PLEKHH1

Summary

PLEKHH1 (pleckstrin homology, MyTH4 and FERM domain containing H1, HGNC:17733) is a protein-coding gene on chromosome 14q24.1, encoding Pleckstrin homology domain-containing family H member 1 (Q9ULM0).

Predicted to be located in cytoskeleton.

Source: NCBI Gene 57475 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 5 total
• MANE Select transcript: NM_020715

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17733
Approved symbol	PLEKHH1
Name	pleckstrin homology, MyTH4 and FERM domain containing H1
Location	14q24.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1200
Ensembl gene	ENSG00000054690
Ensembl biotype	protein_coding
Entrez	57475

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 11 retained_intron, 5 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000329153, ENST00000557971, ENST00000558214, ENST00000558296, ENST00000558366, ENST00000558386, ENST00000558981, ENST00000559168, ENST00000559766, ENST00000559832, ENST00000559981, ENST00000560100, ENST00000561057, ENST00000561135, ENST00000561370, ENST00000561456, ENST00000870157, ENST00000870158, ENST00000870159, ENST00000931409

RefSeq mRNA: 1 — MANE Select: NM_020715 NM_020715

CCDS: CCDS45128

Canonical transcript exons

ENST00000329153 — 29 exons

Exon	Start	End
ENSE00000807770	67533290	67533398
ENSE00001632224	67569138	67569216
ENSE00001668372	67555825	67555887
ENSE00001710346	67559608	67559691
ENSE00001715153	67562137	67562894
ENSE00001765506	67557269	67557418
ENSE00001767995	67561954	67562035
ENSE00002218188	67541834	67541993
ENSE00002561322	67587074	67589612
ENSE00003463475	67573276	67573386
ENSE00003505419	67574242	67574403
ENSE00003509953	67579721	67579876
ENSE00003542998	67585568	67585654
ENSE00003560464	67580938	67581038
ENSE00003573704	67583741	67583883
ENSE00003576623	67578023	67578199
ENSE00003607211	67577302	67577414
ENSE00003610353	67582069	67582210
ENSE00003612879	67583995	67584124
ENSE00003635544	67575392	67575472
ENSE00003636010	67572135	67572277
ENSE00003636380	67579134	67579311
ENSE00003639127	67585951	67586097
ENSE00003641697	67578534	67578631
ENSE00003651494	67569921	67570012
ENSE00003679177	67575823	67576005
ENSE00003684431	67573801	67573887
ENSE00003690560	67576395	67576503
ENSE00003690827	67571752	67571902

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 99.52.

FANTOM5 (CAGE): breadth broad, TPM avg 7.0234 / max 738.3867, expressed in 772 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140233	3.5008	352
140228	1.4347	546
140229	0.6853	301
140230	0.6795	184
140232	0.5970	94
140231	0.1261	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	99.52	gold quality
inferior vagus X ganglion	UBERON:0005363	99.48	gold quality
left lobe of thyroid gland	UBERON:0001120	99.40	gold quality
lateral globus pallidus	UBERON:0002476	99.31	gold quality
pancreatic ductal cell	CL:0002079	99.29	gold quality
thyroid gland	UBERON:0002046	99.29	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.20	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.19	gold quality
spinal cord	UBERON:0002240	99.16	gold quality
corpus callosum	UBERON:0002336	99.10	gold quality
subthalamic nucleus	UBERON:0001906	99.07	gold quality
medulla oblongata	UBERON:0001896	98.87	gold quality
substantia nigra pars compacta	UBERON:0001965	98.75	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.65	gold quality
ventral tegmental area	UBERON:0002691	98.60	gold quality
globus pallidus	UBERON:0001875	98.55	gold quality
endothelial cell	CL:0000115	98.54	gold quality
superior vestibular nucleus	UBERON:0007227	98.43	gold quality
medial globus pallidus	UBERON:0002477	98.36	gold quality
midbrain	UBERON:0001891	98.28	gold quality
substantia nigra	UBERON:0002038	98.22	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.08	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.01	gold quality
cerebellar hemisphere	UBERON:0002245	97.81	gold quality
cerebellar cortex	UBERON:0002129	97.76	gold quality
putamen	UBERON:0001874	97.52	gold quality
cerebellum	UBERON:0002037	97.45	gold quality
parotid gland	UBERON:0001831	97.42	gold quality
Ammon’s horn	UBERON:0001954	97.02	gold quality
pons	UBERON:0000988	96.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1092.60
E-HCAD-35	yes	72.65
E-HCAD-25	yes	49.93
E-GEOD-84465	yes	9.58
E-ANND-3	yes	6.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

