PLEKHB1

Summary

PLEKHB1 (pleckstrin homology domain containing B1, HGNC:19079) is a protein-coding gene on chromosome 11q13.4, encoding Pleckstrin homology domain-containing family B member 1 (Q9UF11).

Predicted to enable protein homodimerization activity. Predicted to be involved in regulation of cell differentiation. Located in membrane.

Source: NCBI Gene 58473 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 68 total
• MANE Select transcript: NM_021200

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19079
Approved symbol	PLEKHB1
Name	pleckstrin homology domain containing B1
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Aliases	PHR1, KPL1
Ensembl gene	ENSG00000021300
Ensembl biotype	protein_coding
OMIM	607651
Entrez	58473

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 16 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000227214, ENST00000354190, ENST00000398492, ENST00000398494, ENST00000426191, ENST00000535129, ENST00000535582, ENST00000536527, ENST00000538227, ENST00000539157, ENST00000540157, ENST00000540431, ENST00000541597, ENST00000541760, ENST00000542389, ENST00000543085, ENST00000543524, ENST00000544282, ENST00000544532, ENST00000545106, ENST00000545798, ENST00000546251

RefSeq mRNA: 5 — MANE Select: NM_021200 NM_001130033, NM_001130034, NM_001130035, NM_001130036, NM_021200

CCDS: CCDS44672, CCDS44673, CCDS44674, CCDS44675

Canonical transcript exons

ENST00000354190 — 8 exons

Exon	Start	End
ENSE00001062903	73651788	73651890
ENSE00001062905	73652975	73653014
ENSE00001062907	73655803	73655907
ENSE00002231655	73661466	73662819
ENSE00003623782	73649012	73649087
ENSE00003647908	73660753	73660852
ENSE00003666716	73650553	73650705
ENSE00003843533	73646581	73646626

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.89.

FANTOM5 (CAGE): breadth broad, TPM avg 46.3986 / max 3120.0683, expressed in 857 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115807	35.6158	825
115806	4.5821	295
115805	1.5637	133
115813	1.0889	123
115812	1.0502	107
115808	0.8608	202
115810	0.4155	90
115809	0.2296	107
115827	0.1858	72
115814	0.1760	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	99.89	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.89	gold quality
medulla oblongata	UBERON:0001896	99.82	gold quality
subthalamic nucleus	UBERON:0001906	99.80	gold quality
lateral globus pallidus	UBERON:0002476	99.79	gold quality
ventral tegmental area	UBERON:0002691	99.79	gold quality
superior vestibular nucleus	UBERON:0007227	99.79	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.77	gold quality
cranial nerve II	UBERON:0000941	99.75	gold quality
midbrain	UBERON:0001891	99.74	gold quality
substantia nigra	UBERON:0002038	99.74	gold quality
inferior olivary complex	UBERON:0002127	99.72	gold quality
hypothalamus	UBERON:0001898	99.68	gold quality
spinal cord	UBERON:0002240	99.66	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.60	gold quality
putamen	UBERON:0001874	99.59	gold quality
amygdala	UBERON:0001876	99.59	gold quality
olfactory bulb	UBERON:0002264	99.58	gold quality
pons	UBERON:0000988	99.56	gold quality
nucleus accumbens	UBERON:0001882	99.54	gold quality
substantia nigra pars compacta	UBERON:0001965	99.51	gold quality
globus pallidus	UBERON:0001875	99.40	gold quality
right frontal lobe	UBERON:0002810	99.34	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.31	gold quality
medial globus pallidus	UBERON:0002477	99.30	gold quality
corpus callosum	UBERON:0002336	99.29	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.16	gold quality
caudate nucleus	UBERON:0001873	99.13	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.11	gold quality
CA1 field of hippocampus	UBERON:0003881	99.09	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	1241.76
E-MTAB-7316	yes	44.78
E-HCAD-11	yes	25.35
E-MTAB-8410	yes	17.70
E-GEOD-135922	yes	16.33
E-GEOD-84465	yes	11.25
E-MTAB-5061	yes	9.95
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

