722 (17:42678110 C>A,G), RS1003160202 (17:42670496 T>G), RS1003352625 (17:42675737 C>A,G,T), RS1003583154 (17:42672005 G>A), RS1003908161 (17:42669411 A>G,T)

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
GCST008529_19	Tea consumption	2.000000e-06
GCST009963_16	Cataracts (operation)	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010091	tea consumption measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
benzo(e)pyrene	increases methylation	1
ICG 001	increases 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
Irinotecan	increases expression	1
Fulvestrant	increases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Cisplatin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Formaldehyde	decreases expression	1
Methapyrilene	increases methylation	1
Phthalic Acids	increases methylation	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Tunicamycin	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Thapsigargin	increases expression	1
Copper Sulfate	increases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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