180 targeting PLEKHH1, 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-513A-5P	100.00	69.77	2465
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-3910	99.95	71.13	2227

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	plekhh1	ENSDARG00000053835
mus_musculus	Plekhh1	ENSMUSG00000060716
rattus_norvegicus	Plekhh1	ENSRNOG00000010650
drosophila_melanogaster	CG43867	FBGN0264449
caenorhabditis_elegans		WBGENE00003143

Paralogs (1): PLEKHH2 (ENSG00000152527)

Protein

Protein identifiers

Pleckstrin homology domain-containing family H member 1 — Q9ULM0 (reviewed: Q9ULM0)

All UniProt accessions (4): Q9ULM0, H0YKY5, H0YLU5, H0YMQ6

Isoforms (2)

UniProt ID	Names	Canonical?
Q9ULM0-1	1	yes
Q9ULM0-2	2

RefSeq proteins (1): NP_065766* (*=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

Pfam: PF00169, PF00373, PF00784, PF21989

UniProt features (24 total): sequence variant 6, region of interest 5, domain 4, compositionally biased region 3, splice variant 3, chain 1, coiled-coil region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULM0-F1	70.81	0.33

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 (1): 745

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 117 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GTGCCTT_MIR506, chr14q24, TGCCTTA_MIR124A, HUANG_DASATINIB_RESISTANCE_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, DODD_NASOPHARYNGEAL_CARCINOMA_DN, ACACTGG_MIR199A_MIR199B, WANG_CISPLATIN_RESPONSE_AND_XPC_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN, WAMUNYOKOLI_OVARIAN_CANCER_LMP_UP, DUTERTRE_ESTRADIOL_RESPONSE_6HR_UP, PANGAS_TUMOR_SUPPRESSION_BY_SMAD1_AND_SMAD5_DN, BHAT_ESR1_TARGETS_NOT_VIA_AKT1_UP

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): 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

458 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLEKHH1	C7orf57	Q8NEG2	449
PLEKHH1	SLC16A9	Q7RTY1	434
PLEKHH1	MYC	P01106	416
PLEKHH1	KIAA0408	Q6ZU52	416
PLEKHH1	ZFYVE26	Q68DK2	400
PLEKHH1	RAD51B	O15315	389
PLEKHH1	ABHD18	Q0P651	379
PLEKHH1	ELOVL2	Q9NXB9	379
PLEKHH1	RBPMS2	Q6ZRY4	367
PLEKHH1	TMEM144	Q7Z5S9	345
PLEKHH1	PRR15	Q8IV56	341
PLEKHH1	TMEM217B	A0A494BZU4	340
PLEKHH1	TMEM217	Q8N7C4	336
PLEKHH1	KLHL5	Q96PQ7	335
PLEKHH1	POLR3GL	Q9BT43	333

IntAct

23 interactions, top by confidence:

A	B	Type	Score
BRK1	HSBP1	psi-mi:“MI:0914”(association)	0.740
LPXN	PCNT	psi-mi:“MI:0914”(association)	0.640
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
APBB1IP	ANXA13	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
FKBP5	IFT56	psi-mi:“MI:0914”(association)	0.350
FKBP8	GNB5	psi-mi:“MI:0914”(association)	0.350
PPP4R1L	IFT56	psi-mi:“MI:0914”(association)	0.350
PTGES3	SBNO1	psi-mi:“MI:0914”(association)	0.350
DKK3	MYO9A	psi-mi:“MI:0914”(association)	0.350
BRK1	KIF5C	psi-mi:“MI:0914”(association)	0.350
APBB1IP	ACTA2	psi-mi:“MI:0914”(association)	0.350
LPXN	MED14	psi-mi:“MI:0914”(association)	0.350
MAGEA10	KANSL1L	psi-mi:“MI:0914”(association)	0.350
ARGLU1	PIAS2	psi-mi:“MI:2364”(proximity)	0.270
PLEKHH1		psi-mi:“MI:0915”(physical association)	0.000
CHAF1B	PLEKHH1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): PLEKHH1 (Affinity Capture-MS), PLEKHH1 (Affinity Capture-MS), PLEKHH1 (Affinity Capture-MS), PLEKHH1 (Affinity Capture-RNA), PLEKHH1 (Proximity Label-MS), PLEKHH1 (Affinity Capture-MS), PLEKHH1 (Affinity Capture-MS), PLEKHH1 (Affinity Capture-MS), PLEKHH1 (Affinity Capture-MS), PLEKHH1 (Affinity Capture-MS), PLEKHH1 (Affinity Capture-MS), PLEKHH1 (Affinity Capture-MS), PLEKHH1 (Affinity Capture-MS), PLEKHH1 (Affinity Capture-MS), PLEKHH1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3NFE2, A0FI79, B1AVH7, B5DFA1, D2H0G5, D7PF45, O00750, O15357, O70143, P29353, P97573, P98083, Q00IB7, Q0IIE2, Q15678, Q16825, Q17R13, Q2I6J0, Q2I6J1, Q2V2M9, Q5JV73, Q5M824, Q5R7W7, Q5U2X5, Q61120, Q62130, Q62136, Q62728, Q62925, Q69Z98, Q6P4S2, Q6P549, Q80TI1, Q8AY68, Q8BMC3, Q8BYW1, Q8IWQ3, Q8K245, Q92529, Q92835

Diamond homologs: A1CFB3, A1CYS1, A2QNQ5, A7A179, A7ERM5, A7KAK6, A7KAN4, A7TF84, C4B4E5, I1S8Q3, P0CN90, P0CN91, Q00IB7, Q06321, Q08001, Q0CKU4, Q0UY53, Q2U0C3, Q4WID6, Q54IL5, Q5A950, Q5B4C9, Q6BN88, Q6C8M8, Q6CUV2, Q751Z4, Q7S1I0, Q80TI1, Q8C115, Q8CI52, Q8IVE3, Q8N4B1, Q8NJS1, Q9F2F9, Q9M8Z7, Q9ULM0, Q9XIG1, Q9Y751, Q3KR37, Q3KR56

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

4971 predictions. Top by Δscore:

Variant	Effect	Δscore
14:67541817:T:TA	acceptor_gain	1.0000
14:67541820:A:AG	acceptor_gain	1.0000
14:67541820:AT:A	acceptor_gain	1.0000
14:67541820:ATGCT:A	acceptor_gain	1.0000
14:67541821:T:G	acceptor_gain	1.0000
14:67541821:T:TA	acceptor_gain	1.0000
14:67541824:T:A	acceptor_gain	1.0000
14:67541832:A:AG	acceptor_gain	1.0000
14:67541832:A:C	acceptor_loss	1.0000
14:67541832:AG:A	acceptor_gain	1.0000
14:67541832:AGG:A	acceptor_gain	1.0000
14:67541833:G:GA	acceptor_gain	1.0000
14:67541833:GG:G	acceptor_gain	1.0000
14:67541833:GGG:G	acceptor_gain	1.0000
14:67541833:GGGC:G	acceptor_gain	1.0000
14:67541992:AGG:A	donor_loss	1.0000
14:67541994:G:GG	donor_gain	1.0000
14:67541994:GT:G	donor_loss	1.0000
14:67555814:T:TA	acceptor_gain	1.0000
14:67557265:TCAG:T	acceptor_loss	1.0000
14:67557266:CAGG:C	acceptor_loss	1.0000
14:67557267:A:AT	acceptor_loss	1.0000
14:67557267:AGGT:A	acceptor_gain	1.0000
14:67557267:AGGTG:A	acceptor_gain	1.0000
14:67557268:G:A	acceptor_loss	1.0000
14:67557268:GGT:G	acceptor_gain	1.0000
14:67557268:GGTG:G	acceptor_gain	1.0000
14:67557268:GGTGG:G	acceptor_gain	1.0000
14:67557415:GCAG:G	donor_gain	1.0000
14:67557416:CAGG:C	donor_loss	1.0000