76 targeting PLEKHB1, 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-1193	100.00	65.93	529
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4796-5P	99.34	70.06	810
HSA-MIR-5690	99.25	67.58	1012

Literature-anchored findings (GeneRIF, showing 3)

• Phr1 is widely and abundantly expressed throughout mature olfactory neurons and other primary sensory neurons, but its absence does not appear to affect olfactory morphology, regeneration, sensory function, or adaptation. (PMID:20301200)
• Rapid Wallerian degeneration requires the pro-degenerative molecules PHR1. (PMID:24840802)
• The human PHR1, a PH domain-containing protein with low expression in the heart and high expression in the brain, interacts with coxsackievirus B3 VP1, a major structural protein of coxsackievirus B3. (PMID:26318175)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	plekhb1	ENSDARG00000063519
mus_musculus	Plekhb1	ENSMUSG00000030701
rattus_norvegicus	Plekhb1	ENSRNOG00000018627

Paralogs (1): PLEKHB2 (ENSG00000115762)

Protein

Protein identifiers

Pleckstrin homology domain-containing family B member 1 — Q9UF11 (reviewed: Q9UF11)

Alternative names: Evectin-1, PH domain-containing protein in retina 1, Pleckstrin homology domain retinal protein 1

All UniProt accessions (12): Q9UF11, F5GY87, F5GY96, F5GYU9, F5GZ38, F5GZH3, F5H0R6, F5H114, F5H190, F5H1B8, F5H3M1, F5H866

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Homodimer. Interacts (via PH domain) with MYO1C. Interacts (via PH domain) with MYO7A. Binds transducins.

Subcellular location. Membrane. Cytoplasm.

Tissue specificity. Highly expressed in retina and brain. Levels are very low or not detectable in all other tissues tested.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UF11-1	1	yes
Q9UF11-2	2
Q9UF11-3	3
Q9UF11-4	4

RefSeq proteins (5): NP_001123505, NP_001123506, NP_001123507, NP_001123508, NP_067023* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR039680	PLEKHB1/2	Family

Pfam: PF00169

UniProt features (4 total): splice variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UF11-F1	64.84	0.21

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 190 (showing top): GCM_MAP4K4, LEE_NEURAL_CREST_STEM_CELL_DN, MORF_FLT1, MORF_MSH3, MORF_BRCA1, GOZGIT_ESR1_TARGETS_DN, MORF_ATRX, GOBP_PHOTOTRANSDUCTION, MORF_ESR1, MODULE_16, COLIN_PILOCYTIC_ASTROCYTOMA_VS_GLIOBLASTOMA_UP, chr11q13, MORF_RAD51L3, MODULE_66, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4

GO Biological Process (2): phototransduction (GO:0007602), regulation of cell differentiation (GO:0045595)

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

GO Cellular Component (2): cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
signal transduction	1
detection of light stimulus	1
cell differentiation	1
regulation of developmental process	1
regulation of cellular process	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

738 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLEKHB1	SELPLG	Q14242	667
PLEKHB1	CRX	O43186	649
PLEKHB1	SYNGR4	O95473	646
PLEKHB1	HECA	Q9UBI9	596
PLEKHB1	PLEK2	Q9NYT0	592
PLEKHB1	SELL	P14151	589
PLEKHB1	PLEK	P08567	542
PLEKHB1	TEX26	Q8N6G2	505
PLEKHB1	SELP	P16109	447
PLEKHB1	BOLA1	Q9Y3E2	427
PLEKHB1	TMEM210	A6NLX4	400
PLEKHB1	GPRC5B	Q9NZH0	395
PLEKHB1	MXD3	Q9BW11	386
PLEKHB1	SELE	P16111	380
PLEKHB1	PPT2	Q9UMR5	380

IntAct

30 interactions, top by confidence:

A	B	Type	Score
PLEKHB1	RAP1GDS1	psi-mi:“MI:0915”(physical association)	0.670
RAP1GDS1	PLEKHB1	psi-mi:“MI:0915”(physical association)	0.670
RAP1GDS1	DIRAS1	psi-mi:“MI:0914”(association)	0.640
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
PLEKHB1	CCR8	psi-mi:“MI:0915”(physical association)	0.370
ATXN1	PLEKHB1	psi-mi:“MI:0915”(physical association)	0.370
CTLA4	TMEM120B	psi-mi:“MI:0914”(association)	0.350
SIDT2	KLRG2	psi-mi:“MI:0914”(association)	0.350
AVPR1B	KLRG2	psi-mi:“MI:0914”(association)	0.350
TAS1R2	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
OR10H2	ABCD4	psi-mi:“MI:0914”(association)	0.350
RBFOX2	PRMT5	psi-mi:“MI:0914”(association)	0.350
OR10H1	NRP1	psi-mi:“MI:0914”(association)	0.350
TLCD5	TOM1L1	psi-mi:“MI:0914”(association)	0.350
FFAR1	SLC12A8	psi-mi:“MI:0914”(association)	0.350
KCNE3	TMEM131L	psi-mi:“MI:0914”(association)	0.350
GPR45	VWA8	psi-mi:“MI:0914”(association)	0.350
A4GALT	CLGN	psi-mi:“MI:0914”(association)	0.350
MFSD14A	FAM171A2	psi-mi:“MI:0914”(association)	0.350
NIPA1	UNC119B	psi-mi:“MI:0914”(association)	0.350
RBM11	PLEKHB1	psi-mi:“MI:0915”(physical association)	0.000
RUNX1	PLEKHB1	psi-mi:“MI:0915”(physical association)	0.000
LCOR	PLEKHB1	psi-mi:“MI:0915”(physical association)	0.000
DSCR9	PLEKHB1	psi-mi:“MI:0915”(physical association)	0.000
BTG3	PLEKHB1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (40): PLEKHB1 (Two-hybrid), PLEKHB1 (Two-hybrid), PLEKHB1 (Affinity Capture-Western), PLEKHB1 (Affinity Capture-MS), PLEKHB1 (Two-hybrid), SH2D2A (Affinity Capture-Luminescence), PLEKHB1 (Affinity Capture-MS), PLEKHB1 (Affinity Capture-MS), PLEKHB1 (Affinity Capture-MS), GLIS2 (Two-hybrid), RAP1GDS1 (Two-hybrid), VENTX (Two-hybrid), BAG3 (Two-hybrid), C10orf55 (Two-hybrid), PLEKHB1 (Two-hybrid)

ESM2 similar proteins: A0AV96, A2RUW1, B5X370, C1BZR1, F1M3L7, O35346, O42632, P34152, P87253, Q00078, Q00944, Q05397, Q08509, Q0E908, Q12929, Q292F9, Q2LGB5, Q3B8H2, Q3C2P8, Q4LBC7, Q4LBC8, Q4WVG0, Q5F3S2, Q5M7Y0, Q5R4H4, Q5R4K6, Q5R5P4, Q5R9H4, Q5RDN2, Q5Y171, Q5ZK05, Q61146, Q66H68, Q6DFR0, Q6INE3, Q7JUR6, Q7Z698, Q7ZV43, Q8R478, Q91738

Diamond homologs: Q5F3S2, Q5R4K6, Q96CS7, Q9QYE9, Q9QZC7, Q9UF11, Q9WU68

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1313 predictions. Top by Δscore:

Variant	Effect	Δscore
11:73650707:T:A	donor_loss	1.0000
11:73651779:T:TA	acceptor_gain	1.0000
11:73651783:TCCA:T	acceptor_loss	1.0000
11:73651784:CCAG:C	acceptor_loss	1.0000
11:73651785:CAG:C	acceptor_loss	1.0000
11:73651786:A:AG	acceptor_gain	1.0000
11:73651786:AG:A	acceptor_loss	1.0000
11:73651786:AGAT:A	acceptor_gain	1.0000
11:73651787:G:GC	acceptor_gain	1.0000
11:73651787:GA:G	acceptor_gain	1.0000
11:73651787:GAT:G	acceptor_gain	1.0000
11:73651787:GATG:G	acceptor_gain	1.0000
11:73651787:GATGT:G	acceptor_gain	1.0000
11:73651880:G:GT	donor_gain	1.0000
11:73651886:GCCCT:G	donor_gain	1.0000
11:73651887:CCCT:C	donor_gain	1.0000
11:73651887:CCCTG:C	donor_loss	1.0000
11:73651888:CCTG:C	donor_loss	1.0000
11:73651889:CTG:C	donor_loss	1.0000
11:73651890:TG:T	donor_loss	1.0000
11:73651891:G:GG	donor_gain	1.0000
11:73660751:A:AT	acceptor_loss	1.0000
11:73660752:GGTGC:G	acceptor_gain	1.0000
11:73660849:GCAG:G	donor_gain	1.0000
11:73660851:AGGT:A	donor_loss	1.0000
11:73660853:G:GG	donor_gain	1.0000
11:73660853:GT:G	donor_loss	1.0000
11:73660854:T:A	donor_loss	1.0000
11:73646383:G:T	donor_gain	0.9900
11:73649086:GA:G	donor_gain	0.9900