AlphaMissense

8869 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:67574302:T:A	W663R	0.998
14:67574302:T:C	W663R	0.998
14:67576401:T:A	W787R	0.997
14:67576401:T:C	W787R	0.997
14:67577407:T:C	L856P	0.997
14:67578033:T:C	L862P	0.997
14:67578084:T:C	L879P	0.997
14:67578087:C:A	A880D	0.997
14:67578126:T:C	L893P	0.996
14:67578544:T:C	L921P	0.996
14:67573301:T:C	L585P	0.995
14:67573342:T:A	W599R	0.995
14:67573342:T:C	W599R	0.995
14:67577397:G:C	A853P	0.995
14:67578036:T:C	F863S	0.995
14:67578150:T:C	L901P	0.995
14:67579286:T:A	V1001E	0.995
14:67573345:T:C	F600L	0.994
14:67573347:T:A	F600L	0.994
14:67573347:T:G	F600L	0.994
14:67574304:G:C	W663C	0.994
14:67574304:G:T	W663C	0.994
14:67576414:T:C	L791P	0.994
14:67578099:T:C	L884P	0.994
14:67579225:G:A	E981K	0.994
14:67579241:T:C	L986P	0.994
14:67580959:T:A	W1069R	0.994
14:67580959:T:C	W1069R	0.994
14:67555855:G:C	A53P	0.993
14:67575980:T:C	L776P	0.993

dbSNP variants (sampled 300 via entrez): RS1000053876 (14:67534513 ATTG>A), RS1000063970 (14:67546962 G>T), RS1000074186 (14:67536492 A>G), RS1000090398 (14:67540224 G>A), RS1000099512 (14:67570108 T>C), RS1000130537 (14:67548497 A>T), RS1000283168 (14:67572687 G>A), RS1000333285 (14:67542862 G>A), RS1000345995 (14:67559417 G>C), RS1000390503 (14:67567244 G>A,T), RS1000526191 (14:67551761 C>T), RS1000528578 (14:67531350 A>T), RS1000622179 (14:67574001 A>T), RS1000708220 (14:67546688 G>A), RS1000777556 (14:67559215 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

4 associations (top):

Study	Trait	p-value
GCST001414_23	Phospholipid levels (plasma)	9.000000e-18
GCST005342_7	Plasma kynurenine levels in major depressive disorder	5.000000e-06
GCST006627_59	Diastolic blood pressure	8.000000e-10
GCST008928_10	Phosphatidylcholine-ether levels	9.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008529	kynurenine measurement
EFO:0006336	diastolic blood pressure
EFO:0010227	phosphatidylcholine ether measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation, decreases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Nickel	decreases expression	2
Tretinoin	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
titanium dioxide	increases expression	1
sodium arsenite	decreases expression, increases abundance, affects cotreatment	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
(+)-JQ1 compound	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Estradiol	increases expression	1
Manganese	increases abundance, affects cotreatment, decreases expression	1
Quercetin	increases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases expression	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8TC	Ubigene HCT 116 PLEKHH1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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