AlphaMissense

1558 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:73650570:T:A	W38R	1.000
11:73650570:T:C	W38R	1.000
11:73650571:G:C	W38S	0.999
11:73650572:G:C	W38C	0.999
11:73650572:G:T	W38C	0.999
11:73652979:T:A	W119R	0.999
11:73652979:T:C	W119R	0.999
11:73652981:G:C	W119C	0.999
11:73652981:G:T	W119C	0.999
11:73661553:C:A	A228D	0.999
11:73649082:G:C	R30T	0.998
11:73649083:A:C	R30S	0.998
11:73649083:A:T	R30S	0.998
11:73650571:G:T	W38L	0.998
11:73650585:T:C	F43L	0.998
11:73650587:T:A	F43L	0.998
11:73650587:T:G	F43L	0.998
11:73651827:T:C	L96P	0.998
11:73652980:G:C	W119S	0.998
11:73649076:T:C	L28P	0.997
11:73650586:T:C	F43S	0.997
11:73650592:T:C	L45P	0.997
11:73650604:G:T	G49V	0.997
11:73651863:T:C	L108P	0.997
11:73652992:T:C	L123P	0.997
11:73661550:C:A	A227D	0.997
11:73661559:G:A	G230E	0.997
11:73651863:T:A	L108H	0.996
11:73661547:G:A	G226E	0.996
11:73661565:C:A	A232E	0.996

dbSNP variants (sampled 300 via entrez): RS1000070921 (11:73662308 A>G), RS1000458325 (11:73655800 C>G,T), RS1001073779 (11:73660868 G>A), RS1001125254 (11:73654250 G>A), RS1001331057 (11:73646697 G>A), RS1001348931 (11:73655672 T>C), RS1001437604 (11:73652365 G>T), RS1001520324 (11:73654015 G>A,C), RS1001864505 (11:73647180 C>T), RS1001963028 (11:73657546 C>A), RS1002050014 (11:73659011 G>C), RS1002081287 (11:73659392 A>T), RS1002353021 (11:73657263 C>A), RS1002882247 (11:73645990 C>A,G,T), RS1003162155 (11:73651209 T>C)

Disease associations

OMIM: gene MIM:607651 | 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
GCST002726_12	Glucose homeostasis traits	6.000000e-06
GCST004494_4	Hand grip strength	1.000000e-06
GCST005760_4	Dimensional psychopathology (Cognitive)	2.000000e-07
GCST007327_25	Smoking status (ever vs never smokers)	3.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006830	insulin metabolic clearance rate measurement
EFO:0006941	grip strength measurement
EFO:0009098	cognitive domain measurement
EFO:0004318	smoking behavior

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	7
Benzo(a)pyrene	affects methylation, decreases expression	3
bisphenol A	affects cotreatment, increases methylation, affects expression	2
Lead	affects expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	increases expression	1
propionaldehyde	increases expression	1
beta-lapachone	decreases expression	1
1-nitropyrene	decreases expression	1
vanadyl sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
pentanal	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	increases expression	1
Air Pollutants	increases expression, increases abundance	1
Camptothecin	increases expression	1
Cisplatin	affects expression	1
Dactinomycin	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Fluorouracil	increases expression	1

Clinical trials (associated diseases)